Targeting the Gut-Retina Axis in Age-Related Retinopathies: Microbiome-Immunometabolic Pathways and Gerotherapeutic Perspectives.

Age-related retinopathies refer to a spectrum of retinal disorders primarily associated with aging, characterized by chronic oxidative stress, sustained inflammatory responses, and progressive visual impairment. Aging significantly influences the gut-retina axis by altering the gut microbiota and increasing intestinal permeability, thereby contributing to retinal pathology. The gut microbiota undergoes continuous coevolution with the host, and its composition and function are altered with advancing age. A persistent imbalance within the gut microbial community, known as dysbiosis, can increase intestinal permeability. This thereby allows microbes and their metabolites to more easily cross the epithelial barrier. These microbiota and metabolites can migrate to the retina via the gut-retina axis, potentially eliciting inflammatory responses and immune dysregulation. Such mechanisms have been involved in the occurrence and progression of diverse age-related retinopathies. This review delves into these bidirectional interactions within the gut-retina axis and their intricate implications for the pathogenesis of age-related retinopathies. A central focus is the pivotal role of gut microbiota and their metabolites in inducing retinal inflammation and immunological dysregulation. We endeavor to elucidate the synergistic mechanisms through which the neural, immune, and endocrine systems influence the pathology of age-related retinopathies. Furthermore, recent therapeutic trials targeting gut microbiota for the management of retinopathy are also discussed. These findings would provide novel insights and robust theoretical foundation for future advancement of innovative therapeutic strategies.