Chiara Gerhardinger

The focus of my laboratory is the pathogenesis of diabetic retinopathy one of the leading causes of blindness in the adult population of the United States. Future projections indicate that diabetic retinopathy will only worsen as a public health problem, as the prevalence of diabetes increases due to the current obesity epidemics and population aging. The only therapeutic intervention proven to delay the onset and progression of diabetic retinopathy is the primary treatment of diabetes to achieve near-euglycemia. However, tight metabolic control is not easy to achieve, and intensive insulin therapy is not always practical and free of complications. To preserve visual function in diabetes, we need to develop adjunct treatments that target the consequences of suboptimal metabolic control at the early stages of disease development before the occurrence of irreversible vascular damage. In order to develop such treatments, there is a crucial need for a better understanding of the mechanisms linking the diabetic milieu to retinal vascular damage.

To identify the pathogenetic pathways that could become therapeutic targets to prevent diabetic retinopathy, we have recently studied the gene expression profile of retinal Müller glial cells –an early target of diabetes in the retina—and retinal microvessels –the clinically relevant retinal target of diabetes. The results of these studies indicate that a common effect of diabetes on retinal glial and vasculature is the upregulation of several acute-phase response proteins and other inflammation related genes, a process accompanied by the induction of the proinflammatory cytokine interleukin-1beta (IL-1beta]) in the retina. Upregulation of IL-1beta and acute-phase proteins in the retina occurs early in the course of diabetes and precedes the development of vascular cell apoptosis. Because many of the molecular, cellular, and functional abnormalities known to occur in the retina in diabetes correspond to known biological effects of IL-1beta, I hypothesize that the retinal upregulation of IL-1beta-- leading to glial activation and endothelial dysfunction -- is a major contributor to the development of diabetic retinopathy. The current goals are to understand how diabetes leads to the inflammatory response of the glial and vascular components of the retina, and to determine whether inflammatory changes and especially IL-1beta have a causal role in the development of retinopathy. Identifying IL-1beta as a mediator of diabetes-induced retinal damage would have a profound impact on the field of diabetic retinopathy, opening new avenues for the prevention and treatment of this complication of diabetes.