Effect of the rho-kinase inhibitor Netarsudil on established corneal neovascularization in a PAX-6 knockout mouse model

Project: Research project

Project Details

Description

Corneal neovascularization (CNV) is a consequence of a variety of ocular pathologies including infectious, autoimmune, and post-transplantation etiologies. CNV can frequently lead to corneal opacification and loss of visual acuity. The GTPase RhoA and its downstream effectors ROCK1 and ROCK2 play an important role in VEGF mediated proangiogenic endothelial cell polarity, motility, and apoptosis. Previous studies have shown positive in vivo results with the use of rho-kinase inhibitors for inhibition of CNV. This study will examine the effect of a widely available rho-kinase inhibitor, Netarsudil ophthalmic solution (0.02%; 0.02 mg/mL), brand name Rhopressa®, on the regression of CNV in a PAX-6 knockout mouse model. Loss of PAX-6 leads to aniridia, a rare condition characterized by congenital iris hypoplasia, foveal hypoplasia and the development of cataract, glaucoma and CNV secondary to limbal stem cell deficiency. Mice will be treated once daily with Netarsudil (treatment) or balanced salt solution (control) for a total of 8-weeks. At the end of the study period, mice will be euthanized for corneal immunostaining (CD31, endothelial vascular marker) to quantify CNV. We hypothesize that the percentage of CNV will be significantly lower in PAX-6 knockout mice cornea treated with Netarsudil ophthalmic solution compared to balanced salt solution. This study has direct clinical relevance as there are currently no commonly used or easily administered treatments for CNV. Results of this study may help to guide future treatment options and research.
StatusActive
Effective start/end date7/1/216/30/22

Funding

  • Illinois Society for the Prevention of Blindness (Basti AGMT 9/7/21)

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