ADAM19 and ADAMTS4 expression in Human Optic Nerve Head Astrocytes

dc.creatorEaso, Tonyen_US
dc.creatorRangan, Rajiven_US
dc.creatorTovar-Vidales, Taraen_US
dc.description.abstractPurpose: Glaucoma is characterized by the degeneration and death of retinal ganglion cells and their axons causing irreversible blindness. Various risk factors contribute to glaucoma onset, including intraocular pressure (IOP), age, and family history. In glaucoma, the primary site of damage is the optic nerve head (ONH). ONH astrocytes, a major cell type in the LC, are believed to play a significant role in the pathological remodeling of extracellular matrix (ECM) during glaucoma. Glaucoma patients have increased levels of transforming growth factor beta 2 (TGFβ2) in their aqueous humor, trabecular meshwork and ONH. TGFβ2 is a profibrotic cytokine known to induce the synthesis and deposition of ECM. Previously, we performed RNA sequencing of ONH astrocytes in which disintegrin and metalloproteinases (ADAMs) and ADAM with thrombospondin motifs (ADAMTS) were significantly dysregulated with TGFβ2 treatment compared to controls. ADAMs and ADAMTS4 influence cell phenotype by affecting cell adhesion, migration, proteolysis, and signaling pathways. The purpose of the present study was to determine a) if ONH astrocytes express ADAM19 and ADAMTS4 in ONH astrocytes and b) determine if TGFβ2 regulates ADAM19 and ADAMTS4 expression in ONH astrocytes. Methods: Primary human ONH astrocyte cell strains (n=3) were treated with TGFβ2 (5ng/ml) or with a vehicle control for 48 hours. The effects of TGFβ2 on ADAM19 and ADAMTS4 were determined by qPCR and western blots using primary human ONH astrocyte cell cultures. Results: ADAM19 and ADAMTS4 were expressed in ONH astrocytes. Treatment with TGFβ2 significantly increased mRNA levels of ADAM19 and ADAMTS4. However, western blot analysis showed no significant change in ADAM19 protein expression compared to control, while ADAMTS4 was increased with TGFβ2 compared to control. Conclusions: TGFβ2 modulated the expression of ADAM19 and ADAMTS4 in ONH astrocytes. ADAM19 and ADAMTS4 may contribute to the pathogenic remodeling of the ONH in glaucoma. While further studies are needed, this research aims to shed light on the intricate mechanisms underlying glaucoma pathogenesis.en_US
dc.titleADAM19 and ADAMTS4 expression in Human Optic Nerve Head Astrocytesen_US