Intraperitoneal Injection of MCC950 Inhibits the Progression of Myopia in Form-Deprivation Myopic Mice

Abstract

Myopia, one of the most prevalent ocular diseases worldwide, is projected to affect nearly half of the global population by 2050. The main cause of myopia in most patients is axial myopia, which primarily occurs due to the elongation of the eyeball, driven by changes in the extracellular matrix (ECM) of scleral cells. Previous studies have shown that NLRP3, an important inflammatory mediator, plays a critical role in regulating the expression of MMP-2 in the sclera. This, in turn, leads to a decrease in the expression of Collagen-1, a major component of the scleral ECM, triggering the remodeling of the scleral ECM. This study aimed to investigate the effect of MCC950, an inhibitor of NLRP3, on the progression of myopia using a mouse form-deprivation myopia (FDM) model. The FDM mouse model was constructed by subjecting three-week-old C57BL/6J mice to form-deprivation. The mice were divided into experimental (n = 10/group; FDM2M, FDM4M, FDM2W, and FDM4W) and control groups (n = 5/group). The experimental groups were further categorized based on the duration of form deprivation (2 and 4 weeks, labeled as 2 and 4, respectively) and the type of injection received (MCC950 or saline, labeled as M and W, respectively). MCC950 was injected at a concentration of 50 mg/mL, with a dose of 10 mg per kilogram of body weight. Meanwhile, the saline group received the same volume of saline. Refraction and axial length measurements were performed for each eye. The expression levels of NLRP3, caspase-1, IL-1β, IL-18, MMP-2, and Collagen-1 in the sclera were assessed using immunohistochemistry and Western blotting. The intraperitoneal injection of MCC950 did not significantly affect refraction or axial length in normal mice (p > 0.05). However, in FDM mice, MCC950 attenuated the elongation of the axial length and resulted in a smaller shift towards myopia compared to the saline group (FDM4M vs. FDM4W, p = 0.03 and p < 0.05, respectively). MCC950 decreased MMP-2 expression (p < 0.05) but increased Collagen-1 expression (p < 0.05) in the experimental eyes when compared to the saline group. Within the MCC950 group, the expression of MMP-2 was increased in the experimental eyes at 4 weeks (p < 0.05), while that of Collagen-1 was decreased (p < 0.05), which is consistent with changes in refractive error. Immunohistochemical analysis yielded similar results (p < 0.05). MCC950 also reduced the expression levels of NLRP3 (p = 0.03), caspase-1 (p < 0.05), IL-1β (p < 0.05), and IL-18 (p < 0.05) in the experimental eyes compared to the saline group. Within the MCC950 group, the expression levels of NLRP3 and caspase-1 were comparable between the experimental and control eyes (p > 0.05), whereas IL-18 expression was higher in experimental eyes (p < 0.05). IL-1β expression was higher in the experimental eyes only at week 4 (p < 0.05). The intraperitoneal injection of MCC950 can inhibit the progression of myopia in FDM mice, possibly by regulating collagen remodeling in the sclera through the NLRP3-MMP-2 signaling pathway. Therefore, MCC950 holds promise as a potential therapeutic agent for controlling the progression of myopia.