Selenide-modified hyaluronic acid hydrogel promotes scleral remodeling during the recovery phase of form-deprivation myopia by inhibiting HIF-1α-mediated inflammation.

This study investigates the molecular mechanisms by which selenide-modified hyaluronic acid hydrogel (Se-HA gel) promotes scleral remodeling during the recovery phase of form-deprivation myopia (FDM). The Se-HA gel was synthesized and characterized, exhibiting an average hydrodynamic diameter of 191.72 nm, a polydispersity index (PDI) of 0.19, and a zeta potential of -7.96 mV, indicating a monodisperse state in PBS. Both in vitro experiments and the FDM mouse model confirmed its therapeutic efficacy. At a concentration of 250 μg/mL, Se-HA gel significantly promoted fibroblast proliferation, inhibited apoptosis, and prevented transdifferentiation. A 200 mg/kg subtenon injection improved key ocular biometric parameters in FDM mice. Single-cell and transcriptomic sequencing analyses revealed that Se-HA gel facilitated scleral remodeling by downregulating Hypoxia-Inducible Factor 1 Alpha (HIF-1α) expression and regulating inflammation-related gene expression. Notably, HIF-1α overexpression reversed the beneficial effects of Se-HA gel, reinforcing its pivotal role in mediating these therapeutic outcomes. This study introduces a novel biomaterial-based strategy and identifies new molecular targets for myopia treatment. Furthermore, it addresses a critical gap in understanding how Se-HA gel promotes scleral remodeling through HIF-1α-mediated signaling pathways, with important scientific and translational potential in the field of myopia management.