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Type of Document Dissertation Author Suarez, Sandra Author's Email Address sandrasuarez4@gmail.com URN etd-12052015-165628 Title An Investigation of the GAPDH/Siah1 Pathway in Human Retinal Pericyte Apoptosis Degree PhD Department Cell and Developmental Biology Advisory Committee
Advisor Name Title John J. Reese Committee Chair David M. Miller Committee Member Douglas G. McMahon Committee Member John S. Penn Committee Member Sandra S. Zinkel Committee Member Keywords
- Diabetic retinopathy
- cell death
- apoptosis
- high glucose
- GAPDH
- Siah1
- cell signaling
Date of Defense 2015-12-04 Availability unrestricted Abstract Diabetic Retinopathy (DR) is a leading cause of blindness worldwide, and its prevalence is growing. Current therapies for DR address only the later stages of the disease, are invasive and are of limited effectiveness. Retinal pericyte death is an early pathologic feature of DR. Though it has been observed in diabetic patients and in animal models of DR, the cause of pericyte death remains unknown. A novel pro-apoptotic pathway initiated by the interaction between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the E3 ubiquitin ligase, seven in absentia homolog 1 (Siah1), was identified to play a significant role in human retinal pericyte apoptosis. Inhibition of the GAPDH/Siah1 pro-apoptotic complex blocks diabetes-induced pericyte apoptosis, widely considered a hallmark feature of DR.Files
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