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利非西呱对透镜诱导近视豚鼠屈光的影响及机制

Effect and mechanism of lificiguat on refraction in guinea pigs with lens-induced myopia

    摘要
  • 摘要:
    目的  探讨利非西呱（YC-1）对透镜诱导近视（LIM）豚鼠屈光发育的影响。
    方法 选择4周龄三色豚鼠27只，分为LIM组、LIM+YC-1组、Normal组，每组9只。LIM组右眼近视造模并注射DMSO溶液；LIM+YC-1组右眼近视造模并注射YC-１溶液；Normal组豚鼠右眼不做任何处理；以上3组豚鼠左眼均不进行任何处理。每周以检影法测量各组豚鼠双眼屈光度，A超法测量各组豚鼠双眼眼轴长度；每周以眼前段照相、眼底照相观察各组豚鼠眼表与眼底变化评估利非西呱对豚鼠的眼部毒性。4周后以Western blot法检测各组豚鼠右眼巩膜中缺氧诱导因子-1α（HIF-1α）、Ⅰ型胶原蛋白（COL1α1）、基质金属蛋白酶-2（MMP-2）、金属蛋白酶组织抑制剂-2（TIMP-2）、α-平滑肌肌动蛋白（α-SMA）的表达量。
    结果 4周时LIM+YC-1组右眼较LIM组右眼屈光度更低、眼轴长度更短（P屈光度 = 0.010，P眼轴 = 0.009）。LIM+YC-1组HIF-1α、α-SMA、MMP-2蛋白表达量较LIM组表达量均降低（PHIF-1α = 0.001，Pα-SMA = 0.001，PMMP-2 = 0.001）；COL1α1、TIMP-2较LIM组表达量增加（PCOL1α1 = 0.033，PTIMP-2 = 0.001）。实验期间未发现玻璃体腔注射利非西呱后对豚鼠造成的眼表损害、眼屈光介质以及眼底改变。
    结论 利非西呱抑制了LIM豚鼠的近视进程，且在短期实验中未见对豚鼠造成的眼部药物性损害。

     

    Abstract:
    Objective  To investigate the effect of lificiguat (YC-1) on refractive development in guinea pigs with lens-induced myopia (LIM).
    Methods Twenty-seven 4-week-old tricolor guinea pigs were selected and divided into the LIM, LIM+YC-1, and Normal groups (n = 9 in each group). The right eyes of the LIM group underwent lens-induced myopia modeling and were injected with DMSO solution; the right eyes of the LIM+YC-1 group underwent modeling and were injected with YC-1 solution; the right eyes of guinea pigs in the Normal group received no treatment. The left eyes in all three groups remained untreated. Refractive error and axial length (AL) of bilateral eyes in all groups were measured weekly using retinoscopy and A-scan ultrasonography, respectively. Anterior segment and fundus photography were performed weekly to assess the ocular toxicity of lificiguat. After 4 weeks, the expression levels of hypoxia-inducible factor-1α (HIF-1α), collagen type I alpha 1 (COL1α1), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinases-2 (TIMP-2), and alpha-smooth muscle actin (alpha-SMA) proteins in the right sclera were detected by Western blot, respectively.
    Results At 4 weeks, the right eyes of animals in the LIM+YC-1 group exhibited significantly lower refractive error (P = 0.010) and shorter axial length (P = 0.009) compared to those in the LIM group. The expression levels of HIF-1α, α-SMA, and MMP-2 proteins in the LIM+YC-1 group were significantly lower than those in the LIM group (P HIF-1α = 0.001, P α-SMA = 0.001, P MMP-2 = 0.001), respectively. Conversely, the expression levels of COLl1α1 and TIMP-2 were significantly higher in the LIM+YC-1 group compared to those in the LIM group (P COL1α1 = 0.033, P TIMP-2 = 0.001). No ocular surface damage, refractive media opacity or fundus changes were observed in any guinea pigs following intravitreal injections of lificiguat during the experimental period.
    Conclusions  Lificiguat effectively inhibits the progression of myopia in LIM guinea pigs. No short-term ocular toxicity is induced by lificiguat throughout the short-term experiment.

     

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