Abstract
Abstract: :
Purpose: Bcl–2 is a death repressor and protects cells from apoptosis induced by a variety of stimuli. Its activity has been demonstrated to be central to promotion and inhibition of angiogenesis by many angiogenic and anti–angiogenic factors. This report investigates the physiological role of bcl–2 in postnatal vascularization of retina and retinal neovascularization during oxygen–induced ischemic retinopathy. Methods: The retinal vascular density was determined in wild type and bcl–2 –/– mice using retinal trypsin digests. Development of retinal vasculature was assessed at different time points using PECAM–1 staining of wholemount and frozen sections of retina prepared from wild type and bcl–2 –/– mice. The degree of proliferation and apoptosis were determined using Brdu and TdT–dUTP TUNEL labeling of wholemount retinas, respectively. Retinal neovascularization in oxygen–induced ischemic retinopathy was assessed by PECAM–1 staining of wholemount retinas and counting of vascular cell nuclei in retinal serial sections. Results: Bcl–2 –/– mice exhibited reduced retinal vascular density compared to wild type mice. We observed a significant decrease in the number of endothelial cells and pericytes in bcl–2 –/– mice retinas. This was concomitant with a significant increase in the rate of proliferation and apoptosis of vascular cells in bcl–2 –/– retinas. Bcl–2 –/– retinas also exhibited a significant decrease in the number of major arteries and veins branching from the optic nerve. PECAM–1 staining of wholemount retinas during retinal vascularization demonstrated a significant delay in development and maturation of retinal vasculature in bcl–2 –/– mice. The bcl–2 –/– mice were severely compromised in their ability to elicit a neovascular response during oxygen–induced ischemic retinopathy. Conclusion: Bcl–2 expression is essential for appropriate development of retinal vasculature and its neovascularization during oxygen–induced ischemic retinopathy. Therefore, bcl–2 may provide a suitable target for treatment of retinopathy of prematurity, as well as other diseases with a neovascular component.
Keywords: retinal neovascularization • cell death/apoptosis • retinopathy of prematurity