An anti-angiogenic state in mice and humans with retinal photoreceptor cell degeneration

Abnormal angiogenesis accompanies many pathological conditions including ca ncer, inflammation, and eye diseases. Proliferative retinopathy because of retinal neovascularization is a leading cause of blindness in developed cou ntries. Another major cause of irreversible vision loss is retinitis pigmen tosa, a group of diseases characterized by progressive photoreceptor cell d egeneration. Interestingly, anecdotal evidence has long suggested that prol iferative diabetic retinopathy is rarely associated clinically with retinit is pigmentosa. Here we show that neonatal mice with classic inherited retin al degeneration (Pdeb(rd1)/Pdeb(rd1)) fail to mount reactive retinal neovas cularization in a mouse model of oxygen-induced proliferative retinopathy. We also present a comparable human paradigm: spontaneous regression of reti nal neovascularization associated with long-standing diabetes mellitus occu rs when retinitis pigmentosa becomes clinically evident. Both mouse and hum an data indicate that reactive retinal neovascularization either fails to d evelop or regresses when the number of photoreceptor cells is markedly redu ced. Our findings support the hypothesis that a functional mechanism underl ying this anti-angiogenic state is failure of the predicted up-regulation o f vascular endothelial growth factor, although other growth factors may als o be involved. Preventive and therapeutic strategies against both prolifera tive and degenerative retinopathies may emerge from this work.