视网膜波在多巴胺调节视网膜和眼睛发育中的作用

眼球和视网膜的正常发育是保证视觉系统实施其功能的重要基础。视网膜波(RW)和视觉经验依赖的多巴胺能机制，分别在动物睁眼前和睁眼后眼球和视网膜的发育过程中起着关键作用。本项目的研究主题是：RW是如何影响视网膜中唯一产生多巴胺的无长突细胞(DAC)，从而调控眼球和视网膜的发育。首先，我们将培育荧光蛋白标记DAC的转基因小鼠及条件性基因敲除小鼠(使其特定细胞上胆碱能和/或谷氨酸能RW——RW的两个主要成分缺失)。然后，应用电生理、钙成像、光遗传学、形态学及HPLC等技术，研究以下两个问题。一，在以上小鼠，分析作用于DAC上胆碱能和谷氨酸能RW的来源及其对DAC的调控机制；二，在条件性敲除小鼠，研究RW缺失后，多巴胺的合成和释放及眼球的生长与屈光发育的变化。本研究将对RW如何通过调控DAC而影响眼球生长和视网膜的发育形成较完整的认识。同时，有可能对近视的诊治，以及早产儿眼球发育缺陷的治疗提供启示。

The normal development of the eye and retina is an important basis for the visual system to perform its functions. Retinal waves and visual experience-dependent dopaminergic mechanisms play key roles in the development of the eye and retina before and after the eye opening, respectively. The research topic of the proposed study is how retinal waves affect retinal dopaminergic amacrine cells (DACs) and trigger dopamine release which influence retinal and eye development. We will develop transgenic mice in which DACs are labeled with fluorescent proteins, and conditional knockout mice in which cholinergic and/or glutamatergic retinal waves ——the two main components of retinal waves, are eliminated on the specific retinal neurons. Using electrophysiological recording, calcium imaging, optogenetics, immunohistochemistry and high-performance liquid chromatograph (HPLC), we will then study the following two scientific issues. Firstly, we will define the sources of cholinergic and glutamatergic retinal waves acting on developing DACs and their regulatory mechanisms for DAC in the above mice. Secondly, changes in the synthesis and release of dopamine, and ocular growth and refractive development will be investigated in the conditional knockout mice in which cholinergic and/or glutamatergic retinal waves are eliminated. This study will provide a more complete understanding of the role of retinal waves in dopamine regulation of ocular growth and retinal development. It may also provide enlightenment for the diagnosis and treatment of myopia, as well as the treatment of ocular developmental defects in premature infants.