Ozone exposure and increased risk of age-related macular degeneration: Evidence from nationwide cohort and toxicological studies

Evidence regarding the impact of ozone on age-related macular degeneration (AMD) remains limited. We conducted a nationwide cohort analysis of 27,923 participants in China, along with a random control animal toxicological study, to elucidate the temporal relationship between ozone exposure and AMD as well as the underlying biological explanation. In the population study, 5,149 participants were diagnosed with incident AMD during a 348,701 person-month follow-up. The participants were divided into low-, medium-, and high-exposure groups. Fully adjusted Cox regression models showed that the risk of AMD increased by 28% for the medium- and 101% for the high-exposure groups relative to the low-exposure group (<i>p</i> for trend < 0.001). The exposure-response curves exhibited a J-shaped trend. Sensitivity analyses confirmed these results, revealing stronger associations among participants older than 65 years old and those living in rural or northern China. In the toxicological study, the mice were randomized to inhale ozone or filtered air, and those exposed to ozone had photoreceptor damage and vision impairment, which are hallmarks of AMD. We further clarified that ozone exposure contributes to AMD by activating systemic inflammation and detailing how external air-pollutant-induced inflammation factors reach the retina, which is the innermost layer of the eye, and cause retinal disease. Our comprehensive studies provide key evidence on the temporal relationship between ozone exposure and increased AMD risk, suggesting the visual health benefits of collaboratively enforcing necessary ozone pollution control policies, especially in regions with high ozone concentrations, within the context of a globally aging population.