Wu Jinsong, Zhao Yanzhi, Fu Yanmei, Li Shurong, Zhang Xu
Department of Pediatric Ophthalmology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
The First Clinical Medical College, Nanchang University, Nanchang, Jiangxi 330000, P.R. China.
Exp Ther Med. 2021 May;21(5):495. doi: 10.3892/etm.2021.9926. Epub 2021 Mar 17.
Lumican serves an important role in the maintenance of sclera biomechanical properties. However, whether lumican expression is altered in myopia and the mechanisms of action involved are unknown. In the present study, the expression of lumican in cultured scleral fibroblasts and in the scleral tissue of a rat model of form-deprivation myopia was assessed. It was confirmed that diopter was decreased, whereas axial length was increased in modeled eyes relative to normal control eyes, indicating that the model of myopia was successfully established. These pathologic changes were accompanied by the upregulation of lumican and tissue inhibitor of metalloproteinases (TIMP)-2, as well as the downregulation of matrix metalloproteinase (MMP)-2 and MMP-14. The same trends in TIMP-2, MMP-2 and MMP-14 expression were observed when lumican was overexpressed in cultured scleral fibroblasts. Additionally, cell proliferation decreased whereas apoptosis increased compared with those of control cells. Inhibiting lumican expression had no effect on cell proliferation or apoptosis, but stimulated the expression of MMP-2 and MMP-14 while decreasing that of TIMP-2. The results suggested that lumican overexpression contributed to myopia by promoting apoptosis in scleral fibroblasts via the modulation of TIMP-2, MMP-2 and MMP-14 expression.
角膜蛋白聚糖在维持巩膜生物力学特性中发挥重要作用。然而,角膜蛋白聚糖的表达在近视中是否改变以及所涉及的作用机制尚不清楚。在本研究中,评估了角膜蛋白聚糖在培养的巩膜成纤维细胞以及形觉剥夺性近视大鼠模型巩膜组织中的表达。结果证实,与正常对照眼相比,建模眼的屈光度降低,而眼轴长度增加,表明近视模型成功建立。这些病理变化伴随着角膜蛋白聚糖和金属蛋白酶组织抑制剂(TIMP)-2的上调,以及基质金属蛋白酶(MMP)-2和MMP-14的下调。当在培养的巩膜成纤维细胞中过表达角膜蛋白聚糖时,观察到TIMP-2、MMP-2和MMP-14表达呈现相同趋势。此外,与对照细胞相比,细胞增殖减少而凋亡增加。抑制角膜蛋白聚糖表达对细胞增殖或凋亡没有影响,但刺激了MMP-2和MMP-14的表达,同时降低了TIMP-2的表达。结果表明,角膜蛋白聚糖过表达通过调节TIMP-2、MMP-2和MMP-14的表达促进巩膜成纤维细胞凋亡,从而导致近视。