Notch and TGF-beta in the Control of Retinal Vascular Integrity

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ABSTRACT 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.