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38 results on '"Sinha, Prashant R."'

10. Tissue-targeted and localized AAV5-DCNand AAV5-PEDFcombination gene therapy abrogates corneal fibrosis and concurrent neovascularization in rabbit eyes in vivo

Author

Mohan, Rajiv R., Gupta, Suneel, Kumar, Rajnish, Sinha, Nishant R., Landreneau, James, Sinha, Prashant R., Tandon, Ashish, Chaurasia, Shyam S., and Hesemann, Nathan P.

Abstract

Corneal fibrosis and neovascularization (CNV) after ocular trauma impairs vision. This study tested therapeutic potential of tissue-targeted adeno-associated virus5 (AAV5) mediated decorin (DCN) and pigment epithelium-derived factor (PEDF) combination genes in vivo.

Published
2024
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15. A Novel Topical Ophthalmic Formulation to Mitigate Acute Mustard Gas Keratopathy In Vivo: A Pilot Study

Author

Tripathi, Ratnakar, primary, Balne, Praveen K., additional, Sinha, Nishant R., additional, Martin, Lynn M., additional, Kamil, Sabeeh, additional, Landreneau, James R., additional, Gupta, Suneel, additional, Rodier, Jason T., additional, Sinha, Prashant R., additional, Hesemann, Nathan P., additional, Hofmann, Alexandria C., additional, Fink, Michael K., additional, Chaurasia, Shyam S., additional, and Mohan, Rajiv R., additional

Published
2020
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17. Hydrogen Sulfide Gas Toxicity to the Cornea

Author

Balne, Praveen K., primary, Hofmann, Alexandria C., additional, Shina, Nishant R., additional, Tripathi, Ratnakar, additional, Martin, Lynn, additional, Anand, Kavin, additional, Fraunfelder, Fredrick W., additional, Kamil, Sabeeh, additional, Sinha, Prashant R., additional, Gupta, Suneel, additional, Hesemann, Nathan P., additional, and Mohan, Rajiv R., additional

Published
2020
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18. Acrolein Disrupts Corneal Natural Defense Mechanism

Author

Gupta, Suneel, primary, Sinha, Prashant R, additional, Heil, Sally, additional, Balne, Praveen, additional, Hesemann, Nathan P, additional, Rodier, Jason T, additional, Tripathi, Ratnakar, additional, Fraunfelder, Frederick T, additional, Giuliano, Elizabeth A, additional, Chaurasia, Shyam S, additional, and Mohan, Rajiv R, additional

Published
2020
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19. Chlorine Gas Toxicity to the Cornea

Author

Tripathi, Ratnakar, primary, Martin, Lynn, additional, Kamil, Sabeeh, additional, Sinha, Nishant R., additional, Hofmann, Alexandria, additional, Green, Sydney, additional, Balne, Praveen, additional, Sinha, Prashant R., additional, Hesemann, Nathan P., additional, Veress, Livia A., additional, Fraunfelder, Fredrick W., additional, and Mohan, Rajiv R., additional

Published
2020
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20. Turbo Eye Drops Restore Sulfur Mustard-Induced Corneal Damage

Author

Martin, Lynn M., primary, Tripathi, Ratnakar, additional, Balne, Praveen, additional, Landreneau, James, additional, Kamil, Sabeeh, additional, Gupta, Suneel, additional, Hesemann, Nathan P., additional, Sinha, Prashant R., additional, Rodier, Jason T., additional, Green, Sydney L., additional, Sinha, Nishant R., additional, Hofmann, Alexandria, additional, Fraunfelder, Frederick W., additional, Chaurasia, Shyam S., additional, and Mohan, Rajiv R., additional

Published
2020
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21. Rescue of Limbal Stem Cell Deficiency in the Cornea by a Proprietary Eye Drop in Rabbits Exposed to the Sulphur Mustard Gas

Author

Kamil, Sabeeh, primary, Tripathi, Ratnakar, additional, Landreneau, James, additional, Balne, Praveen, additional, Martin, Lynn, additional, Hesemann, Nathan P., additional, Sinha, Prashant R., additional, Gupta, Suneel, additional, Rodier, Jason T., additional, Green, Sydney L., additional, Sinha, Nishant R., additional, Hofmann, Alexandria, additional, Fraunfelder, Frederick, additional, and Mohan, Rajiv R., additional

Published
2020
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22. Corneal fibrosis abrogation by a localized AAV-mediated inhibitor of differentiation 3(Id3) gene therapy in rabbit eyes in vivo

Author

Gupta, Suneel, Fink, Michael K., Kempuraj, Duraisamy, Sinha, Nishant R., Martin, Lynn M., Keele, Landon M., Sinha, Prashant R., Giuliano, Elizabeth A., Hesemann, Nathan P., Raikwar, Sudhanshu P., Chaurasia, Shyam S., and Mohan, Rajiv R.

Abstract

Previously we found that inhibitor of differentiation 3(Id3) gene, a transcriptional repressor, efficiently inhibits corneal keratocyte differentiation to myofibroblasts in vitro. This study evaluated the potential of adeno-associated virus 5 (AAV5)-mediated Id3gene therapy to treat corneal scarring using an established rabbit in vivodisease model. Corneal scarring/fibrosis in rabbit eyes was induced by alkali trauma, and 24 h thereafter corneas were administered with either balanced salt solution AAV5-naked vector, or AAV5-Id3 vector (n = 6/group) via an optimized reported method. Therapeutic effects of AAV5-Id3 gene therapy on corneal pathology and ocular health were evaluated with clinical, histological, and molecular techniques. Localized AAV5-Id3 gene therapy significantly inhibited corneal fibrosis/haze clinically from 2.7 to 0.7 on the Fantes scale in live animals (AAV5-naked versus AAV5-Id3; p < 0.001). Furthermore, AAV5-Id3 treatment significantly reduced profibrotic gene mRNA levels: α-smooth muscle actin (α-SMA) (2.8-fold; p < 0.001), fibronectin (3.2-fold; p < 0.001), collagen I (0.8-fold; p < 0.001), and collagen III (1.4-fold; p < 0.001), as well as protein levels of α-SMA (23.8%; p < 0.001) and collagens (1.8-fold; p < 0.001). The anti-fibrotic activity of AAV5-Id3 is attributed to reduced myofibroblast formation by disrupting the binding of E-box proteins to the promoter of α-SMA, a transforming growth factor-β signaling downstream target gene. In conclusion, these results indicate that localized AAV5-Id3 delivery in stroma caused no clinically relevant ocular symptoms or corneal cellular toxicity in the rabbit eyes.

Published
2022
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24. A rabbit model for evaluating ocular damage from acrolein toxicity in vivo.

Author

Gupta, Suneel, Fink, Michael K., Martin, Lynn M., Sinha, Prashant R., Rodier, Jason T., Sinha, Nishant R., Hesemann, Nathan P., Chaurasia, Shyam S., and Mohan, Rajiv R.

Subjects
BENZALKONIUM chloride, WORLD War I, CORNEA, RABBITS, ACROLEIN, OCULAR injuries
Abstract

Acrolein is a highly reactive and volatile unsaturated aldehyde commonly used for producing scores of commercial products. It has been recognized as a chemical weapon since its use during World War I, and more recently, in Syria. Acrolein exposure causes severe eye, skin, and lung damage in addition to many casualties. In the eye, it causes severe pain, eyelid swelling, corneal burns, and vision impairment. Very little information is available about how acrolein damages the cornea and causes vision loss. At present, the lack of clinically relevant animal models limits evaluation of acrolein toxicity and mechanisms specific to the eye. We aim to standardize the mode of delivery and exposure duration of acrolein, damaging the rabbit eye in vivo as an ocular injury model for studying the toxicity of acrolein and developing medical countermeasures. Rabbit eyes were exposed to two modes of delivery (topical and vapor) for different durations (1–5 minutes). Clinical ophthalmic examinations with a slit lamp, stereomicroscope, fluorescein dye, pachymeter, tonometer, and tearing examinations in live rabbits were performed at various times up to 4 weeks. Corneas were histologically diagnosed for transparency, fibrosis, collagens, and neovascularization. Our study successfully established an in vivo rabbit model for evaluating acrolein toxicity to the eye, accounting for different modes and durations of exposure. [ABSTRACT FROM AUTHOR]

Published
2020
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31. Anti‐fibrotic effects of lisinopril (ACE inhibitor) and fasudil (ROCK inhibitor) in combination for canine corneal fibrosis in vitro.

Author

Routh, Brayden L., Tripathi, Ratnakar, Giuliano, Elizabeth, Lujin, Payton, Sinha, Prashant R., and Mohan, Rajiv R.

Subjects
*TRANSFORMING growth factors, *LISINOPRIL, *ACE inhibitors, *ANGIOTENSIN I, *CYTOTOXINS, *TENASCIN
Abstract

Background Methods Results Conclusion Corneal fibrosis is a leading cause of blindness in mammalian species and may result in compromised performance in sports and daily functions. This study evaluated the safety and anti‐fibrotic effects of the FDA‐approved drugs, angiotensin‐converting enzyme inhibitor (ACE‐I) lisinopril and rho‐kinase inhibitor (ROCK‐I) fasudil, alone and in combination, on the canine cornea using an established in vitro model.To test the safety and efficacy of lisinopril and fasudil, primary canine corneal fibroblasts (CCFs) generated from donor corneas of healthy dogs (n = 20) were used. A series of dose‐dependent and time‐dependent assays with lisinopril (1–50 μM) and fasudil (1–10 nM) were performed. qRT‐PCR, immunofluorescence (IF) staining, cell viability assay, cell proliferation assay, LIVE/DEAD viability/cytotoxicity assay, TUNEL assay, and total cell count were performed.A 25‐μM lisinopril and 3‐nM fasudil dose were safe, nontoxic, and optimal for therapeutic evaluations in vitro. Treatments of lisinopril or fasudil, alone or in‐combination, to CCFs grown in the presence of TGF‐β1 (5 ng/mL) showed inhibition of myofibroblast formation based on phase‐contrast microscopy. The qRT‐PCR and IF studies showed a significant decrease in expression of profibrotic markers, including α‐smooth muscle actin (α‐SMA; p < .0001), fibronectin (FN; p = .0002), tenascin C (TNC; p < .0001), Collagen I (Col‐I; p < .0001), Collagen IIIA1 (Co‐IIIA1; p < .0001), and Collagen IV (Co‐lV; p < .0001).An ophthalmic formulation consisting of lisinopril and fasudil may offer a safe and effective method to treat canine corneal fibrosis. Additional studies evaluating safety and efficacy of this formulation in vivo are warranted. [ABSTRACT FROM AUTHOR]

Published
2024
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37. Role of inhibitor of differentiation 3 gene in cellular differentiation of human corneal stromal fibroblasts

Author

Suneel Gupta, Martin, Lynn M., Sinha, Nishant R., Smith, Kaitlin E., Sinha, Prashant R., Dailey, Emilee M., Hesemann, Nathan P., and Mohan, Rajiv R.

Subjects
Research Article
Abstract

Purpose Inhibitor of differentiation (Id) proteins are helix–loop–helix (HLH) transcriptional repressors that modulate a range of developmental and cellular processes, including cell differentiation and cell cycle mobilization. The inhibitor of differentiation 3 (Id3) gene, a member of the Id gene family, governs the expression and progression of transforming growth factor beta (TGFβ)-mediated cell differentiation. In the face of mechanical, chemical, or surgical corneal insults, corneal keratocytes differentiate into myofibroblasts for wound repair. Excessive development or persistence or both of myofibroblasts after wound repair results in corneal haze that compromises corneal clarity and visual function. The objective of this study was to investigate whether Id3 overexpression in human corneal stromal fibroblasts governs TGFβ-driven cellular differentiation and inhibits keratocyte to myofibroblast transformation. Methods Primary human corneal stromal fibroblast (h-CSF) cultures were generated from donor human corneas. Human corneal myofibroblasts (h-CMFs) were produced by growing h-CSF in the presence of TGFβ1 under serum-free conditions. The Id3 gene was cloned into a mammalian expression vector (pcDNA3 mCherry LIC cloning vector), and the nucleotide sequence of the vector constructs was confirmed with sequencing as well as through restriction enzyme analysis. The Id3 mammalian overexpression vector was introduced into h-CSFs using a lipofectamine transfection kit. The expression of Id3 in selected clones was characterized with quantitative real-time PCR (qRT–PCR), immunocytochemistry, and western blotting. Phase contrast microscopy and trypan blue exclusion assays were used to evaluate the effects of the transfer of the Id3 gene on the hCSF phenotype and viability, respectively. To analyze the inhibitory effects of the Id3 gene transfer on TGFβ-induced formation of h-CMFs, expression of the mRNA and protein of the myofibroblast marker alpha smooth muscle actin (α-SMA) was examined with qRT–PCR, western blotting, and immunocytochemistry. Student t test, analysis of variance (ANOVA), and Bonferroni adjustment for repeated measures were used for statistical analysis. Results The results indicate that Id3 overexpression does not alter the cellular phenotype or viability of h-CSFs. Overexpression of the Id3 gene in h-CSF cells grown in the presence of TGFβ1 under serum-free conditions showed a statistically significant decrease (76.3±4.3%) in α-SMA expression (p

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