Blood Vessel Maturation by Disintegrin in Oxygen-Induced Retinopathy

Abstract

Purpose: Although Arg-Gly-Asp (RGD) motif-containing disintegrins are associated with integrin inhibition and the activation of various biological processes, little is known about the role of RGD motif-containing disintegrin in vascular development and remodeling. We therefore investigated the role of RGD-containing disintegrin in vascular remodeling in oxygen-induced retinopathy (OIR) mouse model. Materials and methods: EGT022, an RGD-containing disintegrin originated from human a disintegrin and metalloproteinase 15 (ADAM15), was used to investigate the role of the disintegrin in vascular development in OIR mouse model. To analyze the functional effects of EGT022 on retinal vascular development, the immunohistochemistry on mouse retinas after fluorescein isothiocyanate (FITC) perfusion was conducted and the vessel integrity was examined using modified Mile's permeability assay. Results: EGT022 was able to reduce overall retinopathy scores by 75%, indicating its efficacy in retinal microvessel maturation stimulation. Pericyte coverage was greatly stimulated by EGT022 treatment in OIR mouse model. EGT022 was also effective to significantly improve blood vessel integrity. Conclusions: RGD-containing disintegrin EGT022 stimulated vascular maturation in OIR mouse model. Experimental results suggest that EGT022 is useful for treatments to improve ischemia in nonproliferative diabetic retinopathy (NPDR), the early stage of diabetic retinopathy.