Kang Longdan, Ikeda Shin-Ichi, Yang Yajing, Jeong Heonuk, Chen Junhan, Zhang Yan, Negishi Kazuno, Tsubota Kazuo, Kurihara Toshihide
Laboratory of Photobiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan.
Department of Ophthalmology, The First Hospital of China Medical University, Shenyang, 110001, China.
Eye Vis (Lond). 2023 Nov 1;10(1):44. doi: 10.1186/s40662-023-00361-2.
Recent studies have indicated a strong correlation between endoplasmic reticulum (ER) stress and myopia and that eyedrops containing the ER stress inducer tunicamycin (Tm) can induce myopic changes in C57BL/6 J mice. Therefore, this study aimed to create a new myopia model using Tm eyedrops and to explore the mechanism of ER stress-mediated myopia development.
Three-week-old C57BL/6 J mice were treated with different concentrations (0, 25, 50, and 100 μg/mL) and/or number of applications (zero, one, three, and seven) of Tm eyedrops. Refraction and axial length (AL) were measured before and one week after Tm treatment. Scleral collagen alterations were evaluated under polarised light after picrosirius red staining. ER stress-related indicators, such as the expression of collagen I and cleaved collagen were detected using Western blotting.
Compared with the control group, mice administered eyedrops with 50 μg/mL Tm only once showed the greatest myopic shifts in refraction and AL elongation and reduced scleral expression of collagen I. Picrosirius red staining showed a lower percentage of bundled collagen in the Tm group. Expression of ER-stress indicators increased in the Tm groups. Furthermore, optimised administration of Tm induced matrix metalloproteinase-2 (MMP2) expression in the sclera, which plays a major role in collagen degradation.
We have demonstrated that ER stress in the sclera is involved in myopia progression. Tm eyedrops induced myopic changes, loosening of the scleral collagen and decreased expression of collagen I. This process may be associated with ER stress in the sclera, which upregulates the expression of MMP2 leading to collagen degradation.
最近的研究表明内质网（ER）应激与近视之间存在密切关联，并且含有ER应激诱导剂衣霉素（Tm）的眼药水可诱导C57BL/6 J小鼠发生近视性改变。因此，本研究旨在使用Tm眼药水建立一种新的近视模型，并探讨ER应激介导的近视发展机制。
对3周龄的C57BL/6 J小鼠使用不同浓度（0、25、50和100μg/mL）和/或不同给药次数（零次、一次、三次和七次）的Tm眼药水进行处理。在Tm处理前及处理后1周测量屈光和眼轴长度（AL）。天狼星红苦味酸染色后在偏光下评估巩膜胶原改变。使用蛋白质免疫印迹法检测ER应激相关指标，如I型胶原和裂解胶原的表达。
与对照组相比，仅单次给予50μg/mL Tm眼药水的小鼠在屈光和AL伸长方面出现最大的近视偏移，且巩膜I型胶原表达降低。天狼星红苦味酸染色显示Tm组中束状胶原的百分比更低。Tm组中ER应激指标的表达增加。此外，优化的Tm给药诱导巩膜中基质金属蛋白酶-2（MMP2）表达，其在胶原降解中起主要作用。
我们已经证明巩膜中的ER应激参与近视进展。Tm眼药水诱导近视性改变、巩膜胶原松弛和I型胶原表达降低。这一过程可能与巩膜中的ER应激有关，后者上调MMP2表达导致胶原降解。
