Advocating gut-retina connection and microbiota mediated pathways in management of age-related macular degeneration: preclinical to clinical perspective

Age-related macular degeneration (ARMD) is the primary manifestation of permanent vision loss internationally. Different factors that contribute to ARMD involve ageing, genetic predisposition, oxidative stress, immunological imbalances, aberrations in the breakdown of lipids, and persistent inflammation. Gut microbiota has emerged as the significant cause of ARMD by disrupting systemic immune and inflammatory responses and metabolic homeostasis. Age-related changes in gut microbiota (dysbiosis) cause lowered microbial diversity, enhanced gut permeability, and pro-inflammatory species, leading to macular damage. The healthy gut microbiota containing Lactobacillus casei, Lactobacillus plantarum , Lactobacillus rhamnosus, Bifidobacterium bifidum, Bifidobacterium breve , Bifidobacterium longum, and Faecalibacterium prausnitzii, are responsible for maintaining gut homeostasis, protecting the retina, and preventing ARMD progression. In contrast, the elevated population of pathogenic species such as Escherichia coli, Prevotella, Desulfovibrio, Enterococcus faecalis , and Streptococcus salivarius in gut dysbiosis is involved in ARMD progression. This review explores gut microbiota and their dynamics in ageing. The age-dependent gut microbiota variations and potential biological implications for the progression of ARMD are discussed. The review also discusses observations from experimental animals and explores potential microbiome-centered treatment avenues, covering probiotics, synbiotics, dietary remedies, metabolite-based treatment, and fecal microbiota transplantation for managing ARMD. Furthermore, various challenges in the management of gut microbiota-driven ARMD are also briefed with future directions. Thus, a gut microbiota-focused paradigm can offer novel choices for ARMD prevention and treatment.