Chrononutrition as a modulator of retinal metabolic resilience: A translational framework linking circadian biology to ocular disease.

Chrononutrition-the alignment of feeding-fasting cycles with endogenous circadian rhythms-has emerged as a key determinant of systemic metabolic homeostasis. However, its relevance in ocular biology and retinal disease remains insufficiently defined within a translational framework. The retina, characterized by high energetic demand, intrinsic circadian oscillators, and tight coupling between mitochondrial function and redox balance, represents a uniquely vulnerable target to chrono-metabolic disruption. Here, we propose a mechanistically integrated model in which feeding timing acts as a systemic regulator of retinal metabolic resilience. We synthesize evidence demonstrating that circadian misalignment and irregular nutrient intake disrupt retinal bioenergetics, impair insulin signaling, and promote mitochondrial dysfunction and oxidative stress-hallmarks of major retinal diseases including diabetic retinopathy, age-related macular degeneration, and glaucomatous neurodegeneration. Particular emphasis is placed on nutrient-sensitive pathways, including peroxisome proliferator-activated receptors (PPARs), the AMPK/SIRT1 axis, and melatonin-mediated chronoregulation, as key interfaces linking metabolic cues with retinal circadian control. Importantly, we advance the concept that chrononutrition extends beyond dietary composition to function as a temporal modulator of disease-relevant pathways. Based on convergent experimental evidence, we outline a translational framework in which rhythm-aligned feeding patterns and time-dependent nutritional interventions may enhance mitochondrial efficiency, stabilize redox homeostasis, and improve retinal stress adaptation. Although direct clinical evidence remains limited, this paradigm provides a biologically grounded basis for the development of chrono-nutritional strategies as adjunctive approaches in retinal disease prevention and management.