Food-derived bioactive compounds in ocular diseases: molecular mechanisms, clinical evidence, and translational challenges.
Age-related and chronic ocular diseases share common underlying mechanisms including oxidative stress, low-grade inflammation, mitochondrial dysfunction, and neurodegeneration. In parallel with advances in conventional therapies, interest in bioactive compounds derived from dietary sources (nutraceuticals) has increased due to their multiple molecular effects and potential to modulate the pathways leading to ocular disease. In this work, the current evidence for major classes of nutraceuticals, including carotenoids, polyphenols, organosulfur compounds, and other plant-derived metabolites was examined, with emphasis on their pharmacodynamic properties, mechanisms of action, and clinical relevance in ocular health. Mechanistic insights from in vitro and animal models were integrated with findings from clinical studies, highlighting molecular targets such as Nrf2-mediated antioxidant responses, NF-κB-driven inflammation, angiogenic signalling, and mitochondrial function. Carotenoids including lutein and zeaxanthin show the most consistent clinical evidence, particularly in increasing macular pigment optical density and reducing progression to advanced macular degeneration. In contrast, other carotenoids and most polyphenols including flavonoids, curcumin, and resveratrol demonstrate promising anti-inflammatory and anti-angiogenic effects primarily supported by preclinical data, with limited and heterogeneous clinical validation. Overall, current evidence suggests that nutraceuticals may have different effects and applicability in managing ocular diseases, although the majority of compounds discussed remain supported only by mechanistic and preclinical data, instead of clinical evidence. Future progress will require rigorously designed clinical studies, improved pharmacokinetic characterization, and precise stratification of patient populations to establish their therapeutic efficacy and relevance.