Susanne Mohr

Assistant Professor

Ph.D., University of Konstanz
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Identifying mechanisms underlying the development of diabetic retinopathy

RESEARCH DESCRIPTION

Diabetic retinopathy is today the leading cause of acquired blindness among young adults. The background stages of diabetic retinopathy are believed to lead to the advanced, sight-threatening stages of the retinopathy as a result of a progressive decrease in perfusion of the retinal vasculature and resulting ischemia of the retina. Histologic analysis of retinal areas that were non-perfused in vivo has indicated that non-perfused vessels are acellular. How the capillary cells die is unclear, but both retinal capillary pericytes and endothelial cells have been found to die by a process consistent with apoptosis in diabetic humans and diabetic animals and in experimental galactosemia (another model that develops a diabetic-like retinopathy). Capillary cells are not the only retinal cells undergoing apoptotic cell death in diabetes. A greater than normal frequency of non-vascular cells, seemingly Müller (glial) cells and ganglion cells, also have been reported to become TUNEL-positive in retinas of diabetic humans and animals. Caspases, a family of cysteine proteases, are known to be critically involved in two activities: activation of pro-inflammatory cytokines, and the initiation and execution of apoptosis. Our results have shown that activities of cas-1 family members and other caspases are increased in the retinas of mice at 2 months, and remained elevated over 8 months of diabetes compared to normal. Increased caspase activation could be confirmed in retinas of diabetic humans.

Therefore, we are interested in: (1) what role do caspases play in the development of diabetic retinopathy, (2) how does hyperglycemia activate caspases and are there cell type specific caspase signaling pathways, (3) is caspase-1 involved in inflammatory processes or does it act as an apoptosis initiator, and (4) are caspases suitable as therapeutical targets. Experiments are conducted in vivo and in vitro using diabetic and galacosemic mice, human tissue, cultured retinal endothelial and Müller cells.

RELATED RESEARCH AREAS

View Susanne Mohr's Publications on PubMed