Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in ageing populations, with oxidative stress recognised as a key pathogenic driver. The dietary antioxidant and cytoprotectant, L-ergothioneine (ET), is avidly accumulated in many tissues, especially the eye. However its relationship to AMD is unclear. Here, we examined ET’s distribution in human ocular tissues and measured serum and intraocular ET levels in patients with neovascular AMD. Compared with ocularly-normal age-matched individuals, AMD patients exhibited significantly lower serum ET; elevated levels of ET metabolites, hercynine and ETSO₃, which may be generated by oxidative stress; and elevated levels of serum allantoin, a biomarker of oxidative damage to urate in humans. Levels of ET in aqueous humour in AMD patients were marginally lower than cataractous patients, who are already known to have significantly lower ET levels than healthy eyes. High ET levels were seen in human ocular tissues, concentrating in regions vulnerable to oxidative damage, including the lens, retina, retinal pigment epithelium, and choroid, supporting a physiological protective role of ET in the eye. These findings identify a strong association between low ET levels and AMD, warranting further studies to determine whether ET supplementation can modify AMD risk or progression.
Cheah et al. (2026) studied this question.