自然光对幼猴离焦性近视的影响及其视网膜机制研究

Recent studies by applicants have shown that outdoor light can significantly slow down the development and progression of myopia in developmental rhesus monkeys. However, the mechanism of the inhibition by outdoor exposure are unclear. And also, the effects of simulated natural light by artificial lights on myopia inhibition are unknown. This project intends to observe biomechanical properties and refractive status dynamically and use DNA methylation, molecular probes and other research methods to explore the development of rhesus monkey eyeball growth and refractive status under outdoor light or artificial natural light with different time pattern. DNA methylation of differentially expressed genes in retina as well as changes of GRID1 and Egr-1 genes and their related proteins in retinal amacrine cells and bipolar cells will be studied to understand the effects and regulation by different light signals, so as to further understand the possible mechanism of myopia and to provide a new theoretical basis and methods for myopia prevention and control.

申请者最近的研究表明,户外自然光可明显减缓发育期恒河猴近视的发生和发展，但这种近视减缓作用与户外自然光暴露时间的关系及其机制还不清楚；人工智能模拟自然光是否与户外自然光一样能有效减缓近视的发生与发展也不清楚。本项目拟用屈光状态动态观察、DNA甲基化、分子探针等研究方法，探讨不同时间模式户外自然光和人工智能模拟自然光信号作用下，恒河猴离焦性近视眼球生长和屈光状态发育过程，视网膜组织差异表达基因的DNA甲基化程度以及视网膜无长突细胞、双极细胞GRID1、Egr-1基因及其相关蛋白之间的变化，了解不同时间模式自然光和人工智能模拟自然光影响眼轴延长、屈光状态变化及其调控过程，从而进一步了解近视眼发生的可能机制,为近视防控提供新的理论依据和方法。

本项目用恒河猴建立离焦性近视动物模型，采用屈光状态动态观察、DNA甲基化、分子探针和蛋白质时空效应等研究方法，探讨不同时间模式户外自然光和人工智能模拟自然光信号作用下，恒河猴离焦性近视眼球生长和屈光状态发育过程，视网膜组织差异表达基因的DNA甲基化程度，以及视网膜细胞GRID1、Egr-1基因及其相关蛋白之间的变化。结果发现：1）不同时间模式户外自然光和人工智能模拟自然光信号作用下，恒河猴玻璃体腔长度的延长减少，明显减缓近视发展；2）不同时间模式户外自然光和人工智能模拟自然光信号作用下，离焦性近视恒河猴视网膜组织基因转录水平和表观遗传学发生改变；3）不同时间模式户外自然光和人工智能模拟自然光信号作用下，可能通过引起视网膜组织Col1a1和Mmp2基因表达变化,调控恒河猴屈光状态发育过程。本项目进一步明晰了不同时间模式自然光和人工智能模拟自然光影响眼轴延长、屈光状态变化及其调控过程，进一步了解近视眼发生、发展的可能机制,为进一步完善青少年近视防控的公共卫生策略提供理论依据和方法。