She Man, Li Bing, Li Tao, Hu Qianqian, Zhou Xiaodong
Department of Ophthalmology, Jinshan Hospital of Fudan University, Shanghai 201508, P.R. China.
Central Laboratory, Jinshan Hospital of Fudan University, Shanghai 201508, P.R. China.
Exp Ther Med. 2021 Apr;21(4):371. doi: 10.3892/etm.2021.9802. Epub 2021 Feb 19.
It has been shown that flickering light can affect the development of eyeballs. However, the exact mechanism remains unclear. The ERK1/2-MMP-2 pathway is a classic pathway involved in the modulation of the extracellular matrix (ECM) in cancer tissues. However, to the best of our knowledge, the role of this pathway in modulating the scleral ECM in myopia has not been previously examined. The present study aimed to determine the effects of the ERK1/2-MMP-2 pathway on the formation of flickering light-induced myopia (FLM). Guinea pigs were raised under illumination at a flash rate of 0.5 Hz for 6 weeks to induce FLM. Peribulbar injections of dimethylsulfoxide or PD98059 (an inhibitor of phospho-ERK1/2) were administered starting at the third week of FLM modeling. Refraction was measured prior to and following treatments. The thickness of the posterior sclera (PS) was measured under a light microscope following H&E staining. The mRNA levels of MMP-2 were detected by the reverse transcription-quantitative PCR assay. The expression levels of MMP-2 and ERK1/2 were assayed by western blot and immunohistochemical analyses. Following 6 weeks of treatment, the refraction of the FLM group became more myopic compared with that of the control group, while PD98059 treatment inhibited the changes noted in the refraction. A marked reduction in the thickness of PS was observed in the FLM group, while PD98059 inhibited the remodeling of PS. In addition, the expression levels of MMP-2 and protein levels of phospho-ERK1/2 were increased in the FLM group, while PD98059 significantly inhibited MMP-2 mRNA and protein levels. These results indicated that ERK1/2-MMP-2 may be involved in the formation of FLM in guinea pigs by regulating the remodeling of PS.
研究表明，闪烁光会影响眼球发育。然而，确切机制尚不清楚。ERK1/2-MMP-2通路是参与调节癌组织细胞外基质（ECM）的经典通路。然而，据我们所知，该通路在调节近视巩膜ECM中的作用此前尚未被研究。本研究旨在确定ERK1/2-MMP-2通路对闪烁光诱导性近视（FLM）形成的影响。将豚鼠置于0.5Hz闪光频率的光照下饲养6周以诱导FLM。从FLM建模的第三周开始，球周注射二甲基亚砜或PD98059（磷酸化ERK1/2的抑制剂）。在治疗前后测量屈光。在苏木精-伊红（H&E）染色后，在光学显微镜下测量后巩膜（PS）的厚度。通过逆转录定量PCR测定法检测MMP-2的mRNA水平。通过蛋白质印迹和免疫组织化学分析测定MMP-2和ERK1/2的表达水平。治疗6周后，与对照组相比，FLM组的屈光变得更加近视，而PD98059治疗抑制了屈光的变化。在FLM组中观察到PS厚度明显降低，而PD98059抑制了PS的重塑。此外，FLM组中MMP-2的表达水平和磷酸化ERK1/2的蛋白水平增加，而PD98059显著抑制MMP-2的mRNA和蛋白水平。这些结果表明，ERK1/2-MMP-2可能通过调节PS的重塑参与豚鼠FLM的形成。
