ZhuJing Pill retards lens-induced myopia progression by improving ciliary muscle mitochondrial function via KEAP1/NRF2-TGF-β axis.

To evaluate the anti-myopic effect of ZhuJing Pill (ZJP) in a guinea pig model of lens-induced myopia (LIM) and investigate whether ZJP attenuates ciliary muscle fibrosis by improving mitochondrial function, regulating KEAP1/NRF2 antioxidant defense, and inhibiting TGF-β-related fibrotic signaling. One hundred and forty-four male guinea pigs (2 weeks old) were randomly assigned to four groups: a normal control (NC), a LIM model, a ZJP treatment, and a sham (SHAM). All but NC wore - 6.00 D lenses on the right eye to induce myopia. ZJP was orally administered at 5.0 g/kg/day for 4 or 6 weeks. Refractive error, axial length, and ciliary muscle structure were measured by A-scan ultrasonography and OCT. Ciliary muscle tissues were analyzed using HE, Masson's trichrome, and Sirius Red staining. Mitochondrial membrane potential, Ca2⁺ homeostasis, and DRP1/OPA1 expression were assessed, along with oxidative stress markers and expression of KEAP1, NRF2, TGF-β, α-SMA, and Collagen-I. At both time points, LIM and SHAM groups showed significant axial elongation, myopic shifts, ciliary muscle structural abnormalities, mitochondrial dysfunction, elevated ROS and MDA, decreased SOD and GSH-Px activities, upregulation of KEAP1, TGF-β, α-SMA, and Collagen-I, and DRP1/OPA1 imbalance. ZJP treatment significantly attenuated these changes, restored ciliary muscle structure and mitochondrial function, reduced oxidative stress, normalized KEAP1/NRF2 expression, and suppressed TGF-β-mediated fibrotic markers. ZJP alleviates LIM-induced myopia by improving mitochondrial function, restoring KEAP1/NRF2 antioxidant defense, and inhibiting TGF-β-mediated ciliary muscle fibrosis. These findings support ZJP as a potential therapeutic agent for myopia prevention and highlight ciliary muscle fibrosis as a key pathological mechanism.