Department of Ophthalmology, Zhongshan Hospital Affiliated to Fudan University, Shanghai, China.
Department of Ophthalomolgy, West China Hospital, Sichuan University, Chengdu, China.
Invest Ophthalmol Vis Sci. 2023 Oct 3;64(13):15. doi: 10.1167/iovs.64.13.15.
The purpose of this study was to investigate the underlying molecular mechanism of lens-induced myopia (LIM) through transcriptome and proteome analyses with a modified mouse myopia model.
Four-week-old C57BL/6J mice were treated with a homemade newly designed -25 diopter (D) lens mounting by a 3D printing pen before right eyes for 4 weeks. Refraction (RE) and axial dimensions were measured every 2 weeks. Retinas were analyzed by RNA-sequencing and data-independent acquisition liquid chromatography tandem mass spectrometry. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation, and STRING databases were used to identify significantly affected pathways in transcriptomic and proteomic data sets. Western blot was used to detect the expression of specific proteins.
The modified model was accessible and efficient. Mice displayed a significant myopic shift (approximately 8 D) following 4 weeks' of lens treatment. Through transcriptomics and proteomics analysis, we elucidated 175 differently expressed genes (DEGs) and 646 differentially expressed proteins (DEPs) between binoculus. The transcriptomic and proteomic data showed a low correlation. Going over the mRNA protein matches, insulin like growth factor 2 mRNA binding protein 1 (Igf2bp1) was found to be a convincing biomarker of LIM, which was confirmed by Western blot. RNA-seq and proteome profiling confirmed that these two "omics" data sets complemented one another in KEGG pathways annovation. Among these, metabolic and human diseases pathways were considered to be correlated with the LIM forming process.
The newly constructed LIM model provides a useful tool for future myopia research. Combining transcriptomic and proteomic analysis may potentially brighten the prospects of novel therapeutic targets for patients with myopia.
本研究通过对改良型小鼠近视模型进行转录组和蛋白质组分析，探讨晶状体诱导近视（LIM）的潜在分子机制。
4 周龄 C57BL/6J 小鼠使用自制的新型 -25 屈光度（D）透镜安装在 3D 打印笔上，4 周前右眼进行治疗。每 2 周测量一次屈光度（RE）和眼轴长度。通过 RNA 测序和数据非依赖性采集液相色谱串联质谱分析视网膜。使用基因本体论（GO）、京都基因与基因组百科全书（KEGG）注释和 STRING 数据库来鉴定转录组和蛋白质组数据集中受显著影响的途径。Western blot 用于检测特定蛋白质的表达。
改良模型易于操作且高效。经过 4 周的透镜处理，小鼠表现出明显的近视漂移（约 8 D）。通过转录组学和蛋白质组学分析，我们在双眼之间鉴定出 175 个差异表达基因（DEGs）和 646 个差异表达蛋白（DEPs）。转录组和蛋白质组数据显示出低相关性。在 mRNA-蛋白质匹配中，胰岛素样生长因子 2 mRNA 结合蛋白 1（Igf2bp1）被发现是 LIM 的一个有说服力的生物标志物，Western blot 进一步证实了这一点。RNA-seq 和蛋白质组谱分析证实，这两个“组学”数据集在 KEGG 途径创新方面相互补充。其中，代谢和人类疾病途径被认为与 LIM 形成过程相关。
新构建的 LIM 模型为未来的近视研究提供了有用的工具。结合转录组和蛋白质组分析可能为近视患者的新型治疗靶点带来希望。
