Am J Pathol. 2025 Sep 12:S0002-9440(25)00342-6. doi: 10.1016/j.ajpath.2025.07.018. Online ahead of print.
ABSTRACT
Myopia progression and its associated complications, which can lead to vision impairment, primarily result from persistent abnormal elongation of the eye’s axial length. The previous metabonomic analysis of intraocular fluids suggested intraocular hormones may play a role in high myopia pathogenesis. In this study, significantly reduced concentrations of dehydroepiandrosterone (DHEA) were discovered in the vitreous humor (VH) of high myopia eyes. Additionally, DHEA levels in retina tissues of myopic guinea pigs were significantly decreased, further linking intraocular DHEA depletion to myopia-related tissue changes. Recent research has established scleral hypoxia as a fundamental mechanism underlying myopia development, with scleral fibroblasts serving as key functional cells in this process. Thus, this study investigated the effects of DHEA on human scleral fibroblasts (HSFs) under hypoxic conditions to generate novel insights for myopia prevention and treatment. The findings demonstrated that DHEA downregulates Hypoxia-inducible factor 1α (HIF-1α) expression and reduces collagen loss under hypoxic conditions. Additionally, DHEA reversed the decreased cell proliferation observed in HSFs in vitro. These effects appear to be mediated through changes in mitochondrial dynamics and regulation of BNIP3L-mediated mitophagy induced by DHEA under hypoxia. The results suggest DHEA represents a promising novel therapeutic strategy for preventing myopia development.
PMID:40946797 | DOI:10.1016/j.ajpath.2025.07.018