Abstract
Purpose :
RhoA and its downstream effector ROCK play an important role in proangiogenic endothelial cell polarity, motility, and apoptosis, which are all processes involved in the development of neovascularization. Previous research has shown the use of inhibitors for both rhoA and ROCK to reduce corneal neovascularization (CNV) in alkali-burn induced mouse models. These studies demonstrate the use of these agents in corneal wound healing. Our study is designed to evaluate the effect of a commercially available rho-kinase inhibitor (Netarsudil) on established CNV in a PAX-6 knockout mouse model as regression of established CNV has the potential for visual improvement.
Methods :
PAX-6 knockout mice are characterized by congenital iris hypoplasia, foveal hypoplasia and the development of CNV secondary to limbal stem cell deficiency, similar to PAX-6 aniridia in ophthalmic patients. 8 mice (16 eyes) will be divided into two treatment (8 eyes) and a placebo group (8 eyes). The study group is treated with Netarsudil ophthalmic solution (0.02 mg/mL). The placebo group is treated with balanced saline solution. Mice are randomized to be treated once daily or twice daily in one eye, with the opposite eye serving as the placebo. At the start of treatment, anterior segment photography is taken to document baseline CNV. Treatment lasts four weeks. At the end of treatment, mice will be euthanized for corneal immunostaining to quantify CNV.
Results :
Two PAX-6 knockout mice are currently undergoing treatment. Two-week treatment results with slit lamp photography show significant CNV and opacification in both the treatment and control eyes (Figure 1). Ongoing treatment with additional mice as the colony grows will continue for 8 mice, based on a power analysis of a 20% expected decrease. The final outcome is percent area of CNV on corneal immunostaining.
Conclusions :
This pilot study is designed to evaluate whether inhibition of rho-kinase using a topical, commercially available treatment can regress established CNV in an in vivo mouse model. Final results have the potential to impact future research directions for treatment of CNV.
This is a 2021 ARVO Annual Meeting abstract.