An Anti-angiogenic State in Mice and Humans with Retinal Photoreceptor Cell Degeneration

Abstract

Abstract: : Purpose: Proliferative retinopathy is a leading cause of blindness in developed countries. Another major cause of irreversible vision loss is retinitis pigmentosa, a group of diseases characterized by progressive photoreceptor cell degeneration. Interestingly, anecdotal evidence has long suggested that proliferative diabetic retinopathy is rarely associated clinically with retinitis pigmentosa. Methods: Mice with classic inherited retinal degeneration (Pdeb rd1 /Pdeb rd1 )were studied in a model of oxygen-induced proliferative retinopathy Results: We show that neonatal mice with classic inherited retinal degeneration (Pdeb rd1 /Pdeb rd1 ) fail to mount reactive retinal neovascularization in a mouse model of oxygen-induced proliferative retinopathy. We also present a comparable human paradigm: spontaneous regression of retinal neovascularization associated with long-standing diabetes mellitus occurs when retinitis pigmentosa becomes clinically evident. Conclusions: Both mouse and human data indicate that reactive retinal neovascularization either fails to develop or regresses when the number of photoreceptor cells is markedly reduced. Our findings support the hypothesis that a functional mechanism underlying this anti-angiogenic state is failure of the predicted up-regulation of vascular endothelial growth factor. Preventive and therapeutic strategies against both proliferative and degenerative retinopathies may emerge from this work.

Keywords: retinal neovascularization • diabetic retinopathy • retinal degenerations: cell biology