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Abstract #112865 Published in IGR 24-3
Effects of Brimonidine, Omidenepag Isopropyl, and Ripasudil Ophthalmic Solutions to Protect against HO-Induced Oxidative Stress in Human Trabecular Meshwork Cells
Liu M; Honjo M; Yamagishi R; Aihara MCurrent Eye Research 2023; 48: 1014-1025
PURPOSE: We investigated whether hydrogen peroxide (HO)-induced oxidative stress causes human trabecular meshwork (HTM) cell dysfunction observed in open angle glaucoma (OAG) , and the effects of topical glaucoma medications on oxidative stress in HTM cells. METHODS: We used commercially available ophthalmic solutions of brimonidine, omidenepag isopropyl, and ripasudil in the study. HTM cells were exposed to HO for 1 h, with or without glaucoma medications. We assessed cell viability and senescence WST-1 and senescence-associated-β-galactosidase (SA-β-Gal) activity assays. After exposure to HO and glaucoma medications, we evaluated changes in markers of fibrosis and stress by using real-time quantitative polymerase chain reaction (qPCR) to measure the mRNA levels of collagen type I alpha 1 chain (COL1A1), fibronectin, alpha-smooth muscle actin (α-SMA), matrix metalloproteinase-2 (MMP-2), endoplasmic reticulum stress markers of C/EBP homologous protein (CHOP), 78-kDa glucose-regulated protein (GRP78), and splicing X-box binding protein-1 (sXBP-1). RESULTS: HTM cell viability decreased and SA-β-Gal activity increased significantly after exposure to HO. Treatment with three ophthalmic solutions attenuated these changes. Real-time qPCR revealed that HO upregulated the mRNA levels of COL1A1, fibronectin, α-SMA, CHOP, GRP78, and sXBP-1, whereas it downregulated MMP-2 mRNA expression significantly. Brimonidine suppressed the upregulation of stress markers CHOP and GRP78. Additionally, omidenepag isopropyl and ripasudil decreased the upregulation of COL1A1 and sXBP-1. Furthermore, ripasudil significantly suppressed fibrotic markers fibronectin and α-SMA, compared with the other two medications. CONCLUSION: Array
Department of Ophthalmology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
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