[Inhibitory effect of RGDS peptide on experimental choroidal neovascularization in a rat model].
OBJECTIVE
To investigate the efficacy and feasibility of RGDS (Arg-Gly-Asp-Ser) peptide (an alpha(nu)-integrin antagonist) in a rat model of laser-induced choroidal neovascularization (CNV).


METHODS
Experimental CNV was induced by laser photocoagulation in Brown Norway rats (50 microm diameter, 0.05 second duration and 525 mw intensity). Phosphate buffered saline (PBS) or 100, 300 microg of RGDS peptide in PBS were being injected intravitreally after laser surgery for 7 days. On the 14th day after photocoagulation, CNV was observed by fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA). The area of CNV by high molecular weight FITC-dextran (MW 2 x 10(6)) for high resolution angiography in RPE-choroid-sclera flat mounts and the thickness microscopically on histologic sections were evaluated. New vessels were detected and quantified by an-antibody against factor VIII. Two eyes from each group were examined by transmission electron microscopy.


RESULTS
In eyes with injections of 300 or 100 microg of RGDS peptide on the 14th day after laser photocoagulation, the development of CNV was significantly (P < 0.01) inhibited showing by RPE-choroid-sclera flat mounts. Histologically, the thickness of the CNV lesions was significantly (P < 0.01) reduced in eyes that received 300 or 100 microg of RGDS peptide injection. Immunoreactivity of factor VIII in CNV showed significant difference (P < 0.01) in eyes injected with RGDS peptide compared with control eyes. The reduction of the area and the thickness of CNV by RGDS peptide were in a dose-dependent manner. No evidence of toxicity was found in retina by transmission electron microscopy in every group.


CONCLUSIONS
RGDS peptide effectively inhibits CNV progression in a rat model of laser-induced CNV, suggesting that this alpha(nu)-integrin antagonist may be beneficial in the treatment of CNV.
He
Hua
H
Department of Ophthalmology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. hhlotus@tom.com
Zhang
Hong
H
Wang
Zhi-tao
ZT
Zhao
Chun-ming
CM
Xiang
Nan
N
D000818:Animals; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage* / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D011914:Rats, Inbred BN; D014822:Vitreous Body
D009842:Oligopeptides; C046617:arginyl-glycyl-aspartyl-serine