The stress-myopia pathway: A pivotal hub in myopia pathogenesis

Myopia presents a significant global public health challenge, with high myopia markedly increasing the risk of irreversible visual impairment. While myopia involves complex etiological and pathophysiological mechanisms, no effective treatments currently exist for the core pathological changes of axial elongation. This paper proposes the "stress-myopia pathway" working hypothesis for the first time, which posits that various risk factors (such as genetic, environmental, and near-work with academic pressure, screen exposure, etc.) function as stressors that drive myopia progression through a shared pathway: a chronic stress response. The resulting pathological changes then exacerbate the stress response, creating a vicious cycle. Chronic stress response activates the hypothalamo-pituitary-adrenal (HPA) axis and the sympatho-adrenal medullary (SAM) system, releasing catecholamine (CA) and glucocorticoid (GC), which lead to neuroendocrine disorders, autonomic nervous system (ANS) dysregulation, oxidative stress injury, endoplasmic reticulum (ER) stress, inflammatory cascades, metabolic abnormalities, and "gut-brain-eye axis" dysfunction. These alterations are seriously associated with scleral remodeling, choroidal thinning, abnormal retinal signals, vitreous liquefaction and refractive changes. Given this understanding, we discuss the potential of multimodal strategies for managing stressors and chronic stress responses, including but not limited to non-invasive vagus nerve stimulation (nVNS), behavioral therapy, antioxidants, and gut microbiota therapy. These approaches may hold promise for preventing and controlling myopia, a crucial step in addressing the global myopia epidemic.