Inhibition of experimental choroidal neovascularization in rats by an alpha(v)-integrin antagonist.
OBJECTIVE
Integrin alpha(v)beta3 is predominantly expressed on endothelial cells in choroidal neovascularization (CNV). We evaluated the efficacy of cyclic RGD (Arg-Gly-Asp) peptide, an alpha(v)-integrin antagonist, in a rat model of laser-induced CNV METHODS: We evaluated the effect of cyclic RGD on the adhesion and cell viability of bovine choroidal endothelial cells (BCECs) by cell counting and the trypan blue dye exclusion test. CNV was induced by laser photocoagulation in female Long Evans rats (day 0), followed by intravitreal administration of one dose of cyclic RGD of 200 (n = 9), 100 (n = 10), 50 (n = 4), or 0 microg (n = 9) on days 9 and 11. We assessed the area of CNV by fluorescein angiography and the thickness microscopically on histologic sections. Neovascular vessels were detected by an antibody against factor VIII.


RESULTS
Cyclic RGD (0.02 to 200 microg/ml) inhibited adhesion of BCECs in a dose-dependent manner without changing the cell viability (p < 0.01). In eyes treated with two injections of 200 or 100 microg of cyclic RGD peptide, the development of CNV was significantly (p < 0.01) inhibited in the area of leakage on fluorescein angiography. Histologically, the CNV membrane was observed beneath the retina and the factor VIII-positive cells and red blood cells were involved. The thickness of the lesions was significantly (p < 0.01) reduced in eyes that received 200 or 100 microg of RGD.


CONCLUSIONS
Cyclic RGD effectively inhibited CNV progression in a rat model of laser-induced CNV, suggesting that this alpha(v)-integrin antagonist may be beneficial in the treatment of CNV.
Department of Ophthalmology, Faculty of Medicine, Leipzig University, Leipzig, Germany.
Tsutomu
T
Yasukawa
Stefan
S
Hoffmann
Wolfram
W
Eichler
Ulrike
U
Friedrichs
Yu-Sheng
YS
Wang
Peter
P
Wiedemann
D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D002829:Choroid / Q000098:blood supply; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D005451:Fluorescein Angiography; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D023421:Models, Animal; D009842:Oligopeptides / Q000627:therapeutic use*; D051381:Rats; D020318:Rats, Long-Evans
D039302:Integrin alphaVbeta3; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid