Crosstalk Between Transforming Growth Factor Beta-2 and Toll-Like Receptor 4 in the Trabecular Meshwork

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dc.contributor.advisorMcDowell, Colleen
dc.contributor.committeeMemberClark, Abbot F.
dc.contributor.committeeMemberPang, Iok-Hou
dc.creatorHernandez, Humberto
dc.date.accessioned2019-08-22T21:49:13Z
dc.date.available2019-08-22T21:49:13Z
dc.date.issued2017-12-01
dc.date.submitted2018-05-22T12:18:08-07:00
dc.description.abstractThe trabecular meshwork (TM) is the main site of outflow resistance in primary-open angle glaucoma (POAG) patients. In these patients, aqueous humor outflow resistance increases, subsequently leading to a rise in intraocular pressure (IOP). The rise in IOP ultimately damages the optic nerve and leads to blindness. Accumulation of extracellular matrix (ECM) at the TM has been shown by our laboratory and many others to be responsible for the increase in outflow resistance. The molecular mechanisms underlying the pathology are beginning to be elucidated. The pro-fibrotic cytokine, transforming growth factor beta-2 (TGFβ2), has been shown to be elevated in the aqueous humor of POAG patients. Mice injected with adenovirus encoding active TGFβ2 develop ocular hypertension and ECM deposition at the TM. Recently, toll-like receptor 4 (TLR4) signaling has been linked to the development of fibrosis. In our studies, we evaluated the crosstalk between TGFβ2 and TLR4 in the TM. We utilized in vitro and in vivo models to evaluate the role of TLR4 on the production of ECM and development of ocular hypertension. We also utilized a conditional knockout in vitro and in vivo adenovirus delivery system to study BMP and Activin Membrane Bound Inhibitor (BAMBI), a critical molecule in the crosstalk between TGFβ2 and TLR4. Our studies reveal a novel pathway involved in the development of TM damage and potential targets to lower IOP.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29606
dc.language.isoen
dc.provenance.legacyDownloads8
dc.subjectMedical Sciences
dc.subjectMedicine and Health Sciences
dc.subjectTGFb2
dc.subjectTLR4
dc.subjectBAMBI
dc.subjectBMP
dc.subjecttrabecular meshwork
dc.subjectocular hypertension
dc.subjectECM
dc.titleCrosstalk Between Transforming Growth Factor Beta-2 and Toll-Like Receptor 4 in the Trabecular Meshwork
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineVisual Sciences
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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