> Publications > Regulatory Effects of the Wnt7b/β-Catenin/MMP-2 Signaling Pathway on Scleral Stiffness in Guinea Pigs With Form-Deprivation Myopia

Photorefractor

Publication

March 26, 2026 • ✎ STRIA TECH

Regulatory Effects of the Wnt7b/β-Catenin/MMP-2 Signaling Pathway on Scleral Stiffness in Guinea Pigs With Form-Deprivation Myopia

Topics:

Myopia

Myopia, Refractive Development and Eye Growth

Publication

Investigative Ophthalmology & Visual Science (May 01, 2025) Regulatory Effects of the Wnt7b/β-Catenin/MMP-2 Signaling Pathway on Scleral Stiffness in Guinea Pigs With Form-Deprivation Myopia

Wen B, Li H, Tao H, Ren H, Ma B, Shi M, Chen S, Du J, Cai Z, Zhang J, Guan D, Deng Z

DOI: 10.1167/iovs.66.5.19 >>

This study shows that activating Wnt7b/β-catenin signaling in sclera accelerates collagen I degradation, softens the sclera, and promotes axial elongation and myopic refraction in form-deprived guinea pigs and scleral fibroblasts. Inhibiting Wnt7b/β-catenin partially preserved scleral stiffness and reduced myopic shifts, highlighting this pathway as a mechanistic driver of scleral remodeling in myopia. Refractive state was quantified with Striatech’s Photorefractor, contributing precise, repeated refraction measurements that linked molecular and biomechanical changes to functional myopic outcomes.

Purpose: The development and progression of myopia are influenced by the Wnt7b/β-catenin signaling pathway. This study investigated the specific impacts of this pathway on the biomechanical properties of the sclera by altering the expression of matrix metalloproteinase-2 (MMP-2) to regulate type I collagen (collagen I) levels. Methods: We examined the effects of the Wnt7b/β-catenin signaling pathway and MMP-2 on human fetal scleral fibroblasts (HFSFs) and the sclera of guinea pigs with form-deprivation myopia (FDM). To explore the effects of the Wnt7b/β-catenin pathway and the role of MMP-2 in this context, we treated HFSFs and guinea pig sclera with specific agonists and inhibitors targeting Wnt7b/β-catenin and MMP-2. The expression levels of Wnt7b, MMP-2, and collagen I were subsequently analyzed quantitatively via western blot (WB) analysis, immunofluorescence, and quantitative real-time PCR (qRT-PCR) to assess protein and mRNA changes in response to pathway manipulation. Atomic force microscopy (AFM) was used to measure the elastic modulus of the treated HFSFs and guinea pig sclera to directly evaluate changes in cell and tissue stiffness. In the FDM model, essential ocular parameters such as refractive error and axial length (AL) were also assessed. Results: In vivo and in vitro activation of the Wnt7b/β-catenin signaling pathway significantly upregulated MMP-2 expression, which was accompanied by a notable decrease in collagen I levels. This change led to a reduction in the elastic modulus of both HFSFs and the sclera of guinea pigs with FDM. These significant biomechanical changes in the scleral tissue were indicated by a reduction in stiffness. Alterations in scleral biomechanics were associated with changes in ocular parameters, including an increase in AL and a myopic shift in refraction. Conclusions: The Wnt7b/β-catenin pathway regulates scleral biomechanics by upregulating MMP-2 expression, which leads to increased collagen I degradation and, consequently, an increase in axial elongation and a myopic shift in refractive error.