CYP1B1 Deficient Mice Exhibit Reduced Retinal Vascular Density and Fail to Respond to Hypoxia-Induced Neovascularization

Abstract

Abstract: : Purpose: Mutations in the cyp1b1 gene is linked to development of congenital glaucoma in humans. Although, cyp1b1 has been shown to be expressed at different ocular sites its role in ocular development and its normal function remains largely unknown. This report investigates the role of cyp1b1 in retinal vascular development and hypoxia-induced neovascularization. Methods: Retinal vascular density was assessed in wild type and cyp1b1-/- mice during development by determining the number of endothelial cells and pericytes in retinal trypsin digests. Retinal neovascularization in oxygen-induced ischemic retinopathy was assessed by PECAM-1 staining of retina wholemounts and determining the number of endothelial cell nuclei in retinal serial sections. Results: The retinal trypsin digests indicated that the ratio of endothelial cells to pericytes was lower in three- and six-weeks old cyp1b1-/- mice compared to wild type mice. Therefore, the retinal vascular density of cyp1b1-/- mice is significantly lower than of the wild type mice. In the oxygen-induced ischemic retinopathy model, cyp1b1-/- mice failed to elicit a neovascularization response during the hypoxic phase. Conclusions: We demonstrate that cyp1b1 is an important modulator of retinal vascular homeostasis and in its absence hypoxia-driven retinal neovascularization is attenuated.

Keywords: retinal neovascularization • hypoxia • retinopathy of prematurity