酪氨酸磷酸酶蛋白σ受体（PTPσ）参与视皮层可塑性终止的机制研究

Amblyopia is the chief cause of the molocular vision disorder in adults. After the termination of the critical period, the impair by amblyopia can not be repaired. Recent studies have shown that the CSPGs from extracelluar matrix is the crucial molecular for the termination of visual plasticity. PTPσ as the receptor of CSPGs, plays the role of the inhibition of axon growth,which give some clues for the molecular mechnism of CSPGs. This study is to set animal models and experiment in vitro, eliminating the expression of PTPσ.By using culturing neurons from visual cortex, patch clamp and transmission electron microscope, we try to find the influence of PTPσ and its downstream molecules on synaptic plasticity. Clarification of the molecular mechanism of the inhibitory function of PTPσ will provide some evidence to find the new drugs which could reactivate the visual plasticity in adults and expand the time window for the treatment of amblyopia.

弱视是成人单眼视觉障碍的首要病因。可塑性关键期终止后，弱视导致的视功能损害无法恢复。近年来的研究显示细胞外间质硫酸软骨素蛋白多糖（chondroitin sulphate proteoglycans，CSPGs）是视皮层可塑性关键期终止的关键分子，与成年视皮层可塑性再激活关系密切。而新近研究发现酪氨酸磷酸酶蛋白受体σ（protein tyrosine phosphatase σ, PTPσ）为CSPGs发挥抑制轴突生长作用的受体，为研究CSPGs的分子机制提供了线索。本项目拟通过在体和离体实验，干扰视皮层神经元中PTPσ的表达，通过神经元体外培养、膜片钳、透射电镜等技术研究PTPσ 受体及下游信号通路对神经元突触可塑性的影响。阐明PTPσ促进视皮层可塑性终止的相关分子机制，为寻找新药再激活成年视皮层可塑性，扩大弱视治疗的时间窗提供理论依据。

弱视是成人单眼视觉障碍的首要病因。可塑性关键期终止后，弱视导致的视功能损害无法恢复。近年来的研究显示细胞外间质硫酸软骨素蛋白多糖（chondroitin sulphate proteoglycans，CSPGs）是视皮层可塑性关键期终止的关键分子，与成年视皮层可塑性再激活关系密切。而新近研究发现酪氨酸磷酸酶蛋白受体σ（protein tyrosine phosphatase σ, PTPσ）为CSPGs发挥抑制轴突生长作用的受体，为研究CSPGs的分子机制提供了线索。本项目拟通过在体和离体实验，干扰视皮层神经元中PTPσ的表达，通过神经元体外培养、膜片钳、透射电镜等技术研究PTPσ 受体及下游信号通路对神经元突触可塑性的影响。阐明PTPσ促进视皮层可塑性终止的相关分子机制，为寻找新药再激活成年视皮层可塑性，扩大弱视治疗的时间窗提供理论依据。