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 0.1-10000pmol 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 (100pmol), 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.
You et al. (Tue,) studied this question.