R-Ras in retinal angiogenesis

Purpose R-Ras is a small GTPase belonging to the Ras family of proteins, that regulate cell migration, proliferation and survival. It has been shown to play an important role in vessel maturation. The purpose of this study was to evaluate role of R-Ras in retinal angiogenesis and vascular stability in oxygen induced retinopathy (OIR) model. Methods Immunohistochemistry, confocal microscopy and qPCR we used to study expression pattern of R-Ras in mouse retinas. R-Ras deficient mice were used to study function of R-Ras during retinal angiogenesis. Retinal vascular permeability was measured using Miles assay where Evans blue (EB) dye is injected into circulation whereafter amount of albumin bound EB in retinas is quantified by spectrophotometer. Results R-Ras is expressed in retinal vessels during developmental angiogenesis as well as during pathological angiogenesis in OIR model. In R-Ras deficient mice retinal angiogenesis was enhanced in OIR model compared to wt mice. Furthermore, retinal vascular permeability was significantly enhanced in R-Ras mice compared to wt mice in OIR model suggesting that R-Ras can effectively stabilize unstable retinal vessels and reduce the leakiness. Conclusion R-Ras provides potentially a very interesting new therapeutic target for the treatment of neo-vascular eye diseases.