Vps35 haploinsufficiency results in degenerative-like deficit in mouse retinal ganglion neurons and impairment of optic nerve injury-induced gliosis.
Vps35 haploinsufficiency results in degenerative-like deficit in mouse retinal ganglion neurons and impairment of optic nerve injury-induced gliosis.
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DOI：
10.1186/1756-6606-7-10
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发表时间：
2014-02-11
期刊：
影响因子：
3.6
通讯作者：
Xiong WC
中科院分区：
文献类型：
--
作者：
Liu W;Tang FL;Erion J;Xiao H;Ye J;Xiong WC
VPS 35（vacuolar protein sorting 35）是选择性地促进跨膜蛋白的内体至高尔基体回收的逆转录酶的主要组分。逆转录酶功能障碍是帕金森病（PD）和阿尔茨海默病（AD）这两种神经退行性疾病发病的危险因素。然而，VPS 35/retromer在视网膜中的功能或VPS 35缺陷对视网膜神经退行性疾病的贡献尚未研究。在这里，我们提供了VPS 35在小鼠视网膜神经节细胞（RGC）的存活和再生中的作用的证据。VPS 35在发育中的小鼠RGC中选择性表达。来自年轻成人Vps 35杂合子（Vps 35 +/m）的RGC显示退化样特征，例如营养不良的树突、减少的轴突纤维和增加的TUNEL标记的RGC。此外，视神经中的神经胶质增生在新生小鼠中短暂升高，但在老年Vps 35 +/m小鼠中降低。在Vps 35 +/m小鼠中，视神经损伤诱导的神经胶质增生也减弱。这些结果表明，Vps 35是小鼠RGC存活和再生所必需的，并且Vps 35缺陷可能有助于视网膜神经节神经变性的发病机制，这是导致许多视网膜变性疾病失明的关键病理学。
VPS35 (vacuolar protein sorting 35) is a major component of retromer that selectively promotes endosome-to-Golgi retrieval of transmembrane proteins. Dysfunction of retromer is a risk factor for the pathogenesis of Parkinson’s disease (PD) and Alzheimer’s disease (AD), both neuro-degeneration disorders. However, VPS35/retromer’s function in retina or the contribution of Vps35-deficiency to retinal neuro-degenerative disorders has not been investigated. Here we provide evidence for a role of VPS35 in mouse retinal ganglion cell (RGC) survival and regeneration. VPS35 is selectively expressed in developing mouse RGCs. RGCs from young adult Vps35 heterozygotes (Vps35+/m) show degenerative-like features, such as dystrophic dendrites, reduced axon fibers, and increased TUNEL labeled RGCs. Additionally, gliosis in the optic nerve is transiently elevated in neonatal, but reduced in aged Vps35+/m mice. Optic nerve injury-induced gliosis is also attenuated in Vps35+/m mice. These results suggest that Vps35 is necessary for mouse RGC survival and regeneration, and Vps35-deficiency may contribute to the pathogenesis of retinal ganglion neuro-degeneration, a critical pathology leading to the blindness of many retinal degenerative disorders.
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DOI：
10.1083/jcb.201207154
发表时间：
2013-03-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Xia WF;Tang FL;Xiong L;Xiong S;Jung JU;Lee DH;Li XS;Feng X;Mei L;Xiong WC
通讯作者：
Xiong WC
DOI：
10.1083/jcb.137.1.79
发表时间：
1997-04-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Seaman MN;Marcusson EG;Cereghino JL;Emr SD
通讯作者：
Emr SD
影响因子：
56.9
作者：
RAFF, MC
通讯作者：
RAFF, MC
影响因子：
2.4
作者：
Wang CL;Tang FL;Peng Y;Shen CY;Mei L;Xiong WC
通讯作者：
Xiong WC
影响因子：
9.8
作者：
Zimprich, Alexander;Benet-Pages, Anna;Strom, Tim M.
通讯作者：
Strom, Tim M.