Diagnosing and Treating Retinal Vascular Permeability

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

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. Functional proteomics was used to identify novel factors that contribute to the excessive increase in RVP that is observed in PDR. The effect of diabetic retinopathy on the vitreous proteome was characterized by comparing the vitreous protein composition of nondiabetic subjects and diabetic patients with or without active PDR. These studies revealed a number of proteins in a well-known pathway whose levels are elevated in PDR, which might therefore be targets for drug development against diabetic retinopathy. In addition, it was discovered that RVP is associated with an increased (more alkaline) pH, so that manipulation of the pH of the vitreous might also be a useful therapeutic tool. The invention features methods of treating diabetic retinopathy by reducing retinal vascular permeability in the eye, through administration of inhibitors of the proteins in this pathway, or by manipulating the pH of the vitreous. The invention also features methods of diagnosing diabetic retinopathy by detecting the proteins known to be overly abundant in the vitreous in the disease state.