光照中色觉和亮度信号对眼球屈光发育的调控及光照调控眼球正视化的分子机制

光照环境影响眼球的屈光发育过程，不同波长的单色光可以诱导出近视或远视，但机制不明。现有光照对屈光发育的调控理论不能完全解释动物实验中观察到的屈光变化。我们提出，光照中的色觉或亮度信号对眼球屈光发育具有双向调控作用，且这一过程是由视网膜ON传导通路传递，通过多巴胺-AC-cAMP-PKA以及褪黑激素-GC-cGMP-PKG通路进行调控。本课题将以豚鼠为研究对象，用不同光照模式模拟色觉或亮度信号输入，动态测量各时间点眼球生物学参数，来阐明不同光照模式下，单色光调控眼球屈光发育的双向模式；通过阻断ON通路或改变眼内多巴胺和褪黑激素间的动态平衡，初步揭示ON传导通路以及多巴胺和褪黑激素如何交互作用调控眼球的正视化过程；在光照诱导的近视或远视豚鼠的巩膜成纤维细胞中，通过抑制AC或GC的活性，研究光照调控眼球正视化的具体信号通路。本课题的实施为今后从光生物学效应或药物研发来防治近视提供依据和方法。

Different lighting environments can affect the refraction of the eye, and increasing outdoor lighting can prevent myopia. The studies found that different wavelengths of monochromatic lights can induce myopia or hyperopia, but the mechanisms are obscured. The existing theories of light regulation on refractive development can’t fully explain the observed changes in animal experiments. We propose that the color or luminance signals derived from light have bidirectional effects on the development of eye refraction, and this process is mediated by the retinal ON pathway through the Dopamine-AC-cAMP-PKA and Melatonin-GC-cGMP-PKG pathways. This project will raise guinea pigs under different lights conditions which simulate color or luminance signal inputs, dynamically measure the biological parameters of the eyeballs at each time point and clarify the bidirectional mode of monochromatic light regulating eye refractive development. By blocking the ON pathway or changing the dynamic balance between dopamine and melatonin in the eye, the ON pathway and how dopamine and melatonin work together to regulate the emmetropization of the eye were investigated. In the scleral fibroblasts cultured from light-induced myopic or hyperopia guinea pigs, the expression of AC or GC will be inhibited to study the specific signal pathways of emmetropization regulated by illumination. The implementation of this project will provide a basis and method for the prevention and treatment of myopia from the aspects of lights’ photobiological effects or novel drug development in the future.