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.
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.
|Primo, Vincent A; Arboleda-Velasquez, Joseph F (2016) Isolation and Transfection of Primary Culture Bovine Retinal Pericytes. Methods Mol Biol 1430:107-17|
|Arboleda-Velasquez, Joseph F; Valdez, Cammi N; Marko, Christina K et al. (2015) From pathobiology to the targeting of pericytes for the treatment of diabetic retinopathy. Curr Diab Rep 15:573|