The Urokinase Receptor-Derived Peptide UPARANT as a novel therapy to recover high glucose-associated retinal damage in spontaneously diabetic Torii rats

Spontaneously diabetic Torii (SDT) rats are an inbred strain of rats with a non-obese type 2 diabetes mellitus that were isolated from an outbred colony of Sprague–Dawley (SD) rats. They develop diabetes mellitus at about 20 weeks of age and, about 24 weeks later, are characterized by alterations of electroretinogram (ERG) and blood retinal barrier (BRB) dysfunction followed by later proliferative neovascularization. SDT rats are a useful model to investigate possible therapeutical approaches that may counteract the pathological signs of diabetic retinopathy (DR). The urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) system is up-regulated in rat models of DR and treatments downregulating this system may have some effects. We tested the possibility that systemic administration of UPARANT, a highly resistant peptide inhibitor of the uPA/uPAR system, might prevent visual dysfunction and BRB leakage in SDT rats