γ 氨基丁酸信号通路调控豚鼠实验性近视作用机制研究

It is important for preventing myopia to develop therapeutic agents and to investigate the mechanisms of the agents inhibiting or retarding the progress of myopia. We have previously reported that GABAc antagonists inhibit myopia in the chick myopia model,and that GABAa,GABAb,and GABAc receptors are expressed in different position in the eyes. Basing on our previous studys, in this project, we will investigate the effects of GABAa, GABAb, and GABAc agonists and antaganists on ocular refraction, GABA in the retina, Ca2+ and Cl- iron in the RPE, and MMP2 and type Ⅰ collagen mRNA and protein in the sclera, and expression of GABA receptors in the eye ball in the guinea pig myopia model, in order to understand the targets and mechanisms of GABA agents modulating myopia. We will culture guinea pig RPE cells and sclera fibroblasts, and will treat the cells with different GABA agents, and test the Ca2+ and Cl- iron in the RPE cells, and the MMP2 and type Ⅰ collagen mRNA and protein in sclera fibroblasts, and expression of GABA receptors in the cells, in order to understand whether RPE cells and sclera fibroblasts are the direct targets for GABA agents modulating myopia. By the study, we will get the knowledge about the mechanisms for GABA signal passway modifying myopia. By understanding the mocular mechanisms, we (or others) will be able to develop novel tools and therapeutic agents that can be used as preventive and/or adjunct therapy for controlling myopia progression.

研究探讨阻止或延缓近视进展的药物及其作用机制对于近视眼的防治至关重要。我们前期研究已经发现γ氨基丁酸(GABA)c受体拮抗剂抑制小鸡近视，且GABAa、GABAb和GABAc受体在眼组织分布位置不同。在此基础上，拟通过研究GABAa、GABAb和GABAc受体激动剂和拮抗剂对豚鼠实验性近视眼屈光状态、视网膜GABA含量、视网膜色素上皮(RPE) Ca2+和Cl-离子浓度及巩膜细胞外基质的影响，检测GABA受体在眼组织表达，了解GABA信号通路调控近视的作用部位和机制；通过研究GABA类药物对体外培养RPECa2+和Cl-离子浓度及巩膜细胞外基质合成的影响，检测 GABA受体在细胞中表达，明确RPE和巩膜细胞是否为GABA类药物直接作用的靶点。通过研究，明确视网膜、RPE和巩膜在GABA信号通路调控近视中的作用，阐明GABA受体拮抗剂抑制近视的作用靶点和机制，为研制新型抗近视药物提供新思路。

研究探讨阻止或延缓近视进展的药物及其作用机制对于近视眼的防治至关重要。我们前期研究已经发现γ 氨基丁酸(GABA)c 受体拮抗剂抑制小鸡近视，且GABAa、GABAb和GABAc 受体在眼组织分布位置不同。在此基础上，拟通过研究GABAa、GABAb 和GABAc 受体激动剂和拮抗剂对豚鼠实验性近视眼屈光状态、视网膜GABA 含量、视网膜色素上皮(RPE)Ca2+和Cl-离子浓度及巩膜细胞外基质的影响，检测GABA 受体在眼组织表达，了解GABA 信号通路调控近视的作用部位和机制；通过研究GABA 类药物对体外培养RPECa2+和Cl-离子浓度及巩膜细胞外基质合成的影响，检测 GABA 受体在细胞中表达，明确RPE 和巩膜细胞是否为GABA 类药物直接作用的靶点。通过研究，明确视网膜、RPE 和巩膜在GABA 信号通路调控近视中的作用，阐明GABA 受体拮抗剂抑制近视的作用靶点和机制，为研制新型抗近视药物.提供新思路。