Heavy Metal-Induced Retinal Injury in Zebrafish (Danio rerio): Histopathological Alterations, Molecular Mechanisms...

Heavy metal contamination is a significant environmental risk factor for ocular dysfunction and retinal degeneration in both aquatic organisms and humans. Zebrafish (Danio rerio) have become an important vertebrate model for retinal toxicology research due to their conserved retinal architecture, cone-rich visual system, optical transparency during development, and remarkable capacity for retinal regeneration. This narrative review synthesizes current evidence on the effects of heavy metals on the development, structure, function, and regenerative responses of the zebrafish visual system, with particular focus on retinal alterations, molecular mechanisms, and visual impairment. Studies indicate that exposure to cadmium, lead, arsenic, chromium, copper, mercury, and metal mixtures results in retinal disorganization, photoreceptor degeneration, vacuolization, retinal pigment epithelium damage, impaired retinogenesis, and alterations in visually mediated behaviors. Mechanistic investigations reveal that heavy metal-induced retinal toxicity involves oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, apoptosis, neuroinflammation, DNA damage, and dysregulation of genes critical for retinal development and photoreceptor maintenance. Functional assays, such as the optomotor response and optokinetic reflex, provide sensitive endpoints for detecting visual dysfunction that may precede overt structural degeneration. Furthermore, the unique regenerative capacity of the zebrafish retina, primarily mediated by Müller glia reprogramming, provides valuable opportunities to study endogenous retinal repair following toxic injury. Overall, current evidence establishes zebrafish as a versatile and translationally relevant model for investigating heavy metal-induced retinal injury, visual dysfunction, and regenerative responses. Future research that incorporates environmentally relevant exposure paradigms, mixture toxicology, multi-omics approaches, and regenerative signaling pathways is likely to enhance understanding of metal-associated retinal disease and support the development of novel therapeutic strategies for retinal degeneration and vision loss.