Mechanisms Underlying Myopia Progression from Visual Signaling to Metabolic Remodeling in Retina

Myopia has emerged as a major global health concern due to its rising prevalence and the associated risk of irreversible visual impairment. Although scleral and choroidal changes have traditionally received emphasis, recent studies highlight the retina as a key contributor to the onset and progression of myopia. This review incorporates recent advances across three interrelated domains: visual pathway modulation, functional impairment, and metabolic remodeling. Abnormal ON pathway signaling-particularly under mesopic lighting-disrupts emmetropization feedback and promotes ocular elongation. As myopia progresses, retinal dysfunction unfolds in a temporal cascade, beginning in the inner retina and eventually leading to widespread structural and functional degeneration. Concurrently, the retina exhibits stage-dependent metabolic shifts, progressing from early mitochondrial and lipid metabolism changes to mid-phase destabilization of membrane integrity, and culminating in late-stage oxidative stress, inflammation, and metabolic remodeling. Collectively, these findings redefine myopia as a progressive retinal disorder and underscore the potential of retina-targeted interventions to preserve homeostasis and mitigate long-term degeneration.