ADAM19 and ADAMTS4 expression in Human Optic Nerve Head Astrocytes

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dc.contributor.advisorTovar-Vidales, Tara
dc.contributor.committeeMemberInman, Denise
dc.contributor.committeeMemberRosales, Armando
dc.creatorEaso, Tony
dc.date.accessioned2024-08-22T19:55:06Z
dc.date.available2024-08-22T19:55:06Z
dc.date.issued2024-05
dc.description.abstractSummary: Glaucoma is characterized by the degeneration and death of retinal ganglion cells (RGCs) and their axons, causing irreversible blindness. Various risk factors contribute to glaucoma onset, including intraocular pressure (IOP), age, and family history (1). In glaucoma, the primary site of damage is the optic nerve head (ONH), specifically the lamina cribrosa (LC) region. The ONH undergoes significant stress and structural changes in response to elevated IOP, leading to the death of RGCs (2). ONH astrocytes, a major cell type in the LC, are believed to play a significant role in the pathological remodeling of the extracellular matrix (ECM) during glaucoma. These cells respond notably to biomechanical stresses and increased levels of the fibrotic cytokine transforming growth factor beta 2 (TGFβ2), which is commonly found in the aqueous humor, trabecular meshwork, and optic nerve head (ONH) of glaucoma patients (2). Our lab has previously shown that ONH tissues treated with TGFβ2 show an increase in proteins that could be involved in glaucoma pathology. In this study, we primarily investigated the expression and regulation by TGFβ2 of A Disintegrin and Metalloproteinase (ADAM19) and ADAM with thrombospondin motifs (ADAMTS4) in ONH astrocytes. Hypothesis: IOP and remodeling of the ECM in the LC of the ONH are hallmarks of the pathogenesis of glaucoma. TGFβ2 is a profibrotic cytokine known to induce the synthesis and deposition of ECM. TGFβ2 increases ECM synthesis and deposition by ONH astrocytes within the LC, and RNA sequencing showed disintegrin and metalloproteinases (ADAMs) and ADAM with thrombospondin motifs (ADAMTS) were significantly dysregulated with TGFβ2 treatment compared to controls. Our lab has previously demonstrated that human ONH cells derived from glaucoma donors or treated with exogenous TGFβ2 increase profibrotic miRNAs and decrease anti-fibrotic miRNAs. MiR29c specifically, has been predicted to regulate members of the ADAM family proteins. Given that ADAMs and ADAMTS4 influence cell phenotype by modulating the ECM through cell adhesion, migration, proteolysis, and signaling pathways (19), we hypothesize that ONH astrocytes express ADAM19 and ADAMTS4 and that TGFβ2 and miR29c regulates ADAM19 and ADAMTS4 expression in ONH astrocytes. Significance: The existing treatments for glaucoma primarily focus on reducing IOP, which has proven effective in slowing the progression of the condition in many cases; however, it falls short of halting vision loss. To fully comprehend the intricacies of glaucoma pathology, investigating the expression of ADAM proteins in response to treatment with or without TGFβ2 in ONH astrocytes can provide insights that contribute to a better understanding of the disease and, potentially, the development of more holistic therapeutic approaches.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/32901
dc.language.isoen
dc.subjectastrocytes
dc.subjectoptic nerve head
dc.subjectADAM
dc.subject.meshAstrocytes
dc.subject.meshOptic Disk
dc.subject.meshGlaucoma
dc.titleADAM19 and ADAMTS4 expression in Human Optic Nerve Head Astrocytes
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentSchool of Biomedical Sciences
thesis.degree.disciplineMedical Sciences Research
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameMaster of Science

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