Modulation of Mitochondrial Metabolic Parameters and Antioxidant Enzymes in Healthy and Glaucomatous Trabecular Meshwork Cells with Hybrid Small Molecule SA-2

Oxidative stress (OS)-induced mitochondrial damage is a risk factor for primary open-angle glaucoma (POAG). Mitochondria-targeted novel antioxidant therapies could unearth promising drug candidates the management of POAG. Previously, our dual-acting hybrid molecule SA-2 with nitric oxide-donating and activity reduced intraocular pressure improved aqueous humor outflow in rodent eyes. Here, we examined mechanistic role trabecular meshwork (TM) cells vitro measured intracellular enzymes during OS. Primary human TM isolated from normal (hNTM) or glaucomatous (hGTM) post-mortem donors transformed (GTM-3) were used assays. We effect on oxygen consumption rate (OCR) extracellular acidification (ECAR) using Seahorse Analyzer without oxidant, tert-butyl hydroperoxide (TBHP) treatment. Concentrations total enzymes, catalase (CAT), malondialdehyde (MDA), glutathione peroxidase (GPx) measured. observed significant protection both hNTM hGTM TBHP-induced cell death by SA-2. Antioxidant elevated SA-2-treated compared to TBHP-treated cells. In addition, demonstrated an increase metabolic parameters. Altogether, protected OS via increasing energy parameters enzymes.