Systemic and Periocular Deliveries of Plasminogen Kringle 5 Reduce Vascular Leakage in Rat Models of Oxygen-Induced Retinopathy and Diabetes

PURPOSE: Increased retinal vascular permeability is a common complication of diabetes and a major cause of vision loss in diabetic patients. The current study is to determine the effect of plasminogen kringle 5 (K5) on vascular leakage via systemic and periocular deliveries. METHODS: Oxygen-induced retinopathy (OIR) was generated by exposing newborn rats to 75% oxygen. Diabetes was induced in adult rats by injection of streptozotocin (STZ). Retinal vascular permeability was measured by the Evans blue-albumin leakage method. RESULTS: Subcutaneous, intraperitoneal, subconjunctival, and retrobulbar injections and topical eyedrop application of K5 significantly reduced retinal vascular permeability in both the OIR and STZ-diabetic rat models. Compared with the periocular deliveries, systemic administration requires higher doses of K5. K5 deliveries downregulated VEGF expression in the retina. CONCLUSIONS: K5 can reduce retinal vascular permeability through systemic and periocular deliveries. These delivery routes of K5 have therapeutic potential in the treatment of vascular leakage.