76 results on '"Daftarian N"'
Search Results
2. Side-effects of iodized oil administration in patients with simple goiter
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Azizi, F. and Daftarian, N.
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- 2001
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3. A novel mutation and variable phenotypic expression in a large consanguineous pedigree with Jalili syndrome
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Rahimi-Aliabadi, S, primary, Daftarian, N, additional, Ahmadieh, H, additional, Emamalizadeh, B, additional, Jamshidi, J, additional, Tafakhori, A, additional, Ghaedi, H, additional, Noroozi, R, additional, Taghavi, S, additional, Ahmadifard, A, additional, Alehabib, E, additional, Andarva, M, additional, Shokraeian, P, additional, Atakhorrami, M, additional, and Darvish, H, additional
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- 2016
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4. Prevalence and risk factors of diabetes mellitus in a central district in Islamic Republic of Iran: a population-based study on adults aged 40-80 years
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Katibeh, M., primary, Hosseini, S., additional, Soleimanizad, R., additional, Manaviat, M.R., additional, Kheiri, B., additional, Khabazkhoob, M., additional, Daftarian, N., additional, and Dehghan, M.H., additional
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- 2015
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5. Pharmacologic treatment of wet type age-related macular degeneration; current and evolving therapies
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Shams Najafabadi H, Daftarian N, Ahmadieh H, and Zahra-Soheila Soheili
6. Novel mutations in TACSTD2 gene in families with gelatinous drop-like corneal dystrophy (GDLD)
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Alehabib, E., Javad Jamshidi, Ghaedi, H., Emamalizadeh, B., Andarva, M., Daftarian, N., Kanavi, M. R., Torbati, P. M., Espandar, G., Alinaghi, S., Johari, A. H., Saghally, M., Mohajerani, F., and Darvish, H.
7. Homozygous Mutation in TWNK Cases Ataxia, Sensorineural Hearing Loss and Optic Nerve Atrophy
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Jamali, F., Ghaedi, H., Tafakhori, A., Alehabib, E., Chapi, M., Daftarian, N., Darvish, H., and Javad Jamshidi
8. Survival and migration of bone marrow derived neurosphere after transplantation into subretinal space in albino rat amd model
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Kadkhodaeian, H. A., Tiraihi, T., Hamid Ahmadieh, Ziaiiardakani, H., Daftarian, N., and Taheri, T.
9. Polymeric Propranolol Nanoparticles for Intraocular Delivery: Formulation, Characterization, and Vitreous Pharmacokinetics.
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Chaharband F, Varshochian R, Dinarvand R, Sabbaghi H, Rezaei Kanavi M, Daftarian N, and Nourinia R
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Purpose: Recent studies have reported the promising effect of intravitreal propranolol on retinal neovascularization. However, rapid clearance and short half-life of the drug in the vitreous are the main drawbacks of this therapeutic approach. This study investigates the extension of the residence time of propranolol in the vitreous by polymeric nanoparticles (NPs) with the prospect of improving choroidal neovascularization treatment., Methods: The poly (lactic-co-glycolic) acid (PLGA) NPs were fabricated by a modified double emulsion solvent evaporation method and the obtained NPs were characterized for their size, poly dispersity index (PDI), and surface image. The in vitro release, cell cytotoxicity, and uptake of NPs were also evaluated. To investigate the effect of the vitreous pharmacokinetic drug loaded NPs versus that of the free propranolol, they were intravitreally injected into the rabbits' eyes and the drug vitreous concentrations in defined intervals were analyzed by high performance liquid chromatography (HPLC)., Results: The spherical NPs with about 230 nm size, and almost 10% drug loading were obtained. Based on the 3-(4, 5-Dimethylthiazol-2-Yl)-2, 5-Diphenyltetrazolium Bromide (MTT) outcomes, 30 µg/ml of propranolol was considered as the guide dosage in the intravitreal injection. Confocal microscopy images verified the presence of labeled NPs in the posterior segment after five days of receiving the injection. In vivo assay revealed that the vanishing rate of propranolol in rabbits treated with propranolol NPs was reduced at twice the rate as compared to that of the vanishing rate experienced with only the free drug., Conclusion: PLGA NPs can prolong the existence of propranolol in both vitreous and posterior ocular tissues, and thus, may provide an effective approach in treatment of posterior segment neovascularization., (Copyright © 2024 Chaharband et al.)
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- 2024
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10. Modification of a Selective NTRK2 Agonist and Confirmation of Activity in a Glaucoma-on-a-Chip Model.
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Nafian F, Yazdani S, Javad Rasaee M, Kamali Doust Azad B, Daftarian N, and Rezaei Kanavi M
- Abstract
Purpose: RNYK is a selective agonist of the neurotrophic tyrosine kinase receptor type 2 (NTRK2) which has been screened from a phage-displayed peptide library. Its sequence is SGVYKVAYDWQH, similar to a native NTRK2 ligand, that is, brain-derived neurotrophic factor (BDNF). The current study was performed to recognize and confirm critical residues for RNYK activity in a glaucoma-on-a-chip model., Methods: We designed a modified RNYK (mRNYK) peptide based on hotspots of the RNYK sequence identified by alanine scanning. The critical residues consisted of tyrosine, valine, aspartic acid, and tryptophan (YVDW); however, lysine and glutamine were also maintained in the final sequence (YKVDWQ) for forming amide bonds and peptide dimerization. The affinity of mRNYK binding was confirmed by testing against NTRK2 receptors on the surface of ATRA-treated SH-SY5Y cells. The neuroprotective effect of mRNYK was also evaluated in cell culture after elevated pressure insult in a glaucoma-on-a-chip model., Results: The primary amine on the lysine side-chain from one sequence (YKVDWQ) reacted with a γ-carboxamide group of glutamine from the other sequence, forming dimeric mRNYK. In silico , molecular dynamic simulations of the mRNYK-NTRK2 complex showed more stable and stronger interactions as compared to the RNYK-NTRK2 complex. In vitro , mRNYK demonstrated a neuroprotective effect on SH-SY5Y cells under normal and elevated pressure comparable to RNYK. The 50% effective concentration (logEC50) for mRNYK was 0.7009, which was better than RNYK with a logEC50 of 0.8318., Conclusion: The modified peptide studied herein showed improved stability over the original peptide (RNYK) and demonstrated potential for use as a BDNF agonist with neuroprotective properties for treatment of neurodegenerative disorders such as glaucoma., Competing Interests: None., (Copyright © 2024 Nafian et al.)
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- 2024
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11. Vision-related quality of life in patients with retinal vein occlusion.
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Ramin S, Rostami F, Ahmadieh H, Daftarian N, Nourinia R, Abbasi A, Kheiri B, Sabbaghi H, and Sheibani K
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- Humans, Middle Aged, Aged, Eye Pain, Surveys and Questionnaires, Quality of Life, Retinal Vein Occlusion diagnosis
- Abstract
Purpose: This study aims to assess the vision-related quality of life in patients with retinal vein occlusion (RVO) among those referred to Labbafinejad Medical Center and Imam Hossein Hospital between 2019 and 2021., Methods: This comparative study included 37 eligible patients diagnosed with various types of RVO, with an average age of 61 ± 9. To ensure data validity, we included 74 age- and sex-matched healthy individuals. Only cases with a definitive diagnosis of RVO, confirmed by two retina specialists (ND and RN), were included. We assessed the vision-related quality of life of our participants using the National Eye Institute Visual Functioning Questionnaire-25 (NEI-VFQ-25). All participants underwent interviews., Results: In our study, we examined the vision-related quality of life in different subgroups of RVO patients. Overall, RVO patients had a significantly lower total VRQoL score compared to healthy individuals (P < 0.001), except in the subscale analysis of specific factors such as ocular pain, color vision, and driving, where no statistically significant difference was observed. A statistically significant difference was found in the comparison of subgroups, indicating lower VRQoL in central retinal vein occlusion (CRVO) patients (P = 0.010). Furthermore, a significant correlation was observed between lower VRQoL and decreased vision (P = 0.009) as well as longer disease duration (P = 0.011)., Conclusion: Retinal vein occlusion can significantly reduce vision-related quality of life, particularly in more severe cases., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
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- 2024
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12. A health terminological system for inherited retinal diseases: Content coverage evaluation and a proposed classification.
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Sabbaghi H, Madani S, Ahmadieh H, Daftarian N, Suri F, Khorrami F, Saviz P, Shahriari MH, Motevasseli T, Fekri S, Nourinia R, Moradian S, and Sheikhtaheri A
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- Humans, Cross-Sectional Studies, Unified Medical Language System, International Classification of Diseases, Systematized Nomenclature of Medicine, Retinal Diseases diagnosis, Retinal Diseases genetics
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Purpose: To present a classification of inherited retinal diseases (IRDs) and evaluate its content coverage in comparison with common standard terminology systems., Methods: In this comparative cross-sectional study, a panel of subject matter experts annotated a list of IRDs based on a comprehensive review of the literature. Then, they leveraged clinical terminologies from various reference sets including Unified Medical Language System (UMLS), Online Mendelian Inheritance in Man (OMIM), International Classification of Diseases (ICD-11), Systematized Nomenclature of Medicine (SNOMED-CT) and Orphanet Rare Disease Ontology (ORDO)., Results: Initially, we generated a hierarchical classification of 62 IRD diagnosis concepts in six categories. Subsequently, the classification was extended to 164 IRD diagnoses after adding concepts from various standard terminologies. Finally, 158 concepts were selected to be classified into six categories and genetic subtypes of 412 cases were added to the related concepts. UMLS has the greatest content coverage of 90.51% followed respectively by SNOMED-CT (83.54%), ORDO (81.01%), OMIM (60.76%), and ICD-11 (60.13%). There were 53 IRD concepts (33.54%) that were covered by all five investigated systems. However, 2.53% of the IRD concepts in our classification were not covered by any of the standard terminologies., Conclusions: This comprehensive classification system was established to organize IRD diseases based on phenotypic and genotypic specifications. It could potentially be used for IRD clinical documentation purposes and could also be considered a preliminary step forward to developing a more robust standard ontology for IRDs or updating available standard terminologies. In comparison, the greatest content coverage of our proposed classification was related to the UMLS Metathesaurus., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sabbaghi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
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13. Choroidal structure investigated by choroidal vascularity index in patients with inherited retinal diseases.
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Bayat K, Hassanpour K, Sabbaghi H, Fekri S, Daftarian N, Motevasseli T, Suri F, Kheiri B, Yaseri M, and Ahmadieh H
- Abstract
Purpose: To evaluate the choroidal structure in patients with inherited retinal diseases (IRDs) by investigating the choroidal vascularity index (CVI)., Methods: The present study was conducted on 113 IRD patients and 113 sex- and age-matched healthy individuals. Patients' data was extracted from the Iranian National Registry for IRDs (IRDReg®). Total choroidal area (TCA) was determined between retinal pigment epithelium and choroid-scleral junction,1500 microns on either side of the fovea. Luminal area (LA) was considered as the black area corresponding to the choroidal vascular spaces, following Niblack binarization. CVI was calculated as the ratio of the LA to the TCA. CVI and other parameters were compared among different types of IRD and the control group., Results: The IRD diagnosis included retinitis pigmentosa (n = 69), cone-rod dystrophy (n = 15), Usher syndrome (n = 15), Leber congenital amaurosis (n = 9), and Stargardt disease (n = 5). Sixty-one (54.0%) individuals of each of the study and control groups were male. The average CVI was 0.65 ± 0.06 in the IRD patients and 0.70 ± 0.06 in the control group (P < 0.001). Accordingly, the average of TCA and LA were 2.32 ± 0.63 and 1.52 ± 0.44 mm [1] in patients with IRDs, respectively. The measurements for the TCA and the LA were significantly lower in all subtypes of IRD (P-values < 0.05)., Conclusion: CVI is significantly lower in patients with IRD than in healthy age-matched individuals. Choroidal changes in IRDs may be related to the changes in the lumen of the choroidal vessels rather than the stromal changes., (© 2023. The Author(s).)
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- 2023
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14. Effect of Music During General Anesthesia on Anesthetic Consumption During Vitrectomy Surgery.
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Tajbakhsh A, Salimi S, Daftarian N, and Abtahi D
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Background: Controversy remains about the positive role of music during general anesthesia and postoperative recovery. We, therefore, tested the hypothesis that intraoperative exposure to classical music reduces the propofol necessary to maintain the bispectral index (BIS) close to 50 during vitrectomy surgery., Materials and Methods: This double-blind clinical study is evaluating 50 patients undergoing vitrectomy surgery under general anesthesia. Patients were randomly assigned to music and white noise groups, and relevant sounds were played to patients after induction of anesthesia. The two groups were compared for the use of propofol as an anesthetic to maintain a BIS near 50 and for postoperative pain, anxiety, nausea, and vomiting., Results: Propofol consumption to maintain the set BIS score was much lower in the music group than in the white noise group (78.72 ± 25.76 microgram/kg/min and 117.91 ± 36.78 microgram/kg/min, respectively, P -value = 0.000). Postoperative pain scores were also much lower in the music group than in the white noise group ( P -value = 0.000) and anxiety levels between these two groups did not differ ( P -value = 0.870). No patient in the music group had complaints of postoperative nausea and vomiting (PONV) compared to six patients in the white noise group ( P -value = 0.011)., Conclusions: Listening to music during general anesthesia for vitrectomy surgery can reduce the use of anesthetics, postoperative pain, and PONV. Further, controlled studies are necessary to confirm our results., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Advanced Biomedical Research.)
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- 2023
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15. Risk of Arrhythmia Among New Users of Hydroxychloroquine in Rheumatoid Arthritis and Systemic Lupus Erythematosus: A Population-Based Study.
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Hoque MR, Lu L, Daftarian N, Esdaile JM, Xie H, and Aviña-Zubieta JA
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- Humans, Hydroxychloroquine adverse effects, British Columbia epidemiology, Antirheumatic Agents adverse effects, Atrial Fibrillation drug therapy, Atrial Fibrillation epidemiology, Lupus Erythematosus, Systemic drug therapy, Lupus Erythematosus, Systemic epidemiology, Arthritis, Rheumatoid drug therapy, Arthritis, Rheumatoid epidemiology
- Abstract
Objectives: We assessed the association between hydroxychloroquine (HCQ) initiation and risk of arrhythmia among patients with incident rheumatoid arthritis (RA) or with incident systemic lupus erythematosus (SLE)., Methods: All patients with incident RA or SLE and no arrhythmic events, not receiving antiarrhythmic medications, and not receiving HCQ prior to the index date of disease in British Columbia, Canada, between January 1996 and December 2014 were identified from administrative databases. We identified patients who were dispensed HCQ prescriptions (HCQ initiators) or were not dispensed HCQ prescriptions (HCQ noninitiators) during each study year; groups were matched 1:1 by propensity scores using baseline confounders on demographics, comorbidities, medications, and health care utilization. Outcomes were any new arrhythmias, atrial fibrillation, abnormal electrocardiograms, including long QT syndrome and conduction disorder, and other unspecified arrhythmias during follow-up. We used cause-specific Cox proportional hazards models with death as a competing event to assess the association between HCQ initiation and the outcomes., Results: We identified 11,518 propensity score-matched patients with RA or SLE in each group. Over the mean follow-up of 8 years, there were 1,610 and 1,646 incident arrhythmias in the HCQ initiator group and the noninitiator group, respectively, with crude incidence rates of arrhythmia of 17.5 and 18.1 in 1,000 persons per year, respectively. The adjusted cause-specific hazard ratio (cHR) for patients who received HCQ was 0.96 (95% confidence interval [95% CI] 0.89-1.03) compared with HCQ noninitiators, and the cHRs for patients who took HCQ and had arrhythmia subtypes of atrial fibrillation, abnormal electrocardiograms, and other unspecified arrhythmias were 0.93 (95% CI 0.83-1.04), 0.98 (95% CI 0.87-1.11), and 0.95 (95% CI 0.84-1.07), respectively., Conclusion: Risk of any type of arrhythmia was not increased among new users of HCQ., (© 2022 American College of Rheumatology.)
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- 2023
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16. The Inhibitory Effect of Connective Tissue Growth Factor Antibody on Postoperative Fibrosis in a Rabbit Model of Trabeculectomy.
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Hassanpour K, Kanavi MR, Daftarian N, Samaeili A, Suri F, Pakravan M, Doozandeh A, Aski SA, Fakhri M, Moghaddasi A, Ahmadieh H, and Esfandiari H
- Abstract
Purpose: To compare the efficacy of subconjunctival injection of an anti-connective tissue growth factor antibody (anti-CTGF) versus mitomycin-C (MMC) and placebo in reducing scar formation in a rabbit model of trabeculectomy., Methods: A total of 14 rabbits were included. Nine rabbits underwent trabeculectomy with subconjunctival injections of either anti-CTGF antibody, MMC, or balanced salt solution (BSS), each administered in three eyes, before peritomy. The anti-CTGF group received a repeated dose of the antibody five days after surgery. All nine rabbits were euthanized on day 14; the globes were stained with hematoxylin & eosin, Masson's Trichrome, and immunohistochemistry for detecting alpha-smooth muscle (α-SMA) actin. RNA extraction was performed on five eyes of the remaining rabbits which included one eye without any surgery, one eye 5 hr after trabeculectomy without any injection, one eye five days after trabeculectomy without any injection, and two eyes five days after trabeculectomy with administration of MMC and BSS, respectively., Results: The mean bleb area in the anti-CTGF, MMC, and control groups was 3.8 ± 1.45, 5.9 ± 1.4, and 3.5 ± 1.9 mm
2 , respectively. Collagenous tissue was found to occupy the bleb area by 13.7%, 13.5%, and 18.5%, respectively. This ratio was significantly higher in the BSS group ( P = 0.04). The expression of CTGF mRNA after 5 hr and five days in eyes undergoing trabeculectomy were significantly more pronounced as compared to the unoperated eye. The mean H-SCORE of α-SMA-immune reactive cells calculated as the grade of staining multiplied by the percentage of immune stained cells was 14.6, 10.22, and 140.58 in the anti-CTGF, MMC, and control groups, respectively. While the control eyes had a significantly higher score ( P s < 0.001), the anti-CTGF and MMC groups were comparable ( P = 0.87)., Conclusion: Based on the results of this animal study, the anti-CTGF antibody injection resulted in a significant reduction in collagenous tissue and myofibroblast cells after trabeculectomy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Hassanpour et al.)- Published
- 2022
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17. Vision-Related Quality of Life in Patients with Inherited Retinal Dystrophies.
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Shojaei S, Sabbaghi H, Mehrabi Y, Daftarian N, Etemad K, and Ahmadieh H
- Abstract
Purpose: To evaluate the effect of inherited retinal dystrophies (IRDs) on vision-related quality of life (VRQoL) among IRDs' patients in Iran., Methods: This cross-sectional study was conducted on 192 patients with different types of IRDs who were randomly selected from registered patients in the Iranian National Registry for Inherited Retinal Dystrophy (IRDReg®). All ophthalmic findings were collected based on the recorded data in IRDReg®. Moreover, the eligible participants were interviewed to fill out the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) to assess their VRQoL. Ordinal logistic regression was used to evaluate the possible association of the different clinical and nonclinical factors such as demographic information, socioeconomic status, and visual function with VRQoL., Results: The overall mean of a composite score of VRQoL was 45. All subscales obtained from the NEI VFQ-25 questionnaire except general health, mental health, and ocular pain had a significant negative correlation with logMAR best corrected visual acuity (BCVA) and near visual acuity variables. There was a statistically significant relationship between VRQoL and factors like age (odds ratio [OR] = 0.91, 95% confidence interval [CI]: 0.87-0.94), employment status (OR = 1.37, 95% CI: 1.05-4.74), logMAR BCVA (OR = 0.31, 95% CI: 0.19-0.49) and normal color vision (OR = 1.92, 95% CI: 1.74-5.01)., Conclusion: The VRQoL of patients with IRDs in this study was low. BCVA could be an indicator to show VRQoL., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Current Ophthalmology.)
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- 2022
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18. Application of a Mapping Method in the Analysis of Electroretinogram in Patients with Retinitis Pigmentosa.
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Bakhshi S, Behbahani S, and Daftarian N
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- Electroretinography methods, Humans, Retina, Retinal Diseases, Retinitis Pigmentosa diagnosis, Retinitis Pigmentosa genetics
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Purpose: Retinitis pigmentosa (RP) is a group of degenerative retinal diseases characterized by mutations in genes affecting retinal pigment epithelium (RPE) function, as well as mutations directly involving photoreceptors. This paper aims to evaluate a nonlinear method to distinguish between the RP and normal eye based on the Electroretinogram (ERG) signal., Method: ERG signal was recorded from 28 eyes of patients with the RP and 32 normal eyes. The ERG signal consists of four different stimuli, including two dark-adapted and two light-adapted stimuli. The time-domain analysis includes the amplitude and implicit time to consider the robustness of the nonlinear method. A parabolic mapping method was performed, and two criteria (Theta angle and density) extracted from the parabola were compared for both groups., Results: The results showed that a-wave's amplitude and implicit time significantly changed in the dark- and light-adapted stimuli. The amplitude of the b-wave showed significant changes in all stimuli. However, the implicit time of b-wave had a significant increase only in the dark-adapted 3.0 ERG. Both nonlinear criteria showed significant changes in the RP group for all the stimuli. The p -values of dark-adapted 3.0 ( p = .0121), dark-adapted 10.0 ( p = .0014), light-adapted 3.0 ( p = .0119), and flicker 30 Hz ( p = .0323) showed significant differences. Using the density criterion, the statistical test demonstrated a significant difference between the RP and healthy normal group in dark-adapted 3.0 ( p = .0076), dark-adapted 10.0 ( p = .0024), light-adapted 3.0 ( p = .0021), and flicker 30 Hz ( p = .0165)., Conclusion: The proposed features have made it possible to distinguish between healthy and RP eyes. This method might be helpful in early diagnosis.
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- 2022
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19. Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment.
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Bahena P, Daftarian N, Maroofian R, Linares P, Villalobos D, Mirrahimi M, Rad A, Doll J, Hofrichter MAH, Koparir A, Röder T, Han S, Sabbaghi H, Ahmadieh H, Behboudi H, Villanueva-Mendoza C, Cortés-Gonzalez V, Zamora-Ortiz R, Kohl S, Kuehlewein L, Darvish H, Alehabib E, Arenas-Sordo ML, Suri F, Vona B, and Haaf T
- Subjects
- Humans, Iran, Mutation, Pedigree, Phenotype, Retinal Degeneration genetics, Usher Syndromes diagnosis, Usher Syndromes genetics
- Abstract
Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is clinically and genetically heterogeneous. Moreover, several conditions with phenotypes overlapping Usher syndrome have been described. This makes the molecular diagnosis of hereditary deaf-blindness challenging. Here, we performed exome sequencing and analysis on 7 Mexican and 52 Iranian probands with combined retinal degeneration and hearing impairment (without intellectual disability). Clinical assessment involved ophthalmological examination and hearing loss questionnaire. Usher syndrome, most frequently due to biallelic variants in MYO7A (USH1B in 16 probands), USH2A (17 probands), and ADGRV1 (USH2C in 7 probands), was diagnosed in 44 of 59 (75%) unrelated probands. Almost half of the identified variants were novel. Nine of 59 (15%) probands displayed other genetic entities with dual sensory impairment, including Alström syndrome (3 patients), cone-rod dystrophy and hearing loss 1 (2 probands), and Heimler syndrome (1 patient). Unexpected findings included one proband each with Scheie syndrome, coenzyme Q10 deficiency, and pseudoxanthoma elasticum. In four probands, including three Usher cases, dual sensory impairment was either modified/aggravated or caused by variants in distinct genes associated with retinal degeneration and/or hearing loss. The overall diagnostic yield of whole exome analysis in our deaf-blind cohort was 92%. Two (3%) probands were partially solved and only 3 (5%) remained without any molecular diagnosis. In many cases, the molecular diagnosis is important to guide genetic counseling, to support prognostic outcomes and decisions with currently available and evolving treatment modalities., (© 2021. The Author(s).)
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- 2022
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20. Identification of three novel homozygous variants in COL9A3 causing autosomal recessive Stickler syndrome.
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Rad A, Najafi M, Suri F, Abedini S, Loum S, Karimiani EG, Daftarian N, Murphy D, Doosti M, Moghaddasi A, Ahmadieh H, Sabbaghi H, Rajati M, Hashemi N, Vona B, and Schmidts M
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- Genes, Recessive genetics, Humans, Mutation genetics, Pedigree, Phenotype, Arthritis diagnosis, Arthritis genetics, Collagen Type IX genetics, Connective Tissue Diseases genetics, Connective Tissue Diseases pathology, Hearing Loss, Sensorineural genetics, Osteochondrodysplasias genetics, Retinal Detachment diagnosis, Retinal Detachment genetics, Retinal Detachment pathology
- Abstract
Background: Stickler syndrome (STL) is a rare, clinically and molecularly heterogeneous connective tissue disorder. Pathogenic variants occurring in a variety of genes cause STL, mainly inherited in an autosomal dominant fashion. Autosomal recessive STL is ultra-rare with only four families with biallelic COL9A3 variants reported to date., Results: Here, we report three unrelated families clinically diagnosed with STL carrying different novel biallelic loss of function variants in COL9A3. Further, we have collected COL9A3 genotype-phenotype associations from the literature., Conclusion: Our report substantially expands the molecular genetics and clinical basis of autosomal recessive STL and provides an overview about allelic COL9A3 disorders., (© 2022. The Author(s).)
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- 2022
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21. RetINal Toxicity And HydroxyChloroquine Therapy (INTACT): protocol for a prospective population-based cohort study.
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Daftarian N, Lima A, Marozoff S, Ojo D, Levasseur SD, Maberley DAL, Hoens A, Esdaile J, Dawes M, Aviña-Zubieta JA, Adante B, Bhui RD, Bhui SB, Butler M, Chui L, Erasmus M, Etminan M, Godinho D, Hay E, Hollands H, Hoonjan M, Joe A, Lukaris A, Mammo Z, Navajas E, Pakzad-Vaezi K, Sanmugasunderam S, and Shojania K
- Subjects
- Adult, British Columbia epidemiology, Cohort Studies, Humans, Hydroxychloroquine adverse effects, Prospective Studies, Tomography, Optical Coherence, Antirheumatic Agents adverse effects, Arthritis, Rheumatoid chemically induced, Arthritis, Rheumatoid drug therapy, Lupus Erythematosus, Systemic drug therapy, Retinal Diseases chemically induced, Retinal Diseases diagnosis, Retinal Diseases epidemiology
- Abstract
Purpose: Hydroxychloroquine (HCQ) is an important medication for patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and other rheumatic diseases. Although it is well-tolerated and cost-effective, the risk of HCQ retinal toxicity is of increasing concern. The aim of this study is to re-examine the HCQ retinal toxicity incidence rate, risk factors and clinical course after discontinuation., Methods: We designed a prospective population-based cohort study in adult patients with SLE or RA, currently receiving HCQ for five or more years, who are residents of British Columbia (BC), Canada. Based on administrative data, we identified 5508 eligible participants (1346 SLE and 4162 RA). They will participate in annual or biannual retinal screening over 5 years in alignment with the recently revised American Academy of Ophthalmology guidelines. To standardise procedures for retinal screening, imaging, diagnostic criteria, severity staging and data transfer, a consensus meeting was convened in December 2019 with participation of BC retinal specialists and the research team. Agreement was attained on: use of spectral domain-optical coherence tomography as the primary objective screening modality; classification of images into categories of normal, equivocal or abnormal; and transferring the equivocal and abnormal images plus corresponding subjective test results via cloud-based server from each clinic to a reading centre. Confirmation of HCQ retinal toxicity diagnoses and severity staging will be performed by three independent and masked reviewers. The incidence of HCQ retinal toxicity will be calculated, accounting for the competing risk of death. Hazard ratios for each risk factor will be calculated for the risk of HCQ retinopathy, after adjusting for confounders. We will also estimate the risk of HCQ retinal toxicity progression over 5 years., Ethics and Dissemination: This study has received approval from the University of British Columbia Clinical Research Ethics Board (H20-00736) and the Vancouver Coastal Health Research Institute., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2022
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22. Mutation Screening of Six Exons of ABCA4 in Iranian Stargardt Disease Patients.
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Darbari E, Ahmadieh H, Daftarian N, Rezaei Kanavi M, Suri F, Sabbaghi H, and Elahi E
- Abstract
Purpose: Stargardt disease type 1 (STGD1) is a recessively inherited retinal disorder that can cause severe visual impairment. ABCA4 mutations are the usual cause of STGD1. ABCA4 codes a transporter protein exclusively expressed in retinal photoreceptor cells. The genecontains 50 exons. Mutations are most frequent in exons 3, 6, 12, and 13, and exons 10 and 42 each contain two common variations. We aimed to screen these exons for mutations in Iranian STGD1 patients., Methods: Eighteen STGD1 patients were recruited for genetic analysis. Diagnosis by retina specialists was based on standard criteria, including accumulation of lipofuscin. The six ABCA4 exons were PCR amplified and sequenced by the Sanger method., Results: One or more ABCA4 -mutated alleles were identified in 5 of the 18 patients (27.8%). Five different mutations including two splice site (c.1356+1G > A and c.5836-2A > G) and three missense mutations (p.Gly1961Glu, p.Gly1961Arg, and p.Gly550Arg) were found. The p.Gly1961Glu mutation was the only mutation observed in two patients., Conclusion: As ABCA4 mutations in exons 6, 12, 10, and 42 were identified in approximately 25% of the patients studied, these may be appropriate exons for screening projects. As in other populations, STDG1 causative ABCA4 mutations are heterogeneous among Iranian patients, and p.Gly1961Glu may be relatively frequent., Competing Interests: There are no conflicts of interest., (Copyright © 2022 Darbari et al.)
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- 2022
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23. New criteria for evaluation of electroretinogram in patients with retinitis pigmentosa.
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Sabbaghi H, Behbahani S, Daftarian N, and Ahmadieh H
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- Healthy Volunteers, Humans, Retina, Electroretinography, Retinitis Pigmentosa diagnosis
- Abstract
Background: Electroretinogram (ERG) plays an essential role in the diagnosis of retinal disease. Choosing appropriate methods could extract valuable information from ERG. In this study, a new criterion based on time-frequency domain analysis was proposed to investigate the retina in retinitis pigmentosa (RP) patients., Materials and Methods: The total number of 16 eyes from eight RP patients and 20 eyes from age-matched healthy subjects were assessed. The signals included photopic and scotopic ERGs. Continuous wavelet transform was applied to ERGs. Dominant frequencies were extracted, and the contours related to these dominant frequencies were selected. As a new criterion, the areas related to dominant frequency contours were considered a feature to differentiate the RP and normal groups. To better evaluate the proposed criterion results, the time-domain analysis characteristics of ERG were also considered., Results: The results showed an increase in implicit time and reduced amplitude in RP patients (P < 0.05). A significant decrease of dominant frequencies and increasing their occurrence time were seen in ERG of RP patients. Also, in RP patients, the third dominant frequency was disappeared from the three main frequencies observed in photopic ERGs of normal subjects. The area criterion showed a significant decrease in RP groups (P < 0.05)., Conclusion: RP can cause changes in the time and time-frequency components of the ERG. The area index could represent a new view of the characteristics of the ERG in the time-frequency domain. This criterion can help the ophthalmologist to have a better evaluation of retinal disease., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2021
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24. Retinal Vascular Abnormalities in Different Types of Inherited Retinal Dystrophies Assessed by Optical Coherence Tomography Angiography.
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Sabbaghi H, Daftarian N, Hassanpour K, Fekri S, Nourinia R, Suri F, Kheiri B, Yaseri M, Rajabpour M, Sheibani K, and Ahmadieh H
- Abstract
Purpose: To investigate the retinal vascular characteristics among patients with different types of inherited retinal dystrophies (IRDs)., Methods: This comparative cross-sectional study was conducted on 59 genetically confirmed cases of IRD including 37 patients with retinitis pigmentosa (RP) (74 eyes), 13 patients with Stargardt disease (STGD) (26 eyes), and 9 patients with cone-rod dystrophy (CRD) (18 eyes). Both eyes of 50 age- and sex-matched healthy individuals were investigated as controls. All participants underwent optical coherence tomography angiography to investigate the vascular densities (VDs) of superficial and deep capillary plexus (SCP and DCP) as well as foveal avascular zone area., Results: In RP, significantly lower VD in whole image ( P = 0.001 for DCP), fovea ( P = 0.038 for SCP), parafovea ( P < 0.001 for SCP and DCP), and perifovea ( P < 0.001 for SCP and DCP) was observed compared to controls. In STGD, VD of parafovea ( P = 0.012 for SCP and P = 0.001 for DCP) and fovea ( P = 0.016 for DCP) was significantly lower than controls. In CRD, the VD of parafovea ( P = 0.025 for DCP) was significantly lower than controls. Whole image density was significantly lower in RP compared to STGD ( P < 0.001 for SCP) and CRD ( P = 0.037 for SCP). VD in parafovea ( P = 0.005 for SCP) and perifovea ( P < 0.001 for SCP and DCP) regions was significantly lower in RP compared with STGD. Also, foveal VD in STGD was significantly lower than RP ( P = 0.023 for DCP)., Conclusion: Our study demonstrated lower VDs in three different IRDs including RP, STGD, and CRD compared to healthy controls. Changes were more dominant in RP patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Current Ophthalmology.)
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- 2021
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25. Intravitreal connective tissue growth factor neutralizing antibody or bevacizumab alone or in combination for prevention of proliferative vitreoretinopathy in an experimental model.
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Daftarian N, Baigy O, Suri F, Kanavi MR, Balagholi S, Afsar Aski S, Moghaddasi A, Nourinia R, Abtahi SH, and Ahmadieh H
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- Adult, Angiogenesis Inhibitors administration & dosage, Animals, Cells, Cultured, Connective Tissue Growth Factor immunology, Disease Models, Animal, Drug Therapy, Combination, Female, Humans, Immunohistochemistry, Intravitreal Injections, Male, Middle Aged, Rabbits, Retinal Pigment Epithelium metabolism, Retinal Pigment Epithelium pathology, Treatment Outcome, Vascular Endothelial Growth Factor A antagonists & inhibitors, Vitreoretinopathy, Proliferative diagnosis, Vitreoretinopathy, Proliferative metabolism, Antibodies, Neutralizing administration & dosage, Bevacizumab administration & dosage, Connective Tissue Growth Factor administration & dosage, Retinal Pigment Epithelium drug effects, Vitreoretinopathy, Proliferative prevention & control
- Abstract
Connective tissue growth factor (CTGF) is released by retinal pigment epithelial (RPE) cells and detectable in proliferative membranes (PrMs). This experimental study was performed to investigate the mRNA and protein levels of both CTGF and vascular endothelial growth factor A (VEGF-A) in a rabbit model of proliferative vitreoretinopathy (PVR). In addition, the effects of a single intravitreal injection of the safe dose of anti-CTGF or bevacizumab as monotherapy and in combination were evaluated. PVR was induced in the right eye of albino rabbits by intravitreal injection of cultured adult human RPE cells. Quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot analysis of CTGF and VEGF-A were performed on whole eye tissue in the PVR model versus controls at different time points. In the next step, the PVR models were assigned to five groups. The monotherapy groups received a single intravitreal injection of 0.1 ml of anti-CTGF 100 μg/ml (final concentration of 6.6 μg/ml in the vitreous) or 0.03 ml of 25 mg/ml bevacizumab. In the combined group, the abovementioned amounts of anti-CTGF and bevacizumab were injected intravitreally from separate sites in one session. No antibody injection was performed in the control group. Intravitreal injection of 0.1 ml of control IgG (1 mg/ml of isotype matched) antibody was performed in the placebo group. After 2 weeks, histologic evaluation including, trichrome staining for collagen, immunostaining by anti-alpha-smooth muscle actin for myofibroblasts, and anti-collagen type-1 antibody on paraffin embedded anterior-posterior sections was done. In addition, fundus photography was performed for clinically equivalent PVR staging. Twenty-four hours following PVR induction, CTGF mRNA and protein levels increased five- and- three-fold compared to controls, respectively (P < 0.001). VEGF-A mRNA and protein levels decreased significantly after 72 h of PVR induction compared to controls (P < 0.05). Means of PrM thickness and myofibroblast cell counts significantly decreased in the anti-CTGF group (P < 0.001 and P < 0.05, respectively). The mean area of collagen type-1 fibers of PrM in the mono- and combination therapy groups that received intravitreal anti-CTGF was significantly reduced (P < 0.001); in addition, mild PVR (stage-1 and 2) formation occurred in comparison with moderate to severe PVR (stage-4 and higher) in other groups. In conclusion, we found that intravitreal injection of CTGF neutralizing antibody resulted in a reduction in PrM thickness, collagen fibers and myofibroblast density in the PVR model. CTGF inhibition may represent a potential therapeutic target for PVR., (Copyright © 2021. Published by Elsevier Ltd.)
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- 2021
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26. Autosomal Recessive Bestrophinopathy: Clinical and Genetic Characteristics of Twenty-Four Cases.
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Khojasteh H, Azarmina M, Ebrahimiadib N, Daftarian N, Riazi-Esfahani H, Naraghi H, Sabbaghi H, Khodabande A, Faghihi H, Moghaddasi A, Bazvand F, Manaviat MR, Ahmadieh H, Hassanpoor N, and Suri F
- Abstract
Background: To describe ocular manifestations, imaging characteristics, and genetic test results of autosomal recessive bestrophinopathy (ARB). The study design is an observational case series., Methods: Forty-eight eyes of 24 patients diagnosed with ARB underwent complete ophthalmic examinations including refraction, anterior and posterior segment examination, enhanced depth imaging optical coherence tomography (EDI-OCT), fluorescein angiography (FA), electroretinography (ERG), and electrooculography (EOG). Optical coherence tomography angiography (OCTA) and BEST1 gene sequencing were performed in selected patients., Results: The age at onset was 4-35 years (mean: 18.6 years). The male-to-female ratio was 0.45. All patients were hyperopic, except one with less than one diopter myopia. EOG was abnormal in 18 cases with near-normal ERGs. Six patients did not undergo EOG due to their young age. Eighteen patients (75%) had a thick choroid on EDI-OCT, of which three had advanced angle-closure glaucoma, 15 patients were hyperopic, and eight of them had more than four diopters hyperopia in both eyes. Macular retinoschisis was observed in 46 eyes of 23 patients (95%) with cysts mostly located in the inner nuclear layer (INL) to the outer nuclear layer (ONL). Of the 18 patients who underwent FA, mild peripheral leakage was seen in eight eyes of four patients (22%). Subfoveal choroidal neovascularization (CNV) was seen in three eyes of two patients (6%) that responded well to intravitreal bevacizumab (IVB). Seven mutations of the bestrophin-1 (BEST1) gene were found in this study; however, only two of them (p.Gly34 = and p.Leu319Pro) had been previously reported as the cause of ARB based on ClinVar and other literature studies., Conclusions: ARB can be presented with a wide spectrum of ocular abnormalities that may not be easily diagnosed. Pachychoroid can occur alongside retinal schisis and may be the underlying cause of angle-closure glaucoma in ARB. Our study also expands the pathogenic mutation spectrum of the BEST1 gene associated with ARB., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Hassan Khojasteh et al.)
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- 2021
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27. A lab-on-a-chip model of glaucoma.
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Nafian F, Kamali Doust Azad B, Yazdani S, Rasaee MJ, and Daftarian N
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- Animals, Brain-Derived Neurotrophic Factor, Intraocular Pressure, Rats, Rats, Wistar, Retinal Ganglion Cells, Glaucoma drug therapy, Lab-On-A-Chip Devices
- Abstract
Aims: We developed a glaucoma-on-a-chip model to evaluate the viability of retinal ganglion cells (RGCs) against high pressure and the potential effect of neuroprotection., Methods: A three-layered chip consisting of interconnecting microchannels and culture wells was designed and fabricated from poly-methyl methacrylate sheets. The bottom surface of the wells was modified by air plasma and coated with different membranes to provide a suitable extracellular microenvironment. RGCs were purified from postnatal Wistar rats by magnetic assisted cell sorting up to 70% and characterized by flow cytometry and immunocytochemistry. The cultured RGCs were exposed to normal (15 mmHg) or elevated pressure (33 mmHg) for 6, 12, 24, 36, and 48 hr, with and without adding brain-derived neurotrophic factor (BDNF) or a novel BDNF mimetic (RNYK)., Results: Multiple inlet ports allow culture media and gas into the wells under elevated hydrostatic pressure. PDL/laminin formed the best supporting membrane. RGC survival rates were 85%, 78%, 70%, 67%, and 61% under normal pressure versus 40%, 22%, 18%, 12%, and 10% under high pressure at 6, 12, 24, 36, and 48 hr, respectively. BDNF and RNYK separately reduced RGC death rates about twofold under both normal and elevated pressures., Conclusion: This model recapitulated the effects of elevated pressure over relatively short time periods and demonstrated the neuroprotective effects of BDNF and RNYK., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)
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- 2020
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28. Choroidal Thickness in Different Types of Inherited Retinal Dystrophies.
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Sabbaghi H, Ahmadieh H, Jalili J, Behnaz N, Fakhri M, Suri F, Kheiri B, Rajabpour M, Entezari M, and Daftarian N
- Abstract
Purpose: To compare the choroidal thickness among eyes with retinitis pigmentosa (RP), Stargardt disease, Usher syndrome, cone-rod dystrophy, and healthy eyes of sex- and age-matched individuals., Methods: In this comparative study, 503 eyes with RP ( n = 264), cone-rod dystrophy ( n = 109), Stargardt disease ( n = 76), and Usher syndrome ( n = 54) were included. To validate the data, 109 healthy eyes of 56 sex- and age-matched individuals were studied as controls. Choroidal imaging was performed using enhanced depth imaging-optical coherence tomography. Choroidal thickness was measured manually using MATLAB software at 13 points in nasal and temporal directions from the foveal center with the interval of 500 µm and the choroidal area encompassing the measured points was calculated automatically., Results: The mean age was 36.33 ± 13.07 years (range, 5 to 72 years). The mean choroidal thickness at 13 points of the control eyes was statistically significantly higher than that in eyes with RP ( P < 0.001) and Usher syndrome ( P < 0.05), but not significantly different from that in eyes with Stargardt disease and cone-rod dystrophy. Among different inherited retinal dystrophies (IRDs), the choroidal thickness was the lowest in eyes with RP ( P < 0.001). Choroidal thickness in the subfoveal area correlated negatively with best-corrected visual acuity ( r = - 0.264, P < 0.001) and the duration of ocular symptoms ( r = - 0.341, P < 0.001) in all studied IRDs. No significant correlation was observed between the subfoveal choroidal thickness and central macular thickness ( r = - 0.24, P = 0.576)., Conclusion: Choroidal thinning in four different types of IRDs does not follow a similar pattern and depends on the type of IRD and the duration of ocular symptoms. A larger cohort is required to verify these findings., Competing Interests: There are no conflicts of interest., (Copyright © 2020 Sabbaghi et al.)
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- 2020
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29. The First Inherited Retinal Disease Registry in Iran: Research Protocol and Results of a Pilot Study.
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Sabbaghi H, Daftarian N, Suri F, Mirrahimi M, Madani S, Sheikhtaheri A, Khorrami F, Saviz P, Zarei Nejad M, Tivay A, Shahriari HA, Maleki A, Ahmadi SS, Sargazi M, Cremers FPM, Najafi M, Vona B, Haaf T, Bahena-Carbajal P, Moghadasi A, Naraghi H, Yaseri M, Kheiri B, Kalantarion M, Sabbaghi E, Salami M, Pazooki L, Zendedel K, Mojarrab S, and Ahmadieh H
- Subjects
- Adolescent, Adult, Aged, Child, Child, Preschool, Community-Based Participatory Research, Female, Humans, Infant, Iran epidemiology, Male, Middle Aged, Pilot Projects, Proof of Concept Study, Registries, Retinal Diseases epidemiology, Web Browser, Young Adult, Access to Information, Genetic Testing, Retinal Diseases diagnosis, Retinal Diseases genetics
- Abstract
Background: To describe the protocol for developing a national inherited retinal disease (IRD) registry in Iran and present its initial report., Methods: This community-based participatory research was approved by the Ministry of Health and Medical Education of Iran in 2016. To provide the minimum data set (MDS), several focus group meetings were held. The final MDS was handed over to an engineering team to develop a web-based software. In the pilot phase, the software was set up in two referral centers in Iran. Final IRD diagnosis was made based on clinical manifestations and genetic findings. Ultimately, patient registration was done based on all clinical and non-clinical manifestations., Results: Initially, a total of 151 data elements were approved with Delphi technique. The registry software went live at www. IRDReg.org based on DHIS2 open source license agreement since February 2016. So far, a total of 1001 patients have been registered with a mean age of 32.41±15.60 years (range, 3 months to 74 years). The majority of the registered patients had retinitis pigmentosa (42%, 95% CI: 38.9% to 45%). Genetic testing was done for approximately 20% of the registered individuals., Conclusion: Our study shows successful web-based software design and data collection as a proof of concept for the first IRD registry in Iran. Multicenter integration of the IRD registry in medical centers throughout the country is well underway as planned. These data will assist researchers to rapidly access information about the distribution and genetic patterns of this disease., (© 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)
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- 2020
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30. Peripheral blood CD163(+) monocytes and soluble CD163 in dry and neovascular age-related macular degeneration.
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Daftarian N, Zandi S, Piryaie G, Nikougoftar Zarif M, Ranaei Pirmardan E, Yamaguchi M, Behzadian Nejad Q, Hasanpour H, Samiei S, Pfister IB, Soheili ZS, Nakao S, Barakat A, Garweg JG, Ahmadieh H, and Hafezi-Moghadam A
- Subjects
- Aged, Angiogenesis Inhibitors pharmacology, Animals, Cell Differentiation drug effects, Cell Differentiation physiology, Choroidal Neovascularization blood, Choroidal Neovascularization metabolism, Female, Humans, Macrophages drug effects, Macrophages metabolism, Male, Mice, Mice, Inbred C57BL, Monocytes drug effects, Retina drug effects, Retina metabolism, Vascular Endothelial Growth Factor A metabolism, Visual Acuity drug effects, Visual Acuity physiology, Wet Macular Degeneration drug therapy, Antigens, CD blood, Antigens, CD metabolism, Antigens, Differentiation, Myelomonocytic blood, Antigens, Differentiation, Myelomonocytic metabolism, Monocytes metabolism, Receptors, Cell Surface blood, Receptors, Cell Surface metabolism, Wet Macular Degeneration blood, Wet Macular Degeneration metabolism
- Abstract
Macrophages are the main infiltrating immune cells in choroidal neovascularization (CNV), a hallmark of the human wet, or neovascular age-related macular degeneration (AMD). Due to their plasticity and ability to adapt to the local microenvironment in a tissue-dependent manner, macrophages display polar functional phenotypes characterized by their cell surface markers and their cytokine profiles. We found accumulation of hemoglobin-scavenging cluster of differentiation 163 (CD163)(+) macrophages in laser-induced CNV lesions and higher expression of CD163(+) monocytes in the peripheral blood on day 7 post injury in mice. In comparison, CD80(+) macrophages did not differ with laser-injury in young or aged mice and did not significantly change in the peripheral blood of CNV mice. We examined the percentages of CD163(+), CD206(+), and CD80(+) monocytes in the peripheral blood of patients with wet AMD, patients with dry AMD, and in age-matched individuals without AMD as controls. Percentages of peripheral blood CD163(+) monocytes in both dry AMD (P < .001) and wet AMD (P < .05) were higher than in age-matched non-AMD controls, while there was no difference between the groups in the percentages of peripheral CD206(+) and CD80(+) monocytes. Further, serum level of soluble CD163 (sCD163) was elevated only in patients with wet AMD (P < .05). An examination of 40 cytokine levels across the study groups revealed that anti-VEGF treated patients with wet AMD, who showed no exudative signs on the day of blood drawing had a cytokine profile that was similar to that of non-AMD individuals. These results indicate that CD163 could be further evaluated for its potential as a useful marker of disease activity in patients with neovascular AMD. Future studies will address the origin and potential mechanistic role of CD163(+) macrophages in wet AMD pathologies of angiogenesis and leakage of blood components., (© 2020 Federation of American Societies for Experimental Biology.)
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- 2020
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31. Trimethyl chitosan-hyaluronic acid nano-polyplexes for intravitreal VEGFR-2 siRNA delivery: Formulation and in vivo efficacy evaluation.
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Chaharband F, Daftarian N, Kanavi MR, Varshochian R, Hajiramezanali M, Norouzi P, Arefian E, Atyabi F, and Dinarvand R
- Subjects
- Chitosan chemistry, Choroidal Neovascularization genetics, Choroidal Neovascularization pathology, Drug Compounding, Drug Delivery Systems, Human Umbilical Vein Endothelial Cells, Humans, Hyaluronic Acid chemistry, Hyaluronic Acid pharmacology, Intravitreal Injections, RNA, Small Interfering chemistry, RNA, Small Interfering genetics, Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors, Chitosan pharmacology, Choroidal Neovascularization drug therapy, RNA, Small Interfering pharmacology, Vascular Endothelial Growth Factor Receptor-2 genetics
- Abstract
As vascular endothelial growth factor in choroidal neovascularization is a major cause of visual loss of the elderlies and diabetics, gene therapy may offer an alternative treatment. However, siRNA instability and inefficient delivery are the main hindrances. To address this issue, we developed a nano-sized siRNA loaded therapeutic delivery system. The chitosan-hyaluronic acid nano-polyplexes were prepared by the modified ionic gelation method. The obtained nano-polyplex with a narrow size distribution, indicated no significant cytotoxicity in the MTT test and proper cellular uptake in confocal images. The RT-PCR analysis indicated remarkable gene silencing on HUVEC cells. The intravitreally administered nano-polyplexes in rabbits overcame both the vitreous and retina barriers and reached the posterior tissues efficiently. Intravitreal injections of the VEGFR-2 siRNA nano-polyplexes significantly reduced the size of the laser-induced choroidal neovascularization, compared to the control group. Consequently, the developed formulation can be a promising candidate for intravitreal delivery of siRNA., (Copyright © 2020 Elsevier Inc. All rights reserved.)
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- 2020
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32. PRPF31 reduction causes mis-splicing of the phototransduction genes in human organotypic retinal culture.
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Azizzadeh Pormehr L, Ahmadian S, Daftarian N, Mousavi SA, and Shafiezadeh M
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- Carrier Proteins genetics, Carrier Proteins metabolism, Cells, Cultured, Eye Proteins metabolism, Humans, Microfilament Proteins genetics, Microfilament Proteins metabolism, Mutation, Retina cytology, Ribonucleoproteins genetics, Ribonucleoproteins metabolism, Tetraspanins genetics, Tetraspanins metabolism, Transducin genetics, Transducin metabolism, Eye Proteins genetics, RNA Splicing, Retina metabolism, Retinitis Pigmentosa genetics
- Abstract
PRPF31 is ubiquitously expressed splicing factor and has an essential role in the pre-mRNA splicing in all tissues. However, it is not clear how reduced expression of this general splicing factor leads to retinal restricted disease, retinitis pigmentosa (RP). In this study, we used RNA interference and RNA-sequencing to mimic the PRPF31 haploinsufficiency in human organotypic retinal cultures (HORCs). We examined the effects of PRPF31 deficiency on splicing by analyzing the differential exon usages (DEUs) and intron retentions of the retinal transcriptome. Our results revealed that the PRPF31 deficiency causes mis-splicing of genes involved in RNA processing (PRPF3, PRPF8, PRPF4, and PRPF19) and phototransduction (RHO, ROM1, FSCN2, GNAT2, and GNAT1) in the retina in the PRPF31 reduced samples. Mis-splicing of genes implicated in phototransduction was associated with photoreceptor degeneration observed in RP patients. Our data revealed that PRPF31 deficiency leads to the mis-splicing of a distinct subset of pre-mRNAs with a widespread effect on phototransduction and RNA processing.
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- 2020
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33. Homozygous Mutation in TWNK Cases Ataxia, Sensorineural Hearing Loss and Optic Nerve Atrophy.
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Jamali F, Ghaedi H, Tafakhori A, Alehabib E, Chapi M, Daftarian N, Darvish H, and Jamshidi J
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- Adolescent, Hearing Loss, Sensorineural etiology, Humans, Iran, Male, Mutation, Optic Atrophy, Autosomal Dominant etiology, Exome Sequencing, DNA Helicases, Mitochondrial Proteins, Spinocerebellar Degenerations genetics
- Abstract
The TWNK (C10orf2) gene encodes Twinkle, an essential helicase for mtDNA replication. Homozygous mutations in TWNK can lead to mitochondrial DNA depletion syndrome 7 (MTDPS7) that usually manifests as Infantile onset spinocerebellar ataxia (IOSCA). Here, we report a 15-year-old Iranian boy with three main symptoms; ataxia, sensorineural hearing loss and optic nerves atrophy which were accompanied by other symptoms including flexion contracture, dysarthric speech, nystagmus, dystonia and borderline intellectual disability. Whole exome sequencing (WES) revealed a homozygous mutation in his TWNK gene. The mutation was a transversion which replaced a C with A (NM_021830.4 (TWNK):c.874C>A). This nucleotide substitution results in replacing a Threonine with Proline in codon 292 of Twinkle protein (p.Pro292Thr). In silico analyses showed that this amino acid change in Twinkle could be deleterious and disease-causing; therefore, we attribute the symptoms of our patient to this mutation. Our study extended the homozygous mutation spectrum of the TWNK gene that leads to IOSCA., (© 2019 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)
- Published
- 2019
34. Combination of intravitreal bevacizumab and erythropoietin versus intravitreal bevacizumab alone for refractory diabetic macular edema: a randomized double-blind clinical trial.
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Entezari M, Flavarjani ZK, Ramezani A, Nikkhah H, Karimi S, Moghadam HF, Daftarian N, and Yaseri M
- Subjects
- Aged, Angiogenesis Inhibitors administration & dosage, Diabetic Retinopathy complications, Diabetic Retinopathy diagnosis, Double-Blind Method, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Intravitreal Injections, Macula Lutea pathology, Macular Edema diagnosis, Macular Edema etiology, Male, Middle Aged, Tomography, Optical Coherence methods, Treatment Outcome, Vascular Endothelial Growth Factor A antagonists & inhibitors, Bevacizumab administration & dosage, Diabetic Retinopathy drug therapy, Erythropoietin administration & dosage, Macular Edema drug therapy
- Abstract
Purpose: To evaluate the effect of three intravitreal bevacizumab (IVB) injections alone or in combination with intravitreal erythropoietin (EPO) in the treatment of refractory diabetic macular edema (DME)., Methods: In a randomized double-blind clinical trial, 48 eyes of 34 diabetic patients with refractory DME were enrolled. Eyes were randomly assigned to receive either 3 monthly injections of 0.05 cc (1.25 mg) IVB plus 0.05 cc (1000 unit) EPO or 0.05 cc (1.25 mg) IVB alone. Main outcome was best-corrected visual acuity (BCVA) changes and secondary outcome was central macular thickness (CMT). The patients were followed for 6 months., Results: Mean BCVA changes up to 4 and 6 months were insignificant in both groups. It changed from 0.72 ± 0.56 logMAR at baseline to 0.74 ± 0.5 (P = 0.85) and 0.71 ± 0.44 (P = 0.40) in the combination group and from 0.48 ± 0.39 logMAR to 0.47 ± 0.35 (P = 0.48) and 0.52 ± 0.33 (P = 0.69) in the IVB alone group, at 4 and 6 months, respectively. The difference of mean BCVA changes between the groups was insignificant at both 4 and 6 months (P = 0.07 and P = 0.36, respectively). Within the group changes of mean CMT were significant only in the combination group at 4 and 6 months, from 518 ± 134 μ at baseline to 472 ± 151 to 475 ± 167 μ, respectively (P = 0.01 and P = 0.05). Corresponding changes were not significant in the IVB alone group. However, the difference between the groups was not significant at all visits (P = 0.51 and P = 0.71, respectively)., Conclusions: This clinical trial demonstrated that intravitreal erythropoietin had no additional effect to IVB in the treatment of refractory DME in the short term., Trial Registration: Clinical trials.gov identifier: NCT03821168.
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- 2019
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35. PRPH2 mutation as the cause of various clinical manifestations in a family affected with inherited retinal dystrophy.
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Daftarian N, Mirrahimi M, Sabbaghi H, Moghadasi A, Zal N, Dehghan Banadaki H, Ahmadieh H, and Suri F
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- Adult, Aged, Female, Fluorescein Angiography, Follow-Up Studies, Fundus Oculi, Humans, Male, Pedigree, Phenotype, Prognosis, Retinal Dystrophies pathology, Eye Proteins genetics, Inheritance Patterns genetics, Mutation, Peripherins genetics, Retinal Dystrophies etiology
- Abstract
Background/Objectives : To reveal the underlying genetic defect in a complex family affected with different clinical features of inherited retinal dystrophy, we carried out whole exome sequencing followed by confirmatory molecular tests. Materials and Methods : Complete ophthalmic examinations were performed for available affected family members. Whole exome sequencing, bioinformatics analysis, Sanger sequencing confirmation, and segregation analysis were done to identify the causative mutation. Results : Clinical findings suggested fundus flavimaculatus as an early clinical feature progressing to an extensive chorioretinal atrophy involving the macula and mid-periphery of the fundus in one parent and central areolar chorioretinal dystrophy (CACD) as the most probable clinical diagnosis in another parent. Macular pattern dystrophy for one of their daughters and a Leber congenital amaurosis (LCA) like phenotype for the daughter with an early onset retinal dystrophy (EORD) phenotype was suggested. We found a known pathogenic nonsense variation in the PRPH2 gene (NM_000322: p.Gln239Ter). The parents with end stage fundus flavimaculatus and CACD diagnosis and their daughter with macular pattern dystrophy were heterozygous for the identified variant. The daughter affected with EORD/LCA like retinal dystrophy was homozygous for the same variation. Conclusions : In this family, the same pathogenic variant in PRPH2 gene showed a wide range of clinical features of extensive chorioretinal macular atrophy with flecks as fundus falvimaculatus to CACD and macular pattern dystrophy in the heterozygous inheritance pattern and early onset/LCA like retinal dystrophy in the patient who was homozygous for the causative variant.
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- 2019
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36. Incidence and risk factors of retinopathy of prematurity and utility of the national screening criteria in a tertiary center in Iran.
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Khorshidifar M, Nikkhah H, Ramezani A, Entezari M, Daftarian N, Norouzi H, Shahiari M, Radfar M, Norinia R, and Karimi S
- Abstract
Aim: To determine the incidence and risk factors of retinopathy of prematurity (ROP) and the sensitivity of current screening criteria in a tertiary eye center in Tehran, Iran., Methods: In a cross-sectional observational study, neonates weighing ≤2000 grams at birth or born <34wk gestational age (GA) and all other infants at risk of ROP admitted to the neonatal intensive care unit (NICU) or referred to our ROP clinic were investigated. The incidence of ROP and severe ROP ( i.e. patients needing treatment) were determined. The associations between risk factors and the development and severity of ROP were assessed. We also examined the sensitivity of the current national screening guideline in Iran., Results: Among 207 infants, the incidence of ROP and severe ROP was 33.3% and 11.1%, respectively. Mean GA and birth weight (BW) were significantly lower in ROP vs non-ROP infants (29±2wk vs 33±3wk, P <0.001; 1274±489 g vs 1916±550 g, P <0.001, respectively). Univariate analysis displayed significant association between ROP incidence and GA, BW, NICU admission period, blood transfusion, surfactant usage, sepsis, intraventricular hemorrhage and patent ductus arteriosus ( P <0.05 for all). BW [relative risk (RR): 0.857 (0.711-0.873), P <0.001], GA [RR: 0.788 (0.711-0.873), P <0.001] and blood transfusion [RR: 1.888 (0.995-3.583), P =0.052] were independent ROP risk factors. The sensitivity of country-specific screening guidelines was 95.7% and 100% for overall and severe ROP detection, respectively., Conclusion: ROP incidence is relatively high in Iran. Identifying ROP risk factors results in more accurate screening and reduces the risk of irreversible vision loss. The ROP screening criteria utilized in Iran are efficient at the present time.
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- 2019
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37. Effects of intravitreal connective tissue growth factor neutralizing antibody on choroidal neovascular membrane-associated subretinal fibrosis.
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Daftarian N, Rohani S, Kanavi MR, Suri F, Mirrahimi M, Hafezi-Moghadam A, Soheili ZS, and Ahmadieh H
- Subjects
- Angiogenesis Inhibitors therapeutic use, Animals, Bevacizumab therapeutic use, Choroidal Neovascularization pathology, Connective Tissue Growth Factor antagonists & inhibitors, Disease Models, Animal, Fibrosis pathology, Intravitreal Injections, Rats, Vascular Endothelial Growth Factor A antagonists & inhibitors, Antibodies, Neutralizing pharmacology, Choroidal Neovascularization metabolism, Connective Tissue Growth Factor metabolism
- Abstract
Connective tissue growth factor (CTGF) plays an essential role in the regulation of extracellular matrix proteins and pro-fibrotic and angiogenic factors. This experimental research was conducted to evaluate if CTGF is elevated after induction of a choroidal neovascular membrane (CNVM) and whether intravitreal anti-CTGF without and with intravitreal bevacizumab (IVB) may have any effect on the CNVM associated sub-retinal fibrosis. In adherence to ARRIVE guidelines, CNVM was induced by laser spots in the right eye retinas of ninety-four pigmented rats. Quantitative real-time reverse transcription PCR (qRT-PCR) and western-blot analysis were performed on sclerochoroidal tissues of forty-four rats before and at different time intervals after laser application. The remaining fifty rats were randomly divided into five groups after laser application. Group A received intravitreal injection of 2 μl of the 50 μg/ml anti-CTGF. In group B, intravitreal injection of 2 μl of 25 mg/ml bevacizumab was performed. Group C received 1 μl intravitreal anti-CTGF and 1 μl IVB. Group D did not receive any intravitreal injection as the control group. In group E, intravitreal injection of 2 μl of nonspecific purified mouse IgG antibody was performed as the placebo group. After two weeks, double immunohistochemistry was performed by isolectin B4 and anti-collagen type1 on the sclerochoroidal flat-mounts. Masked measurement of the fluorescent images of the CNVM and CNVM associated sub-retinal fibrosis areas was performed using the image J software. Ctgf mRNA and CTGF protein levels increased to the maximum level in 24 h after laser application and remained higher than the control level up to the 14th day for the Ctgf mRNA and up to the 7th day for the CTGF protein level. Means of CNVM associated sub-retinal fibrosis areas in three treatment groups (A, B and C) were significantly less than the control (D) and placebo (E) groups (P < 0.001, <0.05, <0.001 respectively). For groups A and C, mean CNVM associated sub-retinal fibrosis areas were also significantly less than group B (P < 0.05 and < 0.01, respectively). In conclusion, this study showed significant reduction of the CNVM associated sub-retinal fibrosis via inhibition of the CTGF which mediates the final steps of fibrosis in various inflammatory and angiogenic pathways., (Copyright © 2019. Published by Elsevier Ltd.)
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- 2019
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38. Incomplete penetrance of CRX gene for autosomal dominant form of cone-rod dystrophy.
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Chapi M, Sabbaghi H, Suri F, Alehabib E, Rahimi-Aliabadi S, Jamali F, Jamshidi J, Emamalizadeh B, Darvish H, Mirrahimi M, Ahmadieh H, and Daftarian N
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Female, Humans, Male, Middle Aged, Pedigree, Penetrance, Phenotype, Visual Acuity, Exome Sequencing, Young Adult, Cone-Rod Dystrophies genetics, Cone-Rod Dystrophies pathology, Genes, Dominant, Homeodomain Proteins genetics, Polymorphism, Single Nucleotide, Trans-Activators genetics
- Abstract
Purpose : Cone-rod dystrophy (CRD) is an inherited retinal dystrophy that is transmitted via different modes of inheritance. Mutations in more than 30 genes have been identified to cause the disease. We aimed to investigate the genetic agents of two unrelated cone-rod dystrophy affected Iranian families with autosomal recessive inheritance patterns. Methods : Whole-exome sequencing (WES) was performed for identification of the disease-causing mutations in the probands of both families. The candidate mutations were further confirmed by Sanger sequencing. Samples from five available members of each family were then sequenced for the mutations present in the probands. Comprehensive ocular examinations for all members of the families carrying the mutations were completed by ophthalmologists. Results : We identified a novel premature stop codon c.310C>T in CRX gene in heterozygote form in two symptomatic and two non-symptomatic members of one family (family-A), and a known CRX mutation c.122G>A in homozygote form in another (family B). c.122G>A has been reported to cause late-onset autosomal dominant form of the disease in previous studies. However, the middle-aged heterozygous carriers of the mutation in this family showed normal phenotype. Conclusion : The CRX gene has been previously linked to the autosomal dominant form of cone-rod dystrophy. We report incomplete penetrance of CRX gene for autosomal dominant form of the disease. Incomplete penetrance of the mutations may be partly caused by the influence of other genes in the complex genetic network underlying retinal regulation.
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- 2019
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39. Generation of Retinal Pigmented Epithelium-Like Cells from Pigmented Spheres Differentiated from Bone Marrow Stromal Cell-Derived Neurospheres.
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Aboutaleb Kadkhodaeian H, Tiraihi T, Ahmadieh H, Ziaei H, Daftarian N, and Taheri T
- Subjects
- Animals, Carrier Proteins genetics, Carrier Proteins metabolism, Cell Transdifferentiation, Iran, Male, Mesenchymal Stem Cells cytology, Nestin, Osteogenesis, Otx Transcription Factors genetics, Otx Transcription Factors metabolism, Phagocytosis, Rats, Retinal Degeneration metabolism, Retinal Pigment Epithelium cytology, cis-trans-Isomerases genetics, cis-trans-Isomerases metabolism, Cell Differentiation physiology, Mesenchymal Stem Cells metabolism, Retinal Pigment Epithelium metabolism
- Abstract
Background: Retinal degeneration causes blindness, and cell replacement is a potential therapy. The purpose of this study is to formation of pigmented neurospheres in a simple medium, low-cost, high-performance manner over a short period of time while expressing markers of RPE cells and the activation of specific genes of the pigment cells. Also, these neurospheres have the ability to produce a monolayer of retinal pigment epithelium-like cells (RPELC) with the ability of photoreceptor outer segment phagocytosis., Methods: BMSC were isolated from pigmented hooded male rats and were immunoreactive to BMSC markers, then converted into neurospheres, differentiated into pigmented spheres (PS), and characterized using Retinal pigment epithelium-specific 65 kDa protein (RPE65), Retinaldehyde-binding protein 1 (CRALBP) and orthodenticle homeobox 2 (OTX2) markers by immunocytochemistry, RT-PCR and RT-qPCR. The PS were harvested into RPELC. The functionality of RPELC was evaluated by phagocytosis of fluorescein-labeled photoreceptor outer segment., Results: The BMSC immunophenotype was confirmed by immunostained for fibronectin, CD90, CD166 and CD44. These cells differentiated into osteogenic and lipogenic cells. The generated neurospheres were immunoreactive to nestin and stemness genes. The PS after 7-14 days were positive for RPE65 (92.76-100%), CRALBP (95.21-100%) and OTX2 (94.88-100%), and after 30 days RT-PCR, qPCR revealed increasing in gene expression. The PS formed a single layer of RPELC after cultivation and phagocyte photoreceptor outer segments., Conclusion: Bone marrow stromal stem cells can differentiate into functional retinal pigmented epithelium cells in a simple, low-cost, high-performance manner over a short period of time. These cells due to expressing the RPELC genes and markers can be used in cell replacement therapy for degenerative diseases including age-related macular degeneration as well as retinitis pigmentosa., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest.
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- 2019
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40. Peptide selected by phage display increases survival of SH-SY5Y neurons comparable to brain-derived neurotrophic factor.
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Nafian F, Rasaee MJ, Yazdani S, Daftarian N, Soheili ZS, and Kamali Doust Azad B
- Abstract
Brain-derived neurotrophic factor (BDNF) is a well-known neuroprotectant and a potent therapeutic candidate for neurodegenerative diseases. However, there are several clinical concerns about its therapeutic applications. In the current study, we designed and developed BDNF-mimicking small peptides as an alternative to circumvent these problems. A phage-displayed peptide library was screened using BDNF receptor (neurotrophic tyrosine kinase receptor type2 [NTRK2]) and evaluated by ELISA. The peptide sequences showed similarity to loop2 of BDNF, they were recognized as discontinuous epitopes though. Interestingly, in silico molecular docking showed strong interactions between the peptide three-dimensional models and the surface residues of the NTRK2 protein at the IgC2 domain. A consensus peptide sequence was then synthesized to generate a mimetic construct (named as RNYK). The affinity binding and function of this construct was confirmed by testing against the native structure of NTRK2 in SH-SY5Y cells in vitro using flow-cytometry and MTT assays, respectively. RNYK at 5 ng/mL prevented neuronal degeneration of all- trans-retinoic acid-treated SH-SY5Y with equal efficacy to or even better than BDNF at 50 ng/mL., (© 2018 Wiley Periodicals, Inc.)
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- 2019
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41. Modeling a Telemedicine Screening Program for Diabetic Retinopathy in Iran and Implementing a Pilot Project in Tehran Suburb.
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Safi S, Ahmadieh H, Katibeh M, Yaseri M, Nikkhah H, Karimi S, Nourinia R, Tivay A, Zareinejad M, Azarmina M, Ramezani A, Moradian S, Dehghan MH, Daftarian N, Abbasi D, Eshghi Fallah A, and Kheiri B
- Abstract
Purpose: To model a community-based telescreening program for diabetic retinopathy (DR) in Iran and to implement a pilot project at the Iranian Diabetes Society (IDS) branch in a Tehran suburb., Methods: In this mixed model study, a web application called the "Iranian Retinopathy Teleophthalmology Screening (IRTOS)" was launched. The educational course for DR screening was established for general practitioners (GPs). Registered patients in IDS branch were recalled for fundus photography; images were transferred to the reading center via IRTOS to be graded by GPs, and patients were informed about the results via mobile messaging. All images were independently reviewed by a retina specialist as the gold standard. Patients who required further assessment were referred to an eye hospital., Results: Overall, 604 subjects with diabetes were screened; of these, 50% required referral. The sensitivity and specificity for diagnosis of any stage of DR by trained GPs were 82.8% and 86.2%, respectively, in comparison to the gold standard. The corresponding values for detecting any stage of diabetic macular edema (DME) were 63.5% and 96.6%, respectively., Conclusions: Telescreening was an effective method for detecting DR in a Tehran suburb. This screening model demonstrated its capacity for promoting diabetic eye care services at the national level. However, the sensitivity for detecting DME needs to be improved by modifying the referral pathway and promoting the skill of GPs.
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- 2019
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42. In Vivo Evaluation of PAX6 Overexpression and NMDA Cytotoxicity to Stimulate Proliferation in the Mouse Retina.
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Ranaei Pirmardan E, Soheili ZS, Samiei S, Ahmadieh H, Mowla SJ, Naseri M, and Daftarian N
- Subjects
- Animals, Cell Cycle drug effects, Cell Death drug effects, Cell Differentiation drug effects, Cell Line, HEK293 Cells, Humans, Ki-67 Antigen metabolism, Mice, Models, Animal, Retinal Degeneration metabolism, Retinal Ganglion Cells drug effects, Retinal Ganglion Cells metabolism, Cell Proliferation drug effects, N-Methylaspartate pharmacology, PAX6 Transcription Factor metabolism, Retina drug effects, Retina metabolism
- Abstract
Retinal degenerative diseases, due to the lack of regeneration systems and self-renewable cells, often lead to visual impairment. Pax6 is a pleiotropic transcription factor and its expression level determines self-renewal status or differentiation of retinal cells. Here, we investigated the fate of simultaneous induction of retinal ganglion cell death and Pax6 overexpression in retro-differentiation of retinal cells and their commitment to re-enter into the cell cycle. Induction of acute retinal ganglion cell death and generation of mouse experimental model was performed by N-methyl D-aspartic acid (NMDA) injection. Recombinant AAV2 virus harboring PAX6 cDNA and reporter gene was injected into untreated and model mouse eyes. Histological analyses, including IHC and retinal flatmounts immunostaining were performed. The number of Ki67+ cells was clearly increased in model mice, presumably due to NMDA treatment and regardless of Pax6 over-expression. Unlike previous studies, Ki67+ cells were found in GCL layer and interestingly ONL cells expressed Sox2 stemness marker after NMDA cytotoxicity. The potential of retinal cells for robust Ki67 expression, after injury, and expression of Sox2, confirmed their intrinsic plasticity and made a vivid prospect for retinal regenerative medicine.
- Published
- 2018
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43. COL18A1 is a candidate eye iridocorneal angle-closure gene in humans.
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Suri F, Yazdani S, Chapi M, Safari I, Rasooli P, Daftarian N, Jafarinasab MR, Ghasemi Firouzabadi S, Alehabib E, Darvish H, Klotzle B, Fan JB, Turk C, and Elahi E
- Subjects
- Adult, Aged, Aged, 80 and over, Collagen Type VIII genetics, Collagen Type XVIII genetics, DNA Mutational Analysis, Eye metabolism, Female, Glaucoma, Angle-Closure metabolism, Humans, Male, Middle Aged, Pedigree, Collagen Type VIII metabolism, Collagen Type XVIII metabolism, Glaucoma, Angle-Closure genetics, Mutation
- Abstract
Primary angle-closure glaucoma (PACG) is a common form of glaucoma in the Far East. Its defining feature is iridocorneal angle closure. In addition to PACG, indications of angle closure are included in the diagnostic criteria of related conditions primary angle-closure suspect (PACS) and primary angle closure (PAC). To the best of our knowledge, a causative gene for iridocorneal angle closure in humans has not been identified. This study aimed to identify the genetic cause of iridocorneal angle closure in a pedigree with at least 10 individuals diagnosed with PACS, PAC or PACG. Results of linkage analysis, segregation analysis of 44 novel variations, whole exome sequencing of 10 individuals, screenings of controls and bioinformatics predictions identified a mutation in COL18A1 that encodes collagen type XVIII as the most likely cause of angle closure in the pedigree. The role of COL18A1 in the etiology of Knobloch syndrome (KS) that is consistently accompanied by optic anomalies, available functional data on the encoded protein and the recognized role of collagens and the extracellular matrix in glaucoma pathogenesis supported the proposed role of the COL18A1 mutation in the pedigree. Subsequent identification of other COL18A1 mutations in PACS affected individuals of two unrelated families further supported that COL18A1 may affect angle closure. These PACS individuals were parents and grandparents of KS-affected children. In conclusion, a gene that affects angle closure in humans, a critical feature of PACG, has been identified. The findings also reinforce the importance of collagens in eye features and functions.
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- 2018
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44. Effects of fibrin glue as a three-dimensional scaffold in cultivated adult human retinal pigment epithelial cells.
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Balagholi S, Rezaei Kanavi M, Alizadeh S, Dabbaghi R, Karami S, Kheiri B, and Daftarian N
- Subjects
- Actins genetics, Actins metabolism, Adult, Cell Line, Cell Proliferation, Cell Survival, Epithelial Cells metabolism, Humans, Keratin-8 genetics, Keratin-8 metabolism, Matrix Metalloproteinase 2 genetics, Matrix Metalloproteinase 2 metabolism, PAX6 Transcription Factor genetics, PAX6 Transcription Factor metabolism, Epithelial Cells cytology, Fibrin Tissue Adhesive chemistry, Retinal Pigment Epithelium cytology, Tissue Scaffolds chemistry
- Abstract
This study was conducted to examine morphological, genotypic, and phenotypic alterations occurring in cultured adult human retinal pigment epithelial cells when encapsulated with different concentrations of fibrin glue. Cultivated adult human retinal pigment epithelial cells were encapsulated with different concentrations of fibrin glue, namely FG1 (42 mg/dl), FG2 (84 mg/dl), FG3 (124 mg/dl), FG4 (210 mg/dl), followed by the evaluation of genetic and cytomorphological changes and protein expression. Cultured adult human retinal pigment epithelial cells showed dendritiform morphology during the early days of encapsulation with fibrin glue. Moreover, an increasing inhibitory effect on cell growth was observed with increasing concentrations of fibrin glue. At the transcriptional level, the expression of MMP2, PAX6, and ITGB1 in FG1-encapsulated cells was significantly higher than that in other treated groups; however, the expression of ACTA2 was lower in all fibrin glue-encapsulated groups compared to that in the controls. Immunocytochemistry showed that FG2-encapsulated cells expressed cytokeratin 8/18, RPE65, and ZO-1 proteins, but not PAX6. In conclusion, fibrin glue at a concentration of 84 mg/dl allows proper encapsulation of adult human retinal pigment epithelial cells, while preserving the morphometric, genotypic, and phenotypic features of the cells. This three-dimensional biopolymer can be considered a reliable vehicle for retinal pigment epithelium cell transplantation in cell-based therapies.
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- 2018
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45. Human organotypic retinal flat-mount culture (HORFC) as a model for retinitis pigmentosa11.
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Azizzadeh Pormehr L, Daftarian N, Ahmadian S, Rezaei Kanavi M, Ahmadieh H, and Shafiezadeh M
- Subjects
- Adult, Down-Regulation, Eye Proteins biosynthesis, Eye Proteins genetics, Female, Gene Knockdown Techniques, Humans, Male, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Small Interfering biosynthesis, RNA, Small Interfering genetics, Tissue Culture Techniques, Transfection, Models, Biological, Retina metabolism, Retina pathology, Retinitis Pigmentosa genetics, Retinitis Pigmentosa metabolism, Retinitis Pigmentosa pathology
- Abstract
The splicing factor PRPF31 is the most commonly mutated general splicing factor in the retinitis pigmentosa. We used a rapid, convenient and cost effective transfection method with an efficient PRPF31 knockdown in HORFC in order to study the effect of PRPF31 downregulation on retinal gene expressions in an ex vivo model. Modified calcium phosphate method was used to transfect HORFC by PRPF31 siRNA. Different times and doses of siRNA for transfection were assayed and optimum condition was obtained. PRPF31 mRNA and protein downregulation were assessed by qRTPCR and Western blot. The tissue viability of HORFC was measured using the MTT. ImageJ analysis on stained retinal sections by immunohistochemistry was used for thickness measurement of outer nuclear photoreceptor layer. The PRPF31 gene downregulation effects on retinal specific gene expression were analyzed by qRTPCR. A total of 50 nM of PRPF31 siRNA transfection after 63 h in HORFC, showed the optimum reduction in the level of PRPF31 mRNA and protein as shown by qRTPCR and Western blot (over 90% and 50% respectively). The PRPF31 mRNA silencing with calcium phosphate had no effect on cell viability in the period of the experiment. Thickness measurement of outer nuclear photoreceptor layer with IHC showed the significant reduction after 63 h of study (P value = 0.02). siRNA induced PRPF31 knockdown, led to reduction of retinal specific mRNA gene expression involved in phototransduction (RHO, GNAT1, RP1), photoreceptor structure (ROM1, FSCN2, CA4, SEMA4) and transcription factor (CRX) (fold change >5), after 63 h., (© 2018 Wiley Periodicals, Inc.)
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- 2018
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46. Intravitreal Injection of Anti-vascular Endothelial Growth Factor Agents for Ocular Vascular Diseases: Clinical Practice Guideline.
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Nikkhah H, Karimi S, Ahmadieh H, Azarmina M, Abrishami M, Ahoor H, Alizadeh Y, Behboudi H, Daftarian N, Dehghan MH, Entezari M, Farrahi F, Ghanbari H, Falavarjani KG, Javadi MA, Karkhaneh R, Moradian S, Manaviat MR, Mehryar M, Nourinia R, Parvaresh MM, Ramezani A, Haghi AR, Riazi-Esfahani M, Soheilian M, Shahsavari M, Shahriari HA, Rajavi Z, Safi S, Shirvani A, Rahmani S, Sabbaghi H, Pakbin M, Kheiri B, and Ziaei H
- Abstract
Purpose: To provide the clinical recommendations for the administration of intravitreal anti-vascular endothelial growth factor (VEGF) drugs especially bavacizumab for ocular vascular diseases including diabetic macular edema, neovascular age-related macular degeneration, myopic choroidal neovascularization, retinal vein occlusion and central serous chorioretinopathy., Methods: Twenty clinical questions were developed by the guideline technical committee. Relevant websites and databases were searched to find out the pertinent clinical practice guidelines to answer the questions. The technical committee provided possible answers (scenarios) according to the available evidences for each question. All scenarios along with their levels of evidence and the supported articles were sent to the experts for external review. If the experts did not agree on any of the scenarios for one particular clinical question, the technical committee reviewed all scenarios and their pertinent evidences and made the necessary decision. After that, the experts were asked to score them again. All confirmed scenarios were gathered as the final recommendations., Results: All the experts agreed on at least one of the scenarios. The technical committee extracted the agreed scenario for each clinical question as the final recommendation. Finally, 56 recommendations were developed for the procedure of intravitreal anti-VEGF injection and their applications in the management of ocular vascular diseases., Conclusion: The implementation of this guideline can standardize the management of the common ocular vascular diseases by intravitreal injection of anti-VEGF agents. It can lead to better policy-making and evidence-based clinical decision by ophthalmologists and optimal evidence based eye care for patients., Competing Interests: There are no conflicts of interest.
- Published
- 2018
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47. Survival and Migration of Adipose-Derived Stem Cells Transplanted in the Injured Retina.
- Author
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Aboutaleb Kadkhodaeian H, Tiraihi T, Ahmadieh H, Ziaei Ardakani H, Daftarian N, and Taheri T
- Subjects
- Adipose Tissue cytology, Animals, Cell Differentiation, Cell Survival, Cells, Cultured, Disease Models, Animal, Iodates, Male, Phenotype, Rats, Sprague-Dawley, Retinal Diseases chemically induced, Retinal Diseases pathology, Adipose Tissue transplantation, Cell Movement, Retinal Diseases surgery, Retinal Pigment Epithelium pathology, Stem Cell Transplantation methods
- Abstract
Objectives: Transplantation of stem cells is one of the approaches to treat retinal diseases. Our objective was to determine whether adipose-derived stem cell transplant can survive and migrate in the injured retina using a sodium iodate model for the pigmented retinal epithelium injury., Materials and Methods: The adipose-derived stem cells were isolated from male albino Sprague-Dawley rats and labeled with DiI so as to track the transplants in the subretinal space. Retinal pigmented epithelium damage was induced by retro-orbital sinus sodium iodate injection (40 mg/kg) into albino Sprague-Dawley rats. Four weeks after transplantation, the eyeballs were fixed in 4% paraformaldehyde and cut with cryostat. The eyeballs were serially sectioned along the vertical meridian. Cryosections were from the full length of the retina and passing through the optic nerve head. The survival and migration of transplanted cells were assessed., Results: Sodium iodate selectively destroyed the retinal pigmented epithelium layer. The transplanted cells incorporated into the retinal pigmented epithelium layer, perhaps differentiating into a retinal pigmented epithelium phenotype. The transplanted cells were located in the subretinal space; after 4 weeks, some were observed in the retinal pigmented epithelium layer., Conclusions: We found that adipose-derived stem cells survived for 4 weeks after transplantation and migrated into the retinal pigmented epithelium layer.
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- 2018
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48. A novel c.240_241insGG mutation in NDP gene in a family with Norrie disease.
- Author
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Andarva M, Jamshidi J, Ghaedi H, Daftarian N, Emamalizadeh B, Alehabib E, Taghavi S, Pouriran R, and Darvish H
- Subjects
- Adult, Blindness diagnosis, Blindness genetics, Child, DNA Mutational Analysis, Exons genetics, Genetic Diseases, X-Linked diagnosis, Humans, Iran, Male, Middle Aged, Nervous System Diseases diagnosis, Pedigree, Phenotype, Polymerase Chain Reaction, Retinal Degeneration, Spasms, Infantile diagnosis, Blindness congenital, Eye Proteins genetics, Frameshift Mutation genetics, Genetic Diseases, X-Linked genetics, Nerve Tissue Proteins genetics, Nervous System Diseases genetics, Spasms, Infantile genetics
- Abstract
Background: Norrie disease (ND) is a rare, X-linked recessive disorder with the main characteristic of early childhood blindness. The aim of the present study was to identify the genetic cause of the disease and the phenotypic characteristics of the patients in an Iranian family with four affected males with ND., Methods: Norrie disease pseudoglioma (NDP) gene was sequenced and clinical examination was performed on patients., Results: A GG dinucleotide insertion in exon 3 (c.240_241insGG) of NDP was detected in all patients. The mutation caused a frameshift and an early stop codon (p.Phe81Glyfs*23)., Conclusions: A novel mutation was found in the NDP gene in the affected males of the family. As the mutation was absent in the normal male members of the family, it should be the genetic cause of the disease., (© 2017 Optometry Australia.)
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- 2018
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49. Novel Mutations in TACSTD2 Gene in Families with Gelatinous Drop-like Corneal Dystrophy (GDLD).
- Author
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Alehabib E, Jamshidi J, Ghaedi H, Emamalizadeh B, Andarva M, Daftarian N, Rezaei Kanavi M, Mohammadi Torbati P, Espandar G, Alinaghi S, Johari AH, Saghally M, Mohajerani F, and Darvish H
- Abstract
In the current study, we conducted a mutation screening of tumor-associated calcium signal transducer 2 ( TACSTD2 ) gene in six consanguineous Iranian families with gelatinous drop-like corneal dystrophy (GDLD), in order to find the causative mutations. Detailed eye examination was performed by ophthalmologist to confirm GDLD in patients. To detect the possible mutations, direct Sanger sequencing was performed for the only exon of TACSTD2 gene, and its boundary regions in all patients. In the patients with GDLD, the corneal surface showed lesions with different shapes from mild to severe forms depending on the progress of the disease. The patients showed grayish corneal deposits as a typical mulberry form, corneal dystrophy along with corneal lipid deposition, and vascularization. Targeted Sanger sequencing in TACSTD2 gene revealed the causative mutations in this gene in all studied families. Our study expanded the mutational spectrum of TACSTD2 which along with the related symptoms could help with the diagnosis, and management of the disease., Competing Interests: The authors disclose that there is no conflict of interest.
- Published
- 2017
- Full Text
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50. Ocular Safety of Intravitreal Connective Tissue Growth Factor Neutralizing Antibody.
- Author
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Motevasseli T, Daftarian N, Kanavi MR, Ahmadieh H, Bagheri A, Hosseini SB, Ansari S, and Soheili ZS
- Subjects
- Animals, Connective Tissue Growth Factor immunology, Disease Models, Animal, Electroretinography, In Situ Nick-End Labeling, Intravitreal Injections, Male, Rats, Retina drug effects, Retinal Diseases diagnosis, Retinal Diseases physiopathology, Vitreous Body drug effects, Antibodies, Neutralizing administration & dosage, Connective Tissue Growth Factor administration & dosage, Retina pathology, Retinal Diseases drug therapy, Vitreous Body pathology
- Abstract
Purpose: To detect the safety of intravitreal injection of anti-connective tissue growth factor (CTGF) (IVAC) in rat eyes in order to apply this neutralizing antibody for experimental animal studies., Methods: Forty-five Lister Hooded male pigmented rats were divided into five groups that received IVAC (2 μl) corresponding to the doses of 10 (B), 20 (C), 50 (D), and 100 μg/ml (E), equal to 1.25, 2.5, 6.25, and 12.5 µg/ml of antibody concentration in rat vitreous, respectively. The sham group (A) received 2 μl of normal saline. Full field electroretinography (ERG) was performed at baseline and on days 7 and 28 after IVAC. The animals were euthanized and the corresponding eyes were subjected to routine histopathology, immunohistochemistry for glial fibrillary acidic protein (GFAP), and terminal transferase dUTP nick end-labeling (TUNEL) assay., Results: Scotopic rod b-wave amplitude and maximal combined b-wave amplitude were 111.89 ± 71.2 and 178.57 ± 55.58 μV, respectively, at baseline which significantly reduced to 79.31 ± 52.59 and 128.73 ± 41.61 μV, respectively, after 28 days in group E (p < 0.05). There was no significant reduction of amplitudes in other groups with lower doses of anti-CTGF antibody. Retinal ganglion cells were significantly decreased in group E as compared to other groups. GFAP immune reactivity was not significant in any of the groups. TUNEL test showed inner retinal neural cell apoptosis only in group E., Conclusions: ERG, histopathologic, and apoptotic assays revealed no toxic effects of 10-50 μg/ml of IVAC in rat eyes. Using 100 μg/ml IVAC led to a significant toxic effect in terms of functional, histopathologic, and TUNEL findings.
- Published
- 2017
- Full Text
- View/download PDF
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