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绿光诱导近视小鼠模型中的视网膜神经退行性变。

Retinal neurodegeneration in a mouse model of green-light-induced myopia.

机构信息

Department of Ophthalmology, Zhongshan Hospital, Fudan University, Shanghai, China.

Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

出版信息

Exp Eye Res. 2022 Oct;223:109208. doi: 10.1016/j.exer.2022.109208. Epub 2022 Aug 6.

Abstract

PURPOSE

To determine the retinal neurodegeneration occurring in mice with green-light-induced myopia.

METHODS

Four-week-old mice were raised under white or green light (peak at 510 nm). Refraction and axial length (AL) were measured before and after eight weeks of illumination treatment. TUNEL staining, electron microscopy and the Visual Cliff test were performed to identify the conditions of retinal degeneration. The distinct protein signatures of retina tissues were quantified by mass spectrometry (MS) - based proteomics, and analyzed by Gene Set Enrichment Analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation and STRING database. Western blot was used to detect the expression of the specific protein.

RESULTS

Green-light-induced myopia was developed in mice after eight weeks of illumination treatment. Apoptosis and the abnormality in ultrastructure and visual function of mice exposed to green light were found through morphological and behavioral experiment, indicating retinal degeneration. The altered proteome was associated with Human Phenotype Ontology (HPO) annotations sets of 'abnormality of visual evoked potentials' and 'neuronal loss in central nervous system'. KEGG annotation demonstrated the altered pathway of the dopaminergic synapse in the myopic mice. STRING database was utilized with an effort to identify the molecular pathways within, and dysregulation of mitochondrial metabolism was revealed.

CONCLUSIONS

Overall, our study revealed molecular differences and pathways underlying retinal degeneration in the mouse model of green-light-induced myopia. These findings might provide insights into further research into myopia prevention and control.

摘要

目的

确定绿光诱导近视小鼠的视网膜神经退行性变。

方法

将 4 周龄的小鼠置于白光或绿光(峰值为 510nm)下饲养。在光照处理 8 周前后测量屈光度和眼轴(AL)。通过 TUNEL 染色、电子显微镜和视觉悬崖试验来确定视网膜退化的情况。通过基于质谱(MS)的蛋白质组学定量分析视网膜组织的特异蛋白特征,并通过基因集富集分析(GSEA)、京都基因与基因组百科全书(KEGG)注释和 STRING 数据库进行分析。采用 Western blot 检测特定蛋白的表达。

结果

经过 8 周光照处理后,小鼠出现绿光诱导性近视。形态学和行为学实验发现,暴露于绿光下的小鼠发生凋亡以及超微结构和视觉功能异常,提示视网膜退化。改变的蛋白质组与人类表型本体(HPO)注释集的“视觉诱发电位异常”和“中枢神经系统神经元丢失”相关。KEGG 注释表明,近视小鼠中的多巴胺能突触发生了改变。利用 STRING 数据库试图识别其中的分子途径,揭示了线粒体代谢的失调。

结论

综上所述,我们的研究揭示了绿光诱导性近视小鼠视网膜退化的分子差异和途径。这些发现可能为近视预防和控制的进一步研究提供思路。

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