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.
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| Quiroz, Yakeel T; Schultz, Aaron P; Chen, Kewei et al. (2015) Brain Imaging and Blood Biomarker Abnormalities in Children With Autosomal Dominant Alzheimer Disease: A Cross-Sectional Study. JAMA Neurol 72:912-9 |
| Arboleda-Velasquez, Joseph F; Primo, Vincent; Graham, Mark et al. (2014) Notch signaling functions in retinal pericyte survival. Invest Ophthalmol Vis Sci 55:5191-9 |
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