NMN shields the eye's lens from fibrotic cataract by calming ferroptosis in preclinical models

Cataract is the world's leading cause of blindness, and fibrotic forms, where lens cells transform and lay down scar-like tissue, make up a meaningful share of cases. Surgery is effective, but fibrosis can recur or cloud vision afterward, and no drug prevents it. Oxidative stress and ferroptosis, an iron-dependent cell death driven by lipid peroxidation, have been implicated in the process.

Researchers tested whether NMN, a precursor of the cellular coenzyme NAD+, could interrupt this cycle. They combined three approaches: analysis of clinical samples from patients with fibrotic cataract (ASC) and controls, experiments in human lens epithelial cells (SRA01/04) treated with TGF-β2 to induce fibrosis, and a mouse model of ASC treated with NMN. The cell work included an Nrf2 inhibitor, ML385, to test mechanism.

Patient samples showed lower GPX4, FTH1 and glutathione, with higher ACSL4, malondialdehyde and Fe2+, a pattern consistent with ferroptosis. In cells, NMN blocked TGF-β2-induced increases in lipid ROS, MDA and iron, and prevented glutathione loss. It reversed the fall in E-cadherin and suppressed collagen I, collagen IV and α-SMA, indicating reduced EMT and fibrosis. It also affected TNF-α and IL-6. ML240-style rescue was lost when Nrf2 was inhibited, pointing to Nrf2 dependence. In mice, NMN restored lens architecture, reduced fibrosis, and normalized iron, MDA and glutathione through Nrf2/FPN1 activation.

The work links NAD+ biology to ferroptosis control in the lens and nominates the Nrf2/FPN1 axis as a therapeutic target, possibly for preventing posterior capsule opacification or fibrotic cataract.

Caveats are substantial. This is based on the abstract only, so sample sizes, dosing, route of delivery and statistics are unknown. Cell lines and a mouse model may not reflect human disease, and no human NMN treatment data are presented.