Vasoactive intestinal peptide attenuates form-deprivation myopia in guinea pigs by suppressing the Wnt/β-catenin pathway along the retina-choroid-scleral axis.

PURPOSE: To investigate whether intravitreal vasoactive intestinal peptide (VIP) attenuates form-deprivation myopia (FDM) in a dose-dependent manner in guinea pigs and to determine whether this effect is mediated through regulation of the scleral Wnt/β-catenin signaling pathway.

METHODS

A customized latex-balloon facemask was used to induce monocular FDM by covering the right eye, with the left eye remaining uncovered and serving as an internal self-control (SC). Fifty-four 3-week-old guinea pigs were randomly assigned to FDM without injection, FDM with intravitreal VIP (six subgroups receiving 0.1-10000 pmol VIP), or FDM with intravitreal saline. Refraction and axial length were measured at baseline and at weeks 2 and 4 to establish dose-response relationships and identify the optimal VIP concentration. Using the same FDM protocol, 45 additional 3-week-old guinea pigs were allocated to three groups: FDM, FDM + intravitreal VIP (100 pmol), and FDM + saline. Ocular biometric measurements were obtained at baseline and at weeks 2 and 4 during follow-up. Eyes were then enucleated for hematoxylin-eosin histological analysis of the retina, choroid, and sclera, as well as immunohistochemical assessment of β-catenin expression. Primary scleral fibroblasts were isolated to evaluate VIP-induced changes in Wnt3 and β-catenin expression using immunofluorescence and qRT-PCR.

RESULTS

Both refractive error and axial length demonstrated a clear VIP dose-dependent response. Form deprivation induced aberrant activation of the scleral Wnt/β-catenin signaling pathway, which was significantly suppressed by VIP treatment. Moreover, VIP administration partially restored the disrupted collagen fibril organization characteristic of myopic sclera.

CONCLUSIONS

VIP effectively slows the progression of FDM by downregulating aberrant Wnt/β-catenin signaling.