An anti-angiogenic state in mice and humans with retinal photoreceptor cell degeneration.
Abnormal angiogenesis accompanies many pathological conditions including cancer, inflammation, and eye diseases. Proliferative retinopathy because of retinal neovascularization 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. Here 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. 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, although other growth factors may also be involved. Preventive and therapeutic strategies against both proliferative and degenerative retinopathies may emerge from this work.
Lahdenranta
J
J
University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Pasqualini
R
R
Schlingemann
R O
RO
Hagedorn
M
M
Stallcup
W B
WB
Bucana
C D
CD
Sidman
R L
RL
Arap
W
W
D000818:Animals; D003930:Diabetic Retinopathy / Q000150:complications / Q000473:pathology; D016228:Endothelial Growth Factors / Q000235:genetics; D006801:Humans; D008222:Lymphokines / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009389:Neovascularization, Pathologic / Q000473:pathology*; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology*; D012160:Retina / Q000473:pathology; D012171:Retinal Vessels / Q000473:pathology*; D012174:Retinitis Pigmentosa / Q000150:complications / Q000473:pathology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors