Implication of gut microbiome in age-related macular degeneration

age-related macular degenerationchoroidal neovascularizationcomplement factor Hdiet and microbiotagerm-free mice

Implication of gut microbiome in age-related macular degeneration

Why this matters for your gut health

AMD is a leading global cause of blindness, affecting roughly 196 million people worldwide with prevalence projected to reach 288 million by 2040. Wet (neovascular) AMD, though less common than dry AMD, accounts for 90% of AMD-related vision loss. Understanding the emerging “gut-retina axis” — how gut microbiome composition influences retinal inflammation and choroidal neovascularization (CNV) — opens new avenues for therapeutic strategies beyond current treatments, especially since disease mechanisms remain incompletely understood.

Summary

This perspective reviews preclinical and clinical evidence linking gut microbiome dysbiosis to AMD pathogenesis. Using germ-free (GF) and gnotobiotic mouse models, the authors’ lab and others have shown that absence of gut microbiota alters chorioretinal transcriptomes, affects angiogenesis/inflammation pathways, and modulates CNV lesion severity. Diet (high-fat, high-glycemia) and aging both influence gut microbial composition, which in turn affects retinal inflammation via increased intestinal permeability, pathogen-associated molecular pattern circulation, and downstream immune activation. Clinical metagenomic studies in AMD patients further support distinct microbial signatures associated with disease state, and genetic risk factors (CFH, ARMS2) appear to interact with gut dysbiosis to influence AMD development.

Key findings

GF mice show altered chorioretinal gene expression (660 DEGs vs. SPF mice), including changes in CXCR3, TIE1, TNF, and CFH — genes tied to angiogenesis/inflammation.
GF mice develop smaller CNV lesions and reduced microglial infiltration after laser-induced CNV compared to conventional (SPF) mice.
High-fat diet (HFD) increases CNV and gut dysbiosis (Firmicutes/Clostridia expansion), raises intestinal permeability and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-17A, IFN-γ); fecal transplant from normal-diet mice suppressed HFD-driven CNV.
High-glycemia diets induce AMD-like phenotypes (subretinal deposits, RPE atrophy, lipofuscin accumulation) linked to Clostridia enrichment; low-glycemia diets are protective and enrich Bacteroidales.
Fecal microbiota transfer from aged donor mice accelerates retinal inflammation in young mice; young donor microbiota reverses aging-related retinal damage in old mice.
Human AMD patients show distinct gut microbial signatures (e.g., enriched Prevotella, Holdemanella, Desulfovibrio, Negativicutes) and genetic risk alleles (CFH, ARMS2) correlate with reduced gut microbial diversity.