Compositions and Methods for Treating Diabetic Eye Disease

Joslin Diabetes Center, Inc.
posted on 03/09/2009

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Diabetic retinopathy (DR) is the leading cause of vision loss in working adults. 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. Increased retinal vascular permeability (RVP) is a primary cause of diabetic macular edema and a characteristic finding in PDR. The onset of PDR and diabetic macular edema is thought to result from a change in the balance between pro-angiogenic/permeability factors and anti-angiogenic/permeability factors. Functional proteomics was used to identify novel factor(s) that contribute to the changes observed in the eye associated with diabetes. Such changes include excessive vascular permeability or vascularisation of the eye, e.g., associated with diabetic retinopathy, proliferative diabetic retinopathy, or diabetic macular edema. These studies revealed a number of proteins whose expression levels are altered in PDR and/or macular edema. Among these is one specific protein, a member of a well-studied signaling pathway, the concentrations of which are reduced with diabetes. The lowered levels of this protein appear to reduce inhibition of angiogenesis and permeability and thus allow complications to arise. It is therefore believed that this protein plays a regulatory role in mediating retinal complications of diabetes. The invention features methods of treating retinal vascularisation or vascular permeability in the eye, by administering this protein or peptide fragments thereof, or by administering agents that increase the concentrations of this protein in the eye. This protein has never before been identified as being involved in diabetes or its complications, and therefore represents a new therapeutic target.