Diabetic retinopathy is among the most common complications of diabetes. Basement membrane thickening and pericyte loss are early changes associated with the development of diabetic retinopathy. I speculate that these events disrupt Notch signaling, which depends upon juxtaposition of cellular membranes, and also impair cell signaling cross-talk between Notch and TGF-? signaling. To test this hypothesis, I propose to: (i) establish a cell culture system to measure cell-cell interactions mediated by Notch using imaging methods;(ii) examine how Notch/TGF-? signaling is affected in vascular cells cultured under conditions resembling a diabetic environment;and, (iii) use mouse models and postmortem human eye tissue for examining the role of Notch/TGF- ? interactions in diabetic retinopathy. I propose a training plan that will enable me to accomplish the proposed experiments and a strategy for transition towards career independence.

Public Health Relevance

In this research proposal I propose to test the hypothesis that a signaling pathway termed Notch plays a role in the development of diabetic retinopathy, which is a prevalent cause of vision loss. I propose a training plan that will allow me to study this problem using cell culture systems and in vivo models of diabetes.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Transition Award (R00)
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Special Emphasis Panel (NSS)
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Liberman, Ellen S
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Schepens Eye Research Institute
United States
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