Truncated netrin-1 contributes to pathological vascular permeability in diabetic retinopathy.

ABSTRACT: Diabetic retinopathy (DR) is a major complication of diabetes and a leading cause of blindness in the working-age population. Impaired blood-retinal barrier function leads to macular edema that is closely associated with the deterioration of central vision. We previously demonstrated that the neuronal guidance cue netrin-1 activates a program of reparative angiogenesis in microglia within the ischemic retina. Here, we provide evidence in both vitreous humor of diabetic patients and in retina of a murine model of diabetes that netrin-1 is metabolized into a bioactive fragment corresponding to domains VI and V of the full-length molecule. In contrast to the protective effects of full-length netrin-1 on retinal microvasculature, the VI-V fragment promoted vascular permeability through the unc

SUBMITTER: Miloudi K 

PROVIDER: S-EPMC4966311 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature