Degree
Master of Science
Program
Pathology
Supervisor
Dr. Sunil K. Parapuram
Abstract
Glaucoma is a multifactorial condition caused, in part, by fibrosis of the sieve-like trabecular meshwork (TM) tissue, which impedes drainage of aqueous humor (AH), leading to increased intraocular pressure and associated optic nerve damage and blindness. Fibrosis of the TM is mainly caused by the increased levels of active transforming growth factor-β 2 (TGFβ2) in the AH of glaucoma patients.
Previous reports have shown that TGFβ decreases the expression of Phosphatase and Tensin Homolog (PTEN) gene and that PTEN is a major regulator of ECM deposition. In this study we investigate the regulation of PTEN protein expression and activity by TGFβ2 in TM cells to determine the mechanism by which excess ECM is deposited.
Here we show that TGFβ2 induces collagen deposition in TM cells by phosphorylation of PTEN, a mechanism that is known to inactivate PTEN. Phosphorylation of PTEN by TGFβ is novel and has not been previously reported. We have found that PTEN protein expression and phosphorylation is regulated by the PI3 kinase pathway. We further show that transfection of TM cells to express enhanced-active PTEN decreases TGFβ2-induced deposition of collagen type I (COL1) protein. Thus, regulation of PTEN activity could serve as a therapeutic target with high potential to prevent excess ECM deposition in the TM of glaucoma patients.
Recommended Citation
Tellios, Nikoleta, "Regulation of Phosphatase and Tensin Homolog Expression and Activity by Transforming Growth-Factor Beta in the Trabecular Meshwork Cells: Implications for Primary Open Angle Glaucoma" (2016). Electronic Thesis and Dissertation Repository. 3832.
https://ir.lib.uwo.ca/etd/3832
Included in
Laboratory and Basic Science Research Commons, Medical Cell Biology Commons, Molecular Biology Commons, Ophthalmology Commons