Attenuation of retinal vascular development and neovascularization during oxygen-induced ischemic retinopathy in Bcl-2-/- mice.
Bcl-2 is a death repressor that protects cells from apoptosis mediated by a variety of stimuli. Bcl-2 expression is regulated by both pro- and anti-angiogenic factors; thus, it may play a central role during angiogenesis. However, the role of bcl-2 in vascular development and growth of new vessels requires further delineation. In this study, we investigated the physiological role of bcl-2 in development of retinal vasculature and retinal neovascularization during oxygen-induced ischemic retinopathy (OIR). Mice deficient in bcl-2 exhibited a significant decrease in retinal vascular density compared to wild-type mice. This was attributed to a decreased number of endothelial cells and pericytes in retinas from bcl-2-/- mice. We observed, in bcl-2-/- mice, delayed development of retinal vasculature and remodeling, and a significant decrease in the number of major arteries, which branch off from near the optic nerve. Interestingly, hyaloid vessel regression, an apoptosis-dependent process, was not affected in the absence of bcl-2. The retinal vasculature of bcl-2-/- mice exhibited a similar sensitivity to hyperoxia-mediated vessel obliteration compared to wild-type mice during OIR. However, the degree of ischemia-induced retinal neovascularization was significantly reduced in bcl-2-/- mice. These results suggest that expression of bcl-2 is required for appropriate development of retinal vasculature as well as its neovascularization during OIR.
Wang
Shoujian
S
Department of Ophthalmology and Visual Sciences, University of Wisconsin Medical School, Madison, WI 53792-4673, USA.
Sorenson
Christine M
CM
Sheibani
Nader
N
D000375:Aging; D000818:Animals; D002455:Cell Division; D019254:Genes, bcl-2; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000473:pathology*; D010100:Oxygen / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012164:Retinal Diseases / Q000473:pathology*; D012171:Retinal Vessels / Q000473:pathology*
D019253:Proto-Oncogene Proteins c-bcl-2; D010100:Oxygen