MM-102

Antioxidants Protect Trabecular Meshwork Cells From Hydrogen Peroxide-Induced Cell Death

Purpose: To look at the protective results of antioxidants in cultured trabecular meshwork (TM) cells uncovered to oxidative stress.

Methods: Primary porcine TM cells were pretreated with 50 µM resveratrol, .2 mM urate, 1 mM ascorbate, 1 mM reduced glutathione (rGSH), or 1 mM ?-coumarate adopted by contact with peroxide (.5-4 mM). Cell metabolic process was resolute by mitochondrial enzyme activity and cell viability by uptake from the vital dye calcein, a fluorescent calcium binding dye. Reactive oxygen species (ROS), which might reflex oxidative damage, were based on 2’7′-dichlorofluorescein diacetate.

Results: Trabecular meshwork cell metabolic process was reduced to MM-102 72 ± 5% of control levels with 1 mM peroxide (H2O2) treatment. TM cells that co-incubated with ascorbate (85% ± 5%), ?-coumarate (98 ± 11%) or rGSH (103 ± 17%) had considerably elevated metabolic process when compared with 1 mM H2O2 treatment. Resveratrol considerably elevated TM cell metabolic process at both 2 mM (102 ± 14% live) and 4 mM H2O2 (27 ± 12% live), with H2O2-treated cultures that contains mostly metabolically inactive cells (3% at 2 mM 2% at 4 mM). Similar outcome was acquired in cell viability assays. Ascorbate and resveratrol, although not ?-coumarate or rGSH, decreased ROS levels in TM cells uncovered to some sublethal dose of H2O2 (.5 mM). Urate didn’t have protective effect against H2O2 damage most of the assays.

Conclusions: Elevated oxidative damage was shown within the TM of patients with primary open position glaucoma. The antioxidants (resveratrol, ascorbate, ?-coumarate) and also the antioxidant enzyme cofactor (rGSH) protected TM cells from H2O2-caused damage.

Translational relevance: Future experiments are necessary to see whether inclusion of antioxidants may maintain TM cell viability in vivo. Antioxidants might be applied either topically or along with extended-release vehicles for MM-102 intraocular injection to lessen toxin formation resulting in enhanced therapeutic outcomes. Ultimately, studies using animal models could see whether use of antioxidants can improve progression in illnesses for example glaucoma and macular degeneration.