miR-29a regulates scleral remodelling via TLR7/8-dependent inflammatory signalling in myopia

Abstract

Myopia, especially high myopia, is a global health concern with a rising prevalence, yet its underlying mechanisms remain incompletely understood. MicroRNAs (miRNAs) have been implicated in the pathogenesis of myopia, potentially playing a critical role in its development. This study aimed to investigate the mechanism by which miR-29a mediates scleral remodelling through the activation of Toll-like receptors (TLRs). By using a form-deprivation myopia (FDM) guinea pig model, we combined fluorescence in situ hybridization (FISH) and qPCR to demonstrate that the expression of miR-29a and inflammatory cytokines (TNF-α and IL-6) was significantly upregulated in the sclera of myopic eyes, whereas TLR7/8 expression remained unchanged. In human scleral fibroblasts (HSFs), FISH and RNA immunoprecipitation (RIP) assays revealed that miR-29a directly interacts with TLR7 and TLR8, forming ligand‒receptor complexes. This interaction activated downstream inflammatory signalling, leading to upregulated expression of proinflammatory cytokines (TNF-α and IL-6), downregulated expression of anti-inflammatory IL-10, and suppression of COL1A1 expression. Inhibition of TLR7/8 signalling reversed these effects, restoring COL1A1 levels and attenuating inflammatory responses. Our findings reveal a novel mechanism by which miR-29a promotes scleral remodelling through TLR7/8-mediated inflammatory signalling, providing new insights into the pathogenesis of myopia and potential therapeutic targets for its prevention and treatment.