Pro-angiogenic Effect of Human Origin RGD Motif: Inhibition of Suppressed Retinal Neovascularization and Vessel Leakage Induced by Oxygen Induced Retinopathy

Abstract

Purpose:: It was reported snake venom origin RGD motif trigger normalization of retinal vasculature in our previous studies. We suppose that use of human origin RGD motifs have more advantages of snake venom origin RGD motif in application onto the therapeutics of eye related diseases. Therefore, this study was objected to verify the pro-angiogenic effects of human RGD motif derives in oxygen induced retinopathy (OIR) mouse model and the functional condition of them.

Methods:: EGTs, 6-7 kDa of recombinant human RGD polypeptide and its modifications, were obtained from Yonsei University. OIR mouse model was allowed to verify new effect of EGTs. New born mice induced retinopathy by hyperoxia was treated with 10 uM of EGTs. The retinas were stained with FITC-dextran to observe vessel morphology and others were HE-stained to verify micro-pathological changes. EGTs were applied into mouse corneal micropocket assay to investigate relation to VEGF in its functional condition. Mice were implanted the pellet with or without VEGF in the corneal pocket and treated with 10 uM of EGTs. Corneal neovascularization was qualitatively and quantitatively evaluated compared with a sham.

Results:: It was observed decrease of hemorrhages, retinal abnormal vessels and ischemic lesions, and morphological normalization of retinal vessel networks by administration of EGTs in the assay using OIR mouse model and fluorescence angiogram. However, density of vessel network around an optic disk was insufficient compared with a normal in spite of EGTs treatment. The thickness of ganglion cell layer was also changed thin like a normal. In corneal micropocket assay, no neovascularization was observed in cornea implanted pellet containing only vehicle in spite of EGTs treatment. However, neovascularization from corneal limbus was obviously induced in the groups implanted pellets containing VEGF irrespective of treatments. The length of new vessels in VEGF containing pellets implanted groups was significantly increased compared with the mice implanted pellets without VEGF.

Conclusions:: This result shows that EGTs prevent the suppression of retinal blood vessel formation in the ischemic mouse model and inhibit vessel leakages. Therefore, we supposed that human origin RGD motif may be used as a new drug candidate on therapy of eye related diseases, and would have more advantages in clinical application because of its originality.

Keywords: neovascularization • retinopathy of prematurity • ischemia