Diagnosing and Treating Diabetic Retinopathy
Description: Diabetic retinopathy (DR) is the leading cause of vision loss in working adults. Although its incidence and progression can be reduced by intensive glycemic and blood pressure control, nearly all patients with type 1 diabetes mellitus and over 60% of those with type 2 diabetes eventually develop retinal microvascular abnormalities, and 20% to 30% of these patients advance to active proliferative diabetic retinopathy (PDR) and/or diabetic macular edema. Although surgical options exist, developing preventative treatments for these disorders remains a major unmet clinical need. Increased retinal vascular permeability (RVP) is a primary cause of diabetic macular edema and a characteristic finding in PDR. Several reports in the literature support the concept that vitreous fluid contains proteins that correlate with specific retinal pathologies, and that proteins in the vitreous compartment affect retinal vascular functions. Using mass spectroscopy–based proteomics which detected 117 proteins in human vitreous fluid, the inventors found elevated levels of extracellular carbonic anhydrase-I (CA-I) in vitreous from individuals with diabetic retinopathy, suggesting that retinal hemorrhage and erythrocyte lysis contribute to the diabetic vitreous proteome. Intravitreous injection of CA-I in rats increased retinal vessel leakage and caused intraretinal edema. CA-I–induced retinal edema was decreased by administration of several compounds known to inhibit this enzyme. Subdural infusion of CA-I in rats induced cerebral vascular permeability, suggesting that extracellular CA-I could have broad relevance to neurovascular edema. Inhibition of extracellular CA-I could provide new therapeutic opportunities for the treatment of hemorrhage-induced retinal and cerebral edema. Clinical & Commercial Utility: The invention features methods of treating diabetic retinopathy by reducing retinal vascular permeability in the eye, through administration of inhibitors of CA-I. Inhibition of CA-I might also be used to treat other conditions such as hemorrhage-induced retinal and cerebral edema. The invention also features methods of diagnosing diabetic retinopathy by detecting CA-I and other proteins known to be overly abundant in the vitreous in the disease state.U.S. and European patent applications claiming this invention have been filed. The research underlying this invention has been published, in Gao et al. Nature Medicine 13, 181–188 (2007).
Type of Offer: Licensing
« More Medical Patents