Myopia development: multifactorial interplay, molecular mechanisms and possible strategies

作者：Lihong Huang, Dazheng Zhang, Jing Zhou · 发表于：Frontiers in Medicine · 年份：2025 · DOI：10.3389/fmed.2025.1638184 · 被引用次数：11 · 研究领域：Ophthalmology and Visual Impairment Studies、Corneal surgery and disorders、Ocular Surface and Contact Lens

Myopia is a global visual impairment, and its pathological mechanism involves the complex multifactorial interplay of neurotransmitters, hormones and intracellular signaling pathways. Dopamine inhibits axial growth by activating D2 receptor-CAMP pathway, while GABA energy signals maintain refractive stability by regulating retinal excitation-inhibition balance. Sex hormones and vitamin D play a dual role by regulating scleral ECM metabolism, the former enhances corneal strength and may promote axial elongation during puberty, while the latter exhibits dose-dependent biphasic effects on collagen synthesis via VDR signaling. In the core signaling pathway, the hypoxia-HIF-1α-MMP-2 axis drives sclera ECM degradation, while TGF-β and Wnt/β-catenin pathways synergically regulate fibroblast proliferation and migration. In response to these mechanisms, multi-target intervention strategies show potential: low-dose atropine combined with outdoor light can synergically inhibit axial growth. However, while emerging technologies like gene editing (e.g., CRISPR targeting HIF-1α) and targeted MMP-2 inhibitors are entering preclinical validation, their clinical translation faces substantial hurdles. For CRISPR-based approaches, critical challenges include mitigating off-target editing risks and developing safe, efficient in vivo delivery systems to the relevant ocular tissues. Future studies need to integrate molecular mechanisms and interdisciplinary approaches to rigorously evaluate effica...