Hepato-ocular crosstalk: Bile acids bridging pathogenesis and therapy

Bile acids, the major metabolites of cholesterol, function as pleiotropic signaling molecules beyond their classical role in lipid digestion. Increasing evidence indicates that dysregulated bile acid metabolism represents a shared molecular basis linking hepatic dysfunction with ocular pathology. Aberrations in bile acid synthesis, transport, and signaling lead to bile acid imbalance, which drives ocular injury through direct cytotoxicity, disruption of retinal and lens homeostasis mediated by FXR and TGR5 signaling, and immune activation along the gut-liver-eye axis. These mechanisms are implicated across a spectrum of conditions, ranging from inborn metabolic disorders to acquired cholestatic diseases. This review further highlights the translational potential of targeting bile acid homeostasis. We summarize emerging therapeutic strategies, including bile acid-based interventions, targeted drug delivery, and microbiome modulation, that aim to restore systemic bile acid balance. Collectively, we propose reconstruction of systemic bile acid homeostasis as a unifying therapeutic framework for hepato-ocular comorbidities.