Effect of Cyclosporine A on Oxidative Stress in Trabecular Meshwork Cells and Trabecular Outflow

Purpose: This study investigated the effects of cyclosporine A (CSA) on oxidative stress and trabecular outflow in human trabecular meshwork cells (HTMCs). Additionally, its impact on intraocular pressure (IOP) was evaluated.Methods: HTMCs were exposed to 1.0 μM and 10 μM of CSA for 24 hours. Cell viability and nitric oxide (NO) production were assessed using the MTT assay and Griess assay, respectively. Reactive oxygen species (ROS) generation and superoxide production were measured using the DCFH-DA assay and a modified cytochrome C assay. Endothelial nitric oxide synthase (eNOS) protein expression was analyzed through Western blotting, while HTMC monolayer permeability was evaluated using trans-epithelial endothelial resistance (TEER) measurements. IOP changes were assessed in 18 glaucoma patients who had used topical CSA for dry eye disease over 6 months.Results: Treatment with 10 μM of CSA reduced cell viability and NO production. CSA also decreased eNOS protein activity and ROS generation without affecting superoxide production. Additionally, 10 μM of CSA increased TEER, indicating decreased permeability of the HTMC monolayer. However, IOP changes in patients using topical CSA were not statistically significant (<i>p</i> = 0.365) over the 6-month period.Conclusions: CSA reduced NO production and eNOS protein activity while increasing oxidative stress in HTMCs. It also decreased HTMC monolayer permeability. However, topical CSA did not significantly alter IOP in glaucoma patients.