Nicotinamide Riboside Mitigates Oxidative Damage and Fibrosis in Trabecular Meshwork Cells: Preclinical Findings

Synopsis

Glaucoma is a leading cause of irreversible blindness, often caused by dysfunction and scarring in the trabecular meshwork (TM)—the eye tissue that regulates fluid drainage and intraocular pressure. This study explored how nicotinamide riboside (NR), a vitamin B3–derived NAD+ precursor, protects human trabecular meshwork (HTM) cells from oxidative stress and fibrosis, two major contributors to glaucoma. When HTM cells were exposed to hydrogen peroxide (H₂O₂) to induce oxidative injury and TGF-β2 to trigger fibrosis, NR pretreatment improved cell survival, mitochondrial health, and proliferation. NR also reduced reactive oxygen species (ROS) levels, prevented cell death, and preserved mitochondrial membrane potential. Importantly, NR inhibited cell migration and fibronectin buildup, key features of fibrosis. Mechanistically, NR activated the JAK2/STAT3 pathway, which supports cell survival, and suppressed the MAPK pathway, which promotes inflammation and fibrosis. These results suggest that NR protects TM cells by reducing oxidative and fibrotic stress, highlighting its potential as a novel therapeutic approach for glaucoma.

Journal

Translational Vision Science & Technology