Heavy metals and ocular toxicity: Breakthroughs in accumulation mechanisms, molecular pathways, and cutting-edge therapeutic strategies

Heavy metal pollution has emerged as a significant environmental health concern, particularly due to its capacity for selective bioaccumulation in ocular tissues. This comprehensive review systematically synthesizes current evidence regarding the accumulation patterns, molecular toxicity pathways, and therapeutic countermeasures against heavy metal-induced ocular damage. Experimental and clinical studies have demonstrated that heavy metals, including cadmium, lead, mercury, and cobalt, exhibit preferential accumulation in critical ocular structures such as the retinal pigment epithelium, lens, and aqueous humor. Epidemiological investigations reveal substantially elevated metal concentrations in patients diagnosed with age-related macular degeneration, cataracts, and glaucoma, suggesting a potential dose-response relationship. Two primary exposure routes have been characterized: direct transcorneal permeation through airborne particulate matter and systemic translocation across blood-ocular barriers facilitated by divalent metal transporter 1 and voltage-gated calcium channels. Following accumulation, these metals initiate complex pathological cascades involving oxidative stress through glutathione depletion, mitochondrial electron transport chain dysfunction, calcium signaling disruption in photoreceptors, and inflammatory activation. Current intervention strategies encompass physical protection measures, pharmacological approaches targeting oxidative stress pathways, probiotic modulation of the gut-retina axis, and advanced surgical techniques for late-stage pathologies. Critical knowledge gaps remain regarding trans-barrier transport kinetics and mixed metal toxicities. Future research should prioritize the application of artificial intelligence for toxicity prediction, CRISPR-based gene editing to enhance blood-retinal barrier integrity, and integrated multi-omics frameworks to establish tissue-specific exposure thresholds and develop precision ophthalmology approaches for ocular protection in increasingly contaminated environments.