From genes to vision: Insights into the role of PARP8 and hsa-miR-410-3p in myopia pathogenesis.

Abstract

This study investigated the genetic and functional association between PARP8 gene and high/extreme myopia (HM/EM) in a Han Chinese population. Genotyping of five SNPs (rs11954386, rs2404958, rs282544, rs32396, and rs27243) in PARP8 across 1768 participants revealed a significant association with HM/EM. Notably, rs27243 (situated in the 3'-UTR region of PARP8) exhibited a robust linkage. Experimental validations confirmed that the rs27243 A allele created a binding site for hsa-miR-410-3p, which led to the downregulation of PARP8 expression. Furthermore, diminished PARP8 and elevated hsa-miR-410-3p levels were detected in patients, along with reduced PARP8 expression in form-deprivation myopia mouse models, suggesting that PARP8 and hsa-miR-410-3p are potential risk factors or biomarkers for HM/EM. Collectively, these findings establish PARP8 as a novel susceptibility gene for HM/EM and reveal hsa-miR-410-3p-mediated post-transcriptional regulation of PARP8 as a pivotal mechanism in myopia pathogenesis.