Of the three chemicals, nitrate and thiocyanate exposure showed significant positive associations with AMD risk. Individuals in the highest quartile of urinary nitrate had a 94% higher odds of AMD, while those in the highest quartile of thiocyanate showed a 70% higher odds compared with those in the lowest quartile. Perchlorate levels, by contrast, were not significantly associated with AMD risk.
The team observed a U-shaped relationship between both nitrate and thiocyanate levels and AMD risk, suggesting that both low and high exposures might influence retinal health differently. In weighted quantile sum analysis — which considers the combined effects of chemical mixtures — a positive overall association was found between mixed exposure and AMD.
The authors propose several potential pathways for these effects. Nitrate, commonly found in leafy vegetables, cured meats, and contaminated water, is metabolized into nitric oxide (NO) — a molecule that can disrupt vascular and oxidative homeostasis in the retina. Excessive NO may lead to the formation of reactive nitrogen species such as peroxynitrite, contributing to retinal pigment epithelium (RPE) damage and photoreceptor apoptosis.
Thiocyanate, meanwhile, is a byproduct of cigarette smoke and certain industrial processes, as well as being found in cruciferous vegetables. In the retina, it may interact with myeloperoxidase (MPO) to generate oxidative stress within RPE lysosomes — mechanisms thought to underlie early AMD pathology.
Interestingly, perchlorate, another inhibitor of the sodium–iodide symporter, showed no significant correlation, possibly due to lower exposure levels or different biological pathways.
Although the findings do not establish causation, they add to mounting evidence that environmental exposures may influence retinal disease. The results highlight the importance of considering not just genetic and metabolic factors, but also toxicological influences on AMD development.
"Although the OR for the highest quartiles indicate moderate association," the study authors state, "such effect sizes may still be meaningful at the population level given the high prevalence of AMD and widespread exposure to these chemicals."
In order to confirm their findings, the authors are now calling for longitudinal and mechanistic studies to explore how reducing chemical exposure might complement existing preventive strategies in AMD care.
