Bim is responsible for the inherent sensitivity of the developing retinal vasculature to hyperoxia.
Apoptosis plays an important role in development and remodeling of vasculature during organogenesis. Coordinated branching and remodeling of the retinal vascular tree is essential for normal retinal function. Bcl-2 family members, such as bim not only influence apoptosis, but also cell adhesive and migratory properties essential during vascular development. Here we examined the impact of bim deficiency on postnatal retinal vascularization, as well as retinal neovascularization during oxygen-induced ischemic retinopathy (OIR) and laser-induced choroidal neovascularization. Loss of bim expression was associated with increased retinal vascular density in mature animals. This was mainly attributed to increased numbers of pericytes and endothelial cells. However, the initial spread of the superficial layer of retinal vasculature and, the appearance and density of the tip cells were similar in bim+/+ and bim-/- mice. In addition, hyaloid vessel regression was attenuated in the absence of bim. Furthermore, in the absence of bim retinal vessel obliteration and neovascularization did not occur during OIR. Instead, normal inner retinal vascularization proceeded independent of changes in oxygen levels. In contrast, choroidal neovascularization occurred equally well in bim+/+ and bim-/- mice. Together our data suggest bim expression may be responsible for the inherent sensitivity of the developing retinal vasculature to changes in oxygen levels, and promotes vessel obliteration in response to hyperoxia.
Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA.
Shoujian
S
Wang
SunYoung
S
Park
Ping
P
Fei
Christine M
CM
Sorenson
D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D017931:DNA Primers / Q000235:genetics; D018496:Hyperoxia / Q000503:physiopathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000502:physiology*; D038081:Organogenesis / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000196:embryology*; D012171:Retinal Vessels / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A
D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; D017931:DNA Primers; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D001973:Bromodeoxyuridine