Mingshi Formula, a traditional Chinese medicine, was tested in a guinea pig form-deprivation myopia model and dose-dependently reduced myopic shift, axial elongation, and choroidal thinning while improving scleral structure. Mechanistically, it inhibited mTOR phosphorylation and HIF‑1α signaling, lowered glycolytic enzymes (LDHA, PKM2), and normalized ECM markers (MMP2, Collagen I, α‑SMA), thereby alleviating scleral hypoxic metabolic remodeling. Objective refraction with a Striatech Photorefractor and SD‑OCT–based choroidal measurements were essential to quantify these treatment effects.
Focusing on the mTOR-HIF-1α signaling pathway, this study investigated the mechanism through which the traditional Chinese medicine compound Mingshi Formula delays the progression of form-deprivation myopia (FDM) in guinea pigs. The guinea pigs were divided into the normal control group (NC), FDM group, Mingshi Formula low-dose group (FDM + Low), medium-dose group (FDM + Medium), high-dose group (FDM + High), and MTOR inhibitor group (FDM + RapaLink-1). The guinea pig model of FDM was established by applying 3D-printed hoods modified by a latex balloon with 60% light transmission for 4 weeks. Refractive error changes were monitored using a refractometer. Axial length was quantitatively analyzed using A-scan ultrasound, choroidal thickness was measured with SD-OCT, and structural changes of the choroid and sclera were observed after hematoxylin-eosin (HE) staining. At the molecular level, the expression levels of the mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), HIF-1α, LDHA, PKM2, MMP2, Collagen I, and α-SMA in the sclera were measured by RT-qPCR and Western blotting. The spatial distribution characteristics of mTOR, p-mTOR, HIF-1α, and Collagen I were verified via immunofluorescence techniques. The results demonstrated that the Mingshi Formula significantly decreased myopic refractive error and axial length (p < 0.01), increased choroidal thickness (p < 0.05), downregulated the gene and protein expression of mTOR, p-mTOR, HIF-1α, LDHA, PKM2, MMP2, and α-SMA in response to hypoxia, and upregulated the expression of Collagen I compared to the FDM group. We demonstrated that MingShi formula modulates the mTOR/HIF-1α signaling axis to ameliorate scleral hypoxic metabolic homeostasis, regulate Collagen synthesis, inhibit aberrant extracellular matrix remodeling, and ultimately delay myopia progression.
