Myopia development: multifactorial interplay, molecular mechanisms and possible strategies

Area of Science:

• Ophthalmology and Molecular Biology: Investigating the complex molecular mechanisms underlying myopia progression.

Background:

• Myopia is a significant global visual impairment with multifactorial causes.
• Key pathways include neurotransmitter signaling (dopamine, GABA), hormonal influences (sex hormones, vitamin D), and intracellular cascades.

Purpose of the Study:

• To elucidate the intricate molecular pathways involved in myopia pathogenesis.
• To explore potential multi-target intervention strategies for myopia control.

Main Methods:

• Review of existing literature on myopia mechanisms.
• Analysis of signaling pathways like dopamine D2 receptor-cAMP, GABA, VDR, hypoxia-HIF-1α-MMP-2, TGF-β, and Wnt/β-catenin.
• Evaluation of emerging therapeutic strategies including low-dose atropine, outdoor light exposure, gene editing (CRISPR), and MMP-2 inhibitors.

Main Results:

• Dopamine and GABA signaling play crucial roles in regulating axial growth and refractive stability.
• Sex hormones and vitamin D exhibit complex, dose-dependent effects on scleral extracellular matrix (ECM) metabolism.
• The hypoxia-inducible factor 1-alpha (HIF-1α)-matrix metalloproteinase-2 (MMP-2) axis drives scleral ECM degradation.

Conclusions:

• Multi-target interventions, such as low-dose atropine with outdoor light, show promise for inhibiting axial elongation.
• Gene editing and targeted MMP-2 inhibitors are under preclinical investigation but face significant clinical translation challenges.
• Further research integrating molecular mechanisms and interdisciplinary approaches is essential for developing effective myopia prevention and control strategies.