Huang Guangyi, Zhang Shaoyang, Liao Jing, Qin Yuanjun, Hong Yiyi, Chen Qi, Lin Yunru, Li Yue, Lan Lin, Hu Wen, Huang Kongqian, Tang Fen, Tang Ningning, Jiang Li, Shen Chaolan, Cui Ling, Zhong Haibin, Li Min, Lu Peng, Shu Qinmeng, Wei Yantao, Xu Fan
Department of Ophthalmology, the People's Hospital of Guangxi Zhuang Autonomous Region & Guangxi Key Laboratory of Eye Health & Guangxi Health Commission Key Laboratory of Ophthalmology and Related Systemic Diseases Artificial Intelligence Screening Technology &Institute of Ophthalmic Diseases, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, China.
Eye Institute, Eye and ENT Hospital, College of Medicine, Fudan University, Shanghai Key Laboratory of Visual Impairment and Restoration, Science and Technology Commission of Shanghai Municipality, Key Laboratory of Myopia (Fudan University), Chinese Academy of Medical Sciences, National Health Commission, Shanghai, China.
Heliyon. 2024 Feb 24;10(5):e27114. doi: 10.1016/j.heliyon.2024.e27114. eCollection 2024 Mar 15.
Retinal ischemia/reperfusion (I/R) injury is implicated in the etiology of various ocular disorders. Prior research has demonstrated that bone marrow tyrosine kinase on chromosome X (BMX) contributes to the advancement of ischemic disease and inflammatory reactions. Consequently, the current investigation aims to evaluate BMX's impact on retinal I/R injury and clarify its implied mechanism of action.
This study utilized male and female systemic BMX knockout (BMX) mice to conduct experiments. The utilization of Western blot assay and immunofluorescence labeling techniques was employed to investigate variations in the expression of protein and tissue localization. Histomorphological changes were observed through H&E staining and SD-OCT examination. Visual function changes were assessed through electrophysiological experiments. Furthermore, apoptosis in the retina was identified using the TUNEL assay, as well as the ELISA technique, which has been utilized to determine the inflammatory factors level.
Our investigation results revealed that the knockdown of BMX did not yield a significant effect on mouse retina. In mice, BMX knockdown mitigated the negative impact of I/R injury on retinal tissue structure and visual function. BMX knockdown effectively reduced apoptosis, suppressed inflammatory responses, and decreased inflammatory factors subsequent to I/R injury. The outcomes of the current investigation revealed that BMX knockdown partially protected the retina through downregulating phosphorylation of AKT/ERK/STAT3 pathway.
Our investigation showed that BMX reduces AKT, ERK, and STAT3 phosphorylation, reducing apoptosis and inflammation. Thus, this strategy protected the retina from structural and functional damage after I/R injury.
视网膜缺血/再灌注（I/R）损伤与多种眼部疾病的病因有关。先前的研究表明，X染色体上的骨髓酪氨酸激酶（BMX）促进缺血性疾病的进展和炎症反应。因此，本研究旨在评估BMX对视网膜I/R损伤的影响，并阐明其潜在的作用机制。
本研究利用雄性和雌性全身性BMX基因敲除（BMX -/-）小鼠进行实验。采用蛋白质免疫印迹法和免疫荧光标记技术研究蛋白质表达和组织定位的变化。通过苏木精-伊红（H&E）染色和光谱域光学相干断层扫描（SD-OCT）检查观察组织形态学变化。通过电生理实验评估视觉功能变化。此外，使用末端脱氧核苷酸转移酶介导的缺口末端标记（TUNEL）法鉴定视网膜中的细胞凋亡，并采用酶联免疫吸附测定（ELISA）技术测定炎症因子水平。
我们的研究结果显示，敲低BMX对小鼠视网膜没有显著影响。在小鼠中，敲低BMX减轻了I/R损伤对视网膜组织结构和视觉功能的负面影响。敲低BMX有效减少了I/R损伤后的细胞凋亡，抑制了炎症反应，并降低了炎症因子水平。本研究结果表明，敲低BMX通过下调AKT/ERK/STAT3信号通路的磷酸化对视网膜起到部分保护作用。
我们的研究表明，BMX降低AKT、ERK和STAT3的磷酸化，减少细胞凋亡和炎症。因此，该策略保护视网膜免受I/R损伤后的结构和功能损害。
