Visual cycle and LC3-associated phagocytosis in retina: regulatory mechanisms and therapeutic potential.

Abstract

The visual cycle plays a pivotal dual role in retina, while it's essential for maintaining vision through continuous regeneration of the light-sensitive 11-cis-retinal chromophore. Its dysregulation contributes significantly to retinal degenerative disorders including age-related macular degeneration (AMD) and Stargardt disease. Recent advances have elucidated multiple therapeutic targets in visual cycle, ranging from inhibition of enzymatic activity of RPE65 and lecithin retinol acyltransferase (LRAT) to modulation of retinoid transport proteins and enhancement of protective LC3-associated phagocytosis. Pharmacological interventions of the visual cycle demonstrate promising results in reducing toxic retinoid accumulation, though clinical application faces challenges including nyctalopia, delayed dark adaptation, and dyschromatopsia. Future research directions emphasize the need for targeted visual cycle modulators that can selectively disrupt pathological processes without compromising essential visual function. This review summarizes the visual cycle and LC3-associated phagocytosis associated with various retinal diseases, highlights recent advances in pharmacological modulation of visual cycle, and aims to provide new insights into therapeutic strategies for retinal degenerative disorders.