Department of Ophthalmology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China; Clinical Research Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
Department of Ophthalmology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China; Clinical Research Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
J Proteomics. 2021 Jul 15;243:104248. doi: 10.1016/j.jprot.2021.104248. Epub 2021 May 6.
Myopia is the most common optical disorder in the world, and wavelength defocus induced ametropia and myopia have attracted great attention. The objective was to identify and quantify scleral proteins involved in the response to the wavelength defocus. Guinea pigs were randomly divided into 3 groups that received different lighting conditions for 8 weeks: white light, short wavelength light, and long wavelength light. Refraction and axial length were measured, Hematoxylin-Eosin staining and transmission electron microscope were adopted to observe the scleral structure, and scleral proteome was also detected to analyze protein abundance by employing TMT labeling method. After light stimulation, the long- and short -wavelength light induced myopic and hyperopic effect on the guinea pig's eye and induced distinct protein signature, respectively. 186 dyregulated proteins between the short- and long-wavelength group were identified, which were mainly located in extracellular region and involved in metabolic process. We also found that 5 proteins in the guinea pigs scleras in response to wavelength defocus were also human myopic candidate targets, suggesting functional overlap between dyregulated proteins in scleral upon exposure to wavelength defocus and genes causing myopia in humans. SIGNIFICANCE: Wavelength defocus induces refractive errors and leads to myopia or hyperopia. However, sclera proteomics respond to wavelength defocus is lacking, which is crucial to understanding how wavelength defocus influences refractive development and induces myopia. In this proteome analysis, we identified unique protein signatures response to wavelength defocus in sclera of guinea pigs, identified potential mechanisms contributing to myopia formation, and found that several human myopia-related genes may involve in response to wavelength defocus. The results of this study provide a foundation to understand the mechanisms of myopia and wavelength defocus induced ametropia.
近视是世界上最常见的光学障碍,波长失焦诱导的屈光不正和近视引起了极大的关注。目的是鉴定和量化参与对波长失焦反应的巩膜蛋白。豚鼠被随机分为 3 组,接受不同的光照条件 8 周:白光、短波长光和长波长光。测量屈光度和眼轴长度,采用苏木精-伊红染色和透射电镜观察巩膜结构,并采用 TMT 标记法检测巩膜蛋白质组,以分析蛋白质丰度。在光刺激后,长波长光和短波长光分别诱导豚鼠眼睛产生近视和远视效应,并诱导出不同的蛋白质特征。在短波长和长波长组之间鉴定出 186 个差异表达蛋白,这些蛋白主要位于细胞外区,参与代谢过程。我们还发现,豚鼠巩膜对波长失焦反应的 5 种蛋白也是人类近视的候选靶点,提示在暴露于波长失焦时巩膜中差异表达蛋白与导致人类近视的基因之间存在功能重叠。意义:波长失焦诱导屈光不正,导致近视或远视。然而,巩膜蛋白质组对波长失焦的反应是缺乏的,这对于理解波长失焦如何影响屈光发育和诱导近视至关重要。在这项蛋白质组分析中,我们鉴定了豚鼠巩膜对波长失焦的独特蛋白质特征,确定了导致近视形成的潜在机制,并发现几个与人类近视相关的基因可能参与对波长失焦的反应。本研究的结果为理解近视和波长失焦诱导的屈光不正的机制提供了基础。