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豚鼠负透镜诱导近视中睫状肌内钾离子离子平衡紊乱。

Disrupted potassium ion homeostasis in ciliary muscle in negative lens-induced myopia in Guinea pigs.

机构信息

Shandong University of Traditional Chinese Medicine, Jinan, 250014, China.

Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Disease in Universities of Shandong, Eye Institute of Shandong University of Traditional Chinese Medicine, Jinan, 250002, China.

出版信息

Arch Biochem Biophys. 2020 Jul 30;688:108403. doi: 10.1016/j.abb.2020.108403. Epub 2020 May 11.

Abstract

Myopia is a main cause of preventable or treatable visual impairment, it has become a major public health issue due to its increasingly high prevalence worldwide. Currently, it is confirmed that the development of myopia is associated with the disorders of accommodation. As a dominant factor for accommodation, ciliary muscle contraction/relaxation can regulate the physiological state of the lens and play a crucial role in the development of myopia. To investigate the relationship between myopia and ciliary muscle, the guinea pigs were randomly divided into a normal control (NC) group and a negative lens-induced myopia (LIM) group, and the animals in each group were further randomly assigned into 2-week (n = 18) and 4-week (n = 21) subgroups in accordance with the duration of myopic induction of 2 and 4 weeks, respectively. In the present study, right eyes of the animals in LIM group were covered with -6.0 D lenses to induce myopia. Next, we performed the haematoxylin and eosin (H&E) staining to observe the pathological change of ciliary muscle, determined the contents of adenosine triphosphate (ATP) and lactate acid (LA), and measured the Na/K-ATPase expression and activity in ciliary muscles in both NC and LIM groups. Moreover, we also analyzed the potassium ion (K) flux in ciliary muscles from 4-week NC and LIM guinea pigs. As a result, we found that the arrangements of ciliary muscles in LIM guinea pigs were broken, dissolved or disorganized; the content of ATP decreased, whereas the content of LA increased in ciliary muscles from LIM guinea pigs. Monitoring of K flux in ciliary muscles from LIM guinea pigs demonstrated myopia-triggered K influx. Moreover, we also noted a decreased expression of Na/K-ATPase (Atp1a1) at both mRNA and protein levels and reduced activity in ciliary muscles from LIM guinea pigs. Overall, our results will facilitate the understanding of the mechanism associated with inhibitory Na/K-ATPase in lens-induced myopia and which consequently lead to the disorder of microenvironment within ciliary muscles from LIM guinea pigs, paving the way for a promising adjuvant approach in treating myopia in clinical practice.

摘要

近视是可预防或可治疗的视力损害的主要原因,由于其在全球范围内的患病率越来越高,已成为一个主要的公共卫生问题。目前已证实,近视的发展与调节障碍有关。睫状肌的收缩/松弛作为调节的主要因素,可以调节晶状体的生理状态,在近视的发展中起着至关重要的作用。为了研究近视与睫状肌的关系,将豚鼠随机分为正常对照组(NC)和负透镜诱导近视组(LIM),每组动物进一步根据 2 周(n=18)和 4 周(n=21)诱导近视的时间随机分为 2 周亚组和 4 周亚组。在本研究中,LIM 组动物的右眼用-6.0 D 透镜遮盖以诱导近视。然后,我们进行了苏木精和伊红(H&E)染色,以观察睫状肌的病理变化,测定三磷酸腺苷(ATP)和乳酸(LA)的含量,并测定 NC 和 LIM 组睫状肌中 Na/K-ATP 酶的表达和活性。此外,我们还分析了来自 4 周 NC 和 LIM 豚鼠的睫状肌中的钾离子(K)通量。结果发现,LIM 豚鼠的睫状肌排列紊乱、溶解或紊乱;LIM 豚鼠睫状肌中的 ATP 含量减少,而 LA 含量增加。监测 LIM 豚鼠睫状肌中的 K 通量表明近视引起的 K 内流。此外,我们还注意到 LIM 豚鼠睫状肌中 Na/K-ATP 酶(Atp1a1)的表达在 mRNA 和蛋白水平均降低,活性降低。总之,我们的研究结果将有助于理解与晶状体诱导近视相关的抑制性 Na/K-ATP 酶的机制,以及 LIM 豚鼠睫状肌内微环境紊乱的机制,为临床治疗近视提供一种有前途的辅助方法。

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