Beyond direct toxicity: Cross-system regulation and the gut-retina axis in pollutant-induced visual dysfunction in...

The integrity of the fish visual system is a critical indicator of aquatic environmental health. However, the etiology of pollutant-induced visual impairment remains fragmented, and the impairment is rarely localized. To map the evolving landscape of this field, we first conducted a bibliometric analysis, which reveals a paradigm shift from initial phenomenological observations to complex mechanistic exploration. Informed by the key trends and knowledge gaps identified in this analysis, we then critically integrate the core pathological mechanisms of visual dysfunction: direct ocular toxicity and indirect cascading effects driven by cross-system interactions. For precise environmental monitoring, we synthesize diagnostic biomarkers specifically linked to these distinct toxicological mechanisms, providing a strategic framework for endpoint selection. Within this complex interaction landscape, we identify the gut-retina axis as a primary regulatory target in mediating visual toxicity. We provide a detailed examination of how pollutant-induced gut dysbiosis triggers systemic inflammation and alters metabolic signaling. By integrating these multidimensional findings, we propose a conceptual Adverse Outcome Pathway (AOP) framework. Distinct from traditional ocular-centric AOPs that focus on direct tissue damage, this AOP integrates cross-system signaling in the chain from gut dysbiosis to retinal neurotoxicity. This review provides a theoretical basis for understanding pollutant-induced visual dysfunction and offers an AOP-informed conceptual perspective for hypothesis generation and future ecotoxicological risk assessment in aquaculture ecosystems.