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4. Targeted Gene Candidates for Treatment and Early Diagnosis of Age-Related Macular Degeneration

Author

Cinici, Emine, Caglar, Ozge, Arslan, Mehmet Enes, Dilekmen, Nilay, Utlu, Bahadır, Mardinoglu, Adil, and Turkez, Hasan

Subjects
Article Subject, Middle Aged, eye diseases, Macular Degeneration, Early Diagnosis, Molecular Diagnostic Techniques, Humans, Medicine, Female, Protein Interaction Maps, Transcriptome, Research Article, Aged
Abstract

Age-related macular degeneration (AMD) is an eye disease that impairs the sharp and central vision need for daily activities. Recent advances in molecular biology research not only lead to a better understanding of the genetics and pathophysiology of AMD but also to the development of applications based on targeted gene expressions to treat the disease. Clarification of molecular pathways that causing to development and progression in dry and wet types of AMD needs comprehensive and comparative investigations in particular precious biopsies involving peripheral blood samples from the patients. Therefore, in this investigation, dry and wet types of AMD patients and healthy individuals were aimed at investigating in regard to targeted gene candidates by using gene expression analysis for the first time. 13 most potent candidate genes involved in neurodegeneration were selected via in silico approach and investigated through gene expression analysis to suggest new targets for disease therapy. For the analyses, 30 individuals (10 dry and 10 wet types AMD patients and 10 healthy people) were involved in the study. SYBR-Green based Real-Time PCR analysis was performed on isolated peripheral blood mononuclear cells (PBMCs) to analyze differentially expressed genes related to these cases. According to the investigations, only the CRP gene was found to be upregulated for both dry and wet disease types. When the downregulated genes were analyzed, it was found that 11 genes were commonly decreased for both dry and wet types in the aspect of expression pattern. From these genes, CFH, CX3CR1, FLT1, and TIMP3 were found to have the most downregulated gene expression properties for both diseases. From these results, it might be concluded that these common upregulated and downregulated genes could be used as targets for early diagnosis and treatment for AMD.

Published
2021

11. Carvacrol Protects Against Paclitaxel-Induced Retinal and Optic Nerve Cytotoxicity: A Histopathological Study.

Author

Cinici, Emine, Dilekmen, Nilay, Kutlu, Zerrin, Dincer, Busra, Cinici, Ozkan, Balta, Hilal, and Calik, Ilknur

Subjects
CARVACROL, OPTIC nerve diseases, CELL-mediated cytotoxicity, OXIDATIVE stress, ANTIOXIDANTS
Abstract

Objectives: Carvacrol (CV) is a phenolic monoterpenoid found in the essential oil of a number of aromatic plants and herbs. The present study was an investigation of the potential protective effect of CV against paclitaxel (PTX)-induced retinal and optic nerve cytotoxicity in rats. Methods: A total of 18 adult male Wistar albino rats (250-400g) were randomized into 3 equal groups comprising 6 animals each. Group 1 (control group) received intraperitoneal (IP) saline solution (0.5 mL/200 g) weekly for 4 weeks. Group 2 received an IP dose of PTX (5 mg/kg), and Group 3 received CV (25 mg/kg) 30 minutes after an IP dose of PTX (5 mg/ kg) weekly for 4 weeks. At the conclusion of the experimental period, the retinal and optic nerve tissues of the subjects were evaluated histopathologically. Results: All of the retinal specimens in Group 1 (control) were histopathologically normal. In Group 2 (PTX), all of the eyes (6/6) revealed increased retinal vascularity and rosette-like structures in the outer nuclear layer, and in Group 3 (PTX-CV), all of the eyes (6/6) demonstrated normal retinal vascularity and the absence of rosette-like structures. All of the optic nerve specimens in Group 1 (control) were histopathologically normal. In Group 2 (PTX), all of the eyes (6/6) demonstrated severe vacuolization and a decreased number of astrocytes and oligodendrocytes in the optic nerve specimens, while 3 eyes (3/6) showed marked single cell necrosis. None of the eyes in Group 3 (PTX-CV) demonstrated either vacuolization or a reduction in the number of astrocytes and oligodendrocytes. No remarkable single cell necrosis was observed in the optic nerve specimens of Group 3 (PTX-CV). Conclusion: The histopathological findings indicated that CV played a protective role against PTX-induced cytotoxicity. CV might be a promising resource to counteract oxidative stress-based cytotoxicity in the field of retinal and optic nerve disorders. [ABSTRACT FROM AUTHOR]

Published
2020
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17. Başarısız trabekülektomi sonrası 2. cerrahi olarak retrabekülektomi ile çepeçevre sütür trabekülotomi'nin karşılaştırılması

Author

Dilekmen, Nilay, Aktaş, Zeynep, and Göz Hastalıkları Anabilim Dalı

Subjects
Surgical treatment, Göz Hastalıkları, Eye Diseases, Sutures, Intraocular pressure, Trabeculectomy, Glaucoma, Surgery-eye, Eye diseases
Abstract

İlk glokom ameliyatı olarak trabekülektomi(TE) yapılmış ve sonrası geçdönem bleb yetmezliği gelişen erişkin açık açılı glokom (AAG) olgularındageleneksel yöntemlerden Mitomisin C ile retrabekülektomi(MMC re-TE) vegüncel bir SK cerrahisi olan çepeçevre (360º) sütür trabekülotomi (STO)ameliyatlarının klinik sonuçlarını karşılaştırmak.MATERYAL VE METOD:Kliniğimizde trabekülektomi(TE) sonrası geç bleb yetmezliği tanısıkonularak Mitomisin C'li retrabekülektomi (MMC re-TE) yapılan 22 hastanın 22gözü ve çepeçevre STO uygulanan 21 hastanın 22 gözü dahil edildi. Olgulara aityaş, cinsiyet, aile öyküsü, glokom tipi, lens durumu, C/D oranı, takip süresi veinterval süreleri kaydedildi. Preoperatif ve postoperatif 1., 3., 6. ve 12. ay vizitlerindeki Goldmann aplanasyon tonometresiyle GİB ve antiglokomatözmedikasyon sayıları değerlendirildi. Her 2 gruba ait mutlak ve kısmi cerrahi başarıoranları hesaplandı. Perioperatif ve postoperatif komplikasyonlar kaydedildi.BULGULAR:MMC re-TE grubuna 22 hastanın 22 gözü dahil edilmiştir. Ortalama takipsüresi 15.5 ± 3.5 (12-24) ay;ortalama interval 5 ± 2.6 (2-10) yıl idi. Glokomtipi olarak olgularımızın 16'sını (%73) PAAG, 6'sını (% 27) psödoeksfolyatifglokom oluşturmaktaydı. Cerrahi öncesi 12 göz psödofakik, 10 göz fakik oluphiçbir göze fako ile kombine cerrahi uygulanmamıştı. Çepeçevre STO grubuna 21hastanın 22 gözü dahil edilmiştir. Ortalama takip süresi 13.6 ± 2.2 (12-20) ay; ilkve ortalama interval 5.7 ± 2.5 (2-10) yıl idi. Gözlerin 8'ini (%36) primer açık açılıglokom (PAAG) ; 10'unu (% 45) psödoeksfolyatif glokom, 2'sini üveitik glokom(%9), 1'ini (%5) steroide bağlı glokom, 1'ini (%5) pigmenter glokomoluşturmaktaydı. Cerrahi öncesi 12 göz psödofakik, 10 göz fakik olup; 11 göze abexterno sütür trabekülotomi, 5 göze fako-ab externo sütür trabekülotomi, 4 göze abinterno sütür trabekülotomi ve 2 göze fako-ab interno sütür trabekülotomi uygulanmıştı.MMC re-TE grubunda preoperatif ortalama GİB 25.8±3.1 (19-30) mmHg;preoperatif ortalama ilaç sayısı 3.0±0.2 (2-4) olarak belirlendi. Postoperatif 1., 3 . ,6.ve 12. ayvizitlerinde ortalama GİB değerleri sırası ile 15.3±1.9 (9-18), 15.6±1.5(13-20), 16.6±1.2 (14-19 ) ve 16.9±1.4 (14-20) idi. Aynı vizitlerdeki ortalama antiglokom medikasyon sayıları sırası ile 0.8±0.7(0-2), 0.8±0.7 (0-2), 0.8±0.5 (0-2)ve 0.9±0.9 (0-2) idi. Postoperatif bütün vizitlerde hem ortalama GİB hem deortalama antiglokom ilaç sayısı preoperatif (baseline) değerlere göre anlamlı olarakdüşüktü (p< .001). 12. ay vizitinde preoperatif değere göre ortalama GİB düşüşyüzdesi 34.9±10.1 (10-50) idi. Mutlak başarı %36, kısmi başarı %86, cerrahibaşarısızlık %14'tü. 3 gözde hipotoni, 1 gözde hipotoni makülopatisi, 2 gözdehifema, 1 gözde üveitik reaksiyon, 1 gözde koroid dekolmanı, 1 gözde bleb ilişkiliendoftalmi gelişmişti.Çepeçevre STO ve MMC re-TE gruplarını karşılaştırırsak her 2 grupta dapostoperatif tüm vizitlerde GİB ve antiglokom medikasyon sayısının preoperatifdeğerlere göre anlamlı düşük olduğunu gördük. 1. ay vizitinde 2 grup arasında GİBve medikasyon sayıları yönüyle anlamlı fark bulunmazken 1. Aydan sonraki tümvizitlerde (3., 6., ve 12. aylar) STO grubunda gerek ort. GİB gerekse ortalamamedikasyon sayısı anlamlı olarak düşük bulunmuştur. MMC re-TE grubundabaseline değere göre % 34.9'lık GİB düşüşü gerçekleşirken; çepeçevre STOgrubunda bu oran 38.2 idi. Mutlak başarı oranı(A) çepeçevre STO grubunda %82iken MMC re-TE grubunda %36 idi.SONUÇÇepeçevre sütür trabekülotomi bleb yetmezliği gelişmiş trabekülektomiligözlerde gerek klinik etkinlik gerekse düşük komplikasyon oranı ile MMC ileretrabekülektomiye iyi bir alternatif olabilir.Anahtar kelimeler: MMC ile retrabekülektomi, çepeçevre sütür trabekülotomi,antiglokom medikasyon sayısı, göz içi basıncı, cerrahi başarı To compare and evaluate the clinical outcomes of MMC augmentedretrabeculectomy and 360º suture trabeculotomy in eyes with late bleb failure.MATERIAL AND METHOD22 eyes of 22 patients who underwent MMC re-TE surgery and 22 eyes of 21patients who underwent 360 º STO were included. Demographic properties (age,sex, family history, glaucoma type, lens status, cup/disc ratio, follow up time andinterval time) were recorded. Intraocular pressure and number of glaucomamedications were evaluated both preoperatively and at control visits (1,3,6,12months postoperatively). Also all surgical complications were recorded.RESULTSFor MMC re-TE group mean follow up time was 15.5 ± 3.5 (12-24) months;while mean interval was 5 ± 2.6 (2-10) years. 16 (%73) of eyes were POAG and 6(% 27) were exfoliative Glaucoma. For 360º STO group, mean follow up time was13.6 ± 2.2 (12-20) months; while mean interval was 5.7 ± 2.5 (2-10) years. 8 (%36)of eyes were POAG, 10 (% 45) were exfoliative glaucoma, 2(%9) were uveiticglaucoma, 1(%5) was steroid induced glaucoma , 1(%5) was pigmentary glaucoma.118For MMC re-TE group mean preoperative IOP was 25.8±3.1 (19-30) mmHgwhile mean number of glaucoma medications was 3.0±0.2 (2-4). Mean IOPpostoperatively at 1, 3, 6 and 12 months were 15.3±1.9 (9-18), 15.6±1.5 (13-20),16.6±1.2 (14-19 ) and 16.9±1.4 (14-20) mm Hg. Mean number of glaucomamedications at same visits were 0.8±0.7(0-2), 0.8±0.7 (0-2), 0.8±0.5 (0-2) and0.9±0.9 (0-2) respectively. Decrease in IOP from baseline was %34.9±10.1 (10-50).Succes rates were: %36 complete (IOP ˂18 mm Hg without medication) , %86relative (IOP ˂18 mm Hg with or without medication) and %14 no succes (IOP ˃18mmHg). Recorded complications were: hypotony(3 eyes), hypotony maculopathy(1 eye), hyphema(2 eyes), anterior uveitis(1 eye), choroid detachment(1 eye), blebrelated endophtalmitis (1eye). 2 eyes in this group needed 5-FU augmentedneedling for early bleb failure.For 360º STO group, mean preoperative IOP was 26.3±6.8 (19-38) mm Hgwhile mean number of glaucoma medications was3.4±1.0 (2-4). Mean IOPpostoperatively at 1, 3, 6 and 12 months were 15.2±5.8 (5-30), 13.9±3.0 (8-20),14.4±2.5 ( 10-19 ) and 14.7±1.9 (11-18) mm Hg. Mean number of glaucomamedications at same visits were 0.4 ±0.7 (0-2), 0.2±0.5 (0-2), 0.3±0.5 (0-2) and0.3±0.6 (0-2) respectively. Decrease in IOP from baseline was %38.2 ±17.3 (10-63). Succes rates were: %82 complete and %100 relative. Recorded complicationswere: hypotony (1 eye), posterior synechia (1 eye), transient IOP rise (2 eyes),macrohyphema(2 eyes), microhyphema(15 eyes), persistant hemorrhagic membranbehind the intraocular lens (1eye).CONCLUSIONCompared with MMC augmented retrabeculectomy, 360º suturetrabeculotomy can provide better postoperative results with less complications inthe surgical management of late bleb failure.Key words: MMC augmented retrabeculectomy, 360º suture trabeculotomy,antiglaucoma medication number, intraocular pressure , surgical succes 121

Published
2015

20. The Effect of Topical and Subconjunctival Coenzyme Q10 on Wound Healing Modulation in an Experimental Trabeculectomy Model.

Author

Bektaş, Çağlar, Atalay, Hatice Tuba, Seymen, Cemile Merve, Dilekmen, Nilay, Aktaş, Zeynep, and Elmas, Çiğdem

Subjects
*UBIQUINONES, *TRABECULECTOMY, *WOUND healing, *LABORATORY rats, *MITOMYCIN C, *RATS
Abstract

Purpose: To investigate the wound healing effect of topical and subconjunctival Coenzyme Q10 (CoQ) in an experimental trabeculectomy model, and to compare the outcomes with mitomycin C and bevacizumab. Materials and Methods: Thirty eyes of 27 Wistar Albino rats were included. Group 1 was the control group and the other four groups were mitomycin C (group 2), topical CoQ (group 3), subconjunctival CoQ (group 4), and bevacizumab (group 5). Conjunctival and scleral incisions were made to mimic the trabeculectomy wound. After the rats were sacrificed, histological sections were examined for vasculogenesis, VEGF and TGF-β1 positivity. Results: The mean vascularization score was lowest in groups 3 and 4 (0.5±0.55). It was followed by group 2 (1.0± 0.89), group 5 (1.5±1.0), and control group (2.5±0.55). The eyes in group 2, 3 and 4 showed significantly less vascularization than the control group (p = 0.015, p <0.01, p <0.01). VEGF and TGF-β1 positivity scores were lowest in groups 3 and 4 (1.48±0.45). This was followed by group 2 (2.0±0.34), group 5 (3.5±0.3), and control group (3.94±0.5). TGF-β1 and VEGF positive cells were significantly lower in groups 2, 3 and 4 than group 1 (p <0.01). TGF-β1 and VEGF positivity in groups 3 and 4 were significantly lower than the group 2 (p = 0.04). Conclusion: The application of topical and subconjunctival CoQ resulted in inhibition of vasculogenesis and reduction of TGF-β1 and VEGFpositive cells in trabeculectomy wound healing model. Topical or subconjunctival application of CoQ in trabeculectomy surgery may provide positive effects on wound healing.. [ABSTRACT FROM AUTHOR]

Published
2021
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21. Descemet Membrane Endothelial Keratoplasty with Irregular-Edged Graft: A Salvage Method for Large Radial Graft Tears.

Author

Özmen MC, Dilekmen N, Yüksel E, Aydın B, and Akata F

Abstract

Large radial tears of donor Descemet membrane (DM) during the preparation of Descemet membrane endothelial keratoplasty (DMEK) grafts can make the trephination stage impossible because of small graft diameter. This results in irregular-edged grafts. In this study, we report two pseudophakic bullous keratopathy patients who underwent DMEK surgery with irregular-edged Descemet membrane (DM) grafts. Main outcome measures were preoperative and postoperative 1-, 3-, and 6-month best corrected visual acuity (BCVA), endothelial cell density (ECD) and central corneal thickness (CCT). Intraoperative and early postoperative complications were also evaluated. Both irregular-edged grafts were successfully implanted into the anterior chamber, unfolded, and attached to the posterior corneal stroma. Patients' BCVA at 6 months was 1.0 (Snellen equivalent: 20/20) and 0.6 (Snellen equivalent: 20/32) respectively. Decrease in ECD at the last visit was 27% and 25%. CCT decreased from 723 μm and 850 μm to 530 μm and 523 μm, respectively. No intraoperative complications occurred except for the large radial Descemet membrane graft tears that developed during donor DM stripping. None of the cases needed a rebubbling procedure postoperatively. We have demonstrated that irregular-edged DM grafts can be successfully implanted for DMEK surgery with good clinical outcomes., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Published
2018
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