Intermittent fasting attenuates glial hyperactivation and photoreceptor degeneration in a NaIO-induced mouse model of age-related macular degeneration.

Abstract

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss, with limited treatments available. Recent studies suggest intermittent fasting (IF) may offer neuroprotective benefits for aging and age-related disorders, but its efficacy in AMD has not yet been established. Here, using a sodium iodate (NaIO)-induced AMD model in male mice, we find that pretreatment with an IF diet regimen mitigates NaIO-induced cellular damage and loss of both retinal pigment epithelium (RPE) and photoreceptors. Visual function tests indicate that IF preserves vision in NaIO-treated mice. Transcriptome analyses show IF counteracts NaIO-induced transcriptional dysregulation, affecting genes related to reactive oxygen species (ROS), inflammation, and photoreceptor structure. Further experimental results confirm that IF effectively reduces ROS levels and inhibits the activation of microglia and Muller cells in the retina. Collectively, these findings indicate that IF reduces ROS production and inflammation in NaIO-induced retinal damage, providing a potential therapeutic strategy for oxidative stress-induced retinal degenerative diseases, including AMD.