视网膜钙离子通道在近视发生发展中的作用研究

Myopia is the leading causes of refractive error worldwide, and its pathogenesis is still poorly understood. Many studies have found that decrease of retinal dopamine was associated wtih myopia, but the mechanism of the reduction of dopamine in myopia is unknown. In our preliminary studies, we found that retinal calcium signaling was associated with myopia in both genetic and aniaml experiments, and reveal genetic mutations of calcium channel genes in patients with pathological myopia. Previous studies and our preliminary studies indicate that calcium channels are involved in retinal dopamine releasing, and dopamine plays a critical role in myopia develoment. Thus, we proposed our hypothesis that “dysfunction of calcium channels result in decrease of retinal dopamine level, then inhibit the function of the retinal dopamine receptor, and finally lead to the occurrence and development of myopia.” To testify this hypothesis, firstly, we will investigate the distribution and fucntion of susceptibility genes associated calcium channles in vitro expriment. Secondly, we will identify expression and functional changes of calcium channels for retinal dopaminergic amacrine cell during form deprivation myopia. Then we clarify whether the inhibition of calcium channels’ function may reslut in the occurrence and development of myopia. Finally, to clarify whether the calcium channel can affect the dopamine release of retinal dopaminergic cells, and elucidates pathogenesis of calcium channels in myopia. Our research wiil offer a new perspective for the pathogenesis of myopia, especially the pathological myopia. Our results will provide new ideas and theoretical basis for clinical prevention, intervention and treatment of myopia.

近视是常见的一种屈光不正，其致病机制尚未明确，研究已发现视网膜多巴胺的减少可能和近视相关，但多巴胺减少的机制仍未明了。在我们前期工作中，通过遗传学研究及动物实验，发现视网膜钙信号与近视相关，病理性近视患者钙离子通道基因发生突变。文献报道表明钙离子通道可能影响视网膜多巴胺的释放，据此我们提出“视网膜钙离子通道基因异常可导致多巴胺的释放减少，进而抑制了视网膜多巴胺受体的功能，最后导致近视的发生发展”的科学假说。我们拟进行以下研究证实该假说：明确钙离子通道突变基因对钙通道表达及功能的影响；在近视模型中明确视网膜多巴胺能无长突细胞钙通道的表达以及功能是否受到影响；明确抑制视网膜钙通道是否影响近视的发生发展；明确钙离子通道是否影响视网膜多巴胺能无长突细胞多巴胺释放，以阐明钙通道在近视中的作用机制。为近视特别是病理性近视的发病机制开辟新的研究角度，进而为临床预防、干预和治疗近视提供新思路和理论依据。

近视是常见的一种屈光不正，其致病机制尚未明确。前期通过遗传学研究及动物实验，发现视网膜钙信号与近视相关，病理性近视患者钙离子通道基因发生突变。本项目通过对视网膜钙离子通道信号的研究，明确钙通道信号在近视中的作用机制。在形觉剥夺小鼠中验证钙通道相关基因表达有所变化；使用钙离子通道的特异性阻滞剂和激动剂，然后观察其对小鼠正常屈光发育的影响，结果发现钙离子通道参与了近视的形成及形觉剥夺性近视进展；结合钙离子指示剂转基因小鼠，发现剥夺眼水平细胞的高钙离子浓度的细胞数量明显下降，表明了水平细胞钙离子浓度与近视有明确关联。综上，提示钙离子通道参与了近视形成，可能影响到水平细胞功能所致，但具体机制还有待深入阐明。