Date of Award

12-1-2014

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Field of Study

Biomedical Sciences

Department

Graduate School of Biomedical Sciences

First Advisor

Patrick R. Cammarata

Abstract

The human lens epithelium thrives in a naturally hypoxic environment resisting mitochondrial depolarization, a precursor of apoptosis. The ability of the lens to resist mitochondrial depolarization is referred to as lenticular mitoprotection and is rendered by a sustained synthesis of the pro-survival Vascular Endothelial Growth Factor (VEGF). Similar lenticular mitoprotective pathways come in to play when the hypoxic lens epithelium is exposed to atmospheric oxygen during ocular surgeries like the cataract surgery. Posterior capsular opacification (PCO) is a complication of cataract surgery resulting from the mesenchymal transition of the epithelial cells. The lenticular mitoprotective pathways involved in lens epithelial cell survival also initiate the mesenchymal transition of the epithelial cells, thus contributing to the pathogenesis of PCO. The progression of PCO involves the initiation phase in atmospheric oxygen (during the cataract surgery) and a persistence phase (persistence of the insult which occurred during cataract surgery) in hypoxia. The initial insult to epithelial cells occurs in atmospheric oxygen initiating the mesenchymal transition which persists when the lens epithelium is back in hypoxia after the surgery. Isolating the two events of lenticular mitoprotection and mesenchymal would be a beneficial therapeutic target. The data presented in this study supports a model whereby the onset of epithelial to mesenchymal transition may circuitously benefit from the enhanced synthesis of the pro-survival factor VEGF. As a result of which a mesenchymal cell resisting mitochondrial depolarization is generated, leading to the progression of PCO. The findings in this study support the possibility of generating a therapeutic target such that the mesenchymal transition of normal epithelial cells can be prevented without affecting the levels of pro-survival VEGF and compromising the lenticular mitoprotective pathways.

Comments

Neelam,Sudha, The Disadvantageous Interrelationship between Lenticular Mitoprotection and Epithelial-Mesenchymal transition via Nuclear Beta catenin. Doctor of Philosophy (Biomedical Sciences), November, 2014, 120 pp., 33 illustrations, bibliography, 100 titles. Available worldwide, December 2015

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