Abstract：
The ciliary muscle constitutes a crucial element in refractive regulation. Investigating the pathophysiological mechanisms within the ciliary muscle during excessive contraction holds significance in treating ciliary muscle dysfunction. A guinea pig model of excessive contraction of the ciliary muscle induced by drops pilocarpine was employed, alongside the primary ciliary muscle cells was employed in in vitro experiments. The results of the ophthalmic examination showed that pilocarpine did not significantly change refraction and axial length during the experiment, but had adverse effects on the regulatory power of the ciliary muscle. The current data reveal notable alterations in the expression profiles of hypoxia inducible factor 1 (HIF-1α), ATP2A2, P53, α-SMA, Caspase-3, and BAX within the ciliary muscle of animals subjected to pilocarpine exposure, alongside corresponding changes observed in cultured cells treated with pilocarpine. Augmented levels of ROS were detected in both tissue specimens and cells, culminating in a significant increase in cell apoptosis in in vivo and in vitro experiments. Further examination revealed that pilocarpine induced an increase in intracellular Ca2+ levels and disrupted MMP, as evidenced by mitochondrial swelling and diminished cristae density compared to control conditions, concomitant with a noteworthy decline in antioxidant enzyme activity. However, subsequent blockade of Ca2+ channels in cells resulted in downregulation of HIF-1α, ATP2A2, P53, α-SMA, Caspase-3, and BAX expression, alongside ameliorated mitochondrial function and morphology. The inhibition of Ca2+ channels presents a viable approach to mitigate ciliary cells damage and sustain proper ciliary muscle function by curtailing the mitochondrial damage induced by excessive contractions.
摘要：
睫状肌构成屈光调节的关键因素。研究过度收缩期间睫状肌内的病理生理机制对治疗睫状肌功能障碍具有重要意义。采用毛果芸香碱滴剂引起的睫状肌过度收缩的豚鼠模型，与原代睫状肌细胞一起用于体外实验。眼科检查结果显示,毛果芸香碱在实验过程中没有明显改变屈光度和眼轴长度,但对睫状肌的调节能力有不利影响。目前的数据揭示了缺氧诱导因子1(HIF-1α)表达谱的显著改变，ATP2A2,P53,α-SMA,接受毛果芸香碱暴露的动物的睫状肌内的Caspase-3和BAX，在用毛果芸香碱处理的培养细胞中观察到相应的变化。在组织标本和细胞中检测到增加的ROS水平，在体内和体外实验中，细胞凋亡显着增加。进一步的检查显示，毛果芸香碱诱导细胞内Ca2+水平的增加和MMP的破坏，与对照条件相比，线粒体肿胀和cr密度减少证明了这一点，伴随着抗氧化酶活性的显著下降。然而,随后阻断细胞中的Ca2+通道导致HIF-1α的下调，ATP2A2,P53,α-SMA,Caspase-3和BAX表达，同时改善线粒体功能和形态。Ca2通道的抑制提供了一种可行的方法，可以通过减少过度收缩引起的线粒体损伤来减轻睫状细胞损伤并维持适当的睫状肌功能。
