Rapamycin reduces VEGF expression in retinal pigment epithelium (RPE) and inhibits RPE-induced sprouting angiogenesis in vitro.
Anti-VEGF treatment has become accepted first-line treatment for choroidal neovascularisation (CNV) in age-related macular degeneration. However, VEGF-inhibition does not always lead to sustained CNV-reduction. In this study, the effect of rapamycin was superior to VEGF-inhibition in a co-culture assay of endothelial cells (ECs) and retinal pigment epithelium (RPE). Rapamycin reduced EC sprouting in groups that did not respond to anti-VEGF treatment. Rapamycin did not induce EC apoptosis, but reduced both VEGF-production in RPE and the responsiveness of ECs to stimulation. Rapamycin might therefore be a therapeutic option for CNV patients that do not respond sufficiently to the established anti-VEGF treatments.
Stahl
A
A
Cell Biology Laboratory, University Eye Hospital Freiburg, Germany Killianstrasse 5, 79106 Freiburg, Germany.
Paschek
L
L
Martin
G
G
Gross
N J
NJ
Feltgen
N
N
Hansen
L L
LL
Agostini
H T
HT
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D017209:Apoptosis; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000378:metabolism*; D018920:Coculture Techniques; D006801:Humans; D010857:Pigment Epithelium of Eye / Q000098:blood supply* / Q000378:metabolism*; D020123:Sirolimus / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D020123:Sirolimus