Protein screening and analysis for the retina degeneration

视网膜变性的蛋白质筛选和分析

• 批准号: 16591756
• 负责人: MISHIMA Hiromu
• 金额: $ 2.24万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591756/
• 关键词: protemiomcs; chick embryo; retina; Wnt14; R28 cells; Caspase-3; neuroprotection; 家鶏胚; R28細胞; Caspase-3; 神経保護作用; マススペストロメトリー; 組み合わせプロテオミクス解析; 網膜神経節細胞; cell-sorting system; 3次元培養

Proteomics analysis was performed for the screening of proteins, related with retina survival, differentiation and regeneration Many proteins, including transcriptional factors, structural proteins, apoptosis factor, differentiation factors and novel proteins, were identified. Among of them, we focus on the Wnt14, one of the protein family for the differentiation, and the cell signaling of Wnt14 was analyzed. Immunohistochemistry shows that Wnt14 was endogeneously located in retinal ganglion cells of chick embryo retina. And, overexpressed Wnt14 inhibit cell death of R28 cells, rat retinal cell line, induced by glutamate neuronal toxity. Moreover, Wnt14 have the neuronal protective effect through the inhibition of activated caspase-3. apoptosis inducer.On the other hand, we also newly porteomics, using glaucoma model mouse retina, to find out the proteins associated with retinal survival factor in glaucoma. In result, the protein targets for glaucomatous retina degeneration were identified. PDGFR, one of the identified protein, was located in retinal ganglion cells on mouse retina, and PDGF-AA, specific ligand for PDGFR, have the neuro protective effect on the cell death of RGC-5, rat retina ganglion cell line, induced by glutamate. Finally, we succeeded in finding out newly neurotrophic proteins for retina.In addition, we check the genomic DNA of glaucoma patients, and we found polymorphism of TNF-alpha, Angiotensin-II receptor, Endothelin A receptor were associated with glaucoma. Otherwise, ApoE polymorphism, seen in Alzheimer disease, have no relation with glaucoma

利用蛋白质组学技术筛选与视网膜存活、分化和再生相关的蛋白质，鉴定出转录因子、结构蛋白、凋亡因子、分化因子和新的蛋白质。其中，我们重点研究了分化蛋白家族中的Wnt 14，并分析了Wnt 14的细胞信号传导。免疫组化显示Wnt 14内源性定位于鸡胚视网膜神经节细胞。过量表达Wnt 14可抑制谷氨酸神经毒性诱导的大鼠视网膜细胞系R28细胞死亡。此外，Wnt 14还通过抑制活化的caspase-3发挥神经元保护作用。另一方面，我们也采用了新的门体学方法，以青光眼模型小鼠视网膜为研究对象，寻找与青光眼视网膜存活因子相关的蛋白质。结果，确定了青光眼视网膜变性的蛋白质靶点。PDGFR蛋白定位于小鼠视网膜神经节细胞，其特异性配体PDGF-AA对谷氨酸诱导的大鼠视网膜神经节细胞系RGC-5细胞死亡具有神经保护作用。此外，我们还对青光眼患者的基因组DNA进行了检测，发现TNF-α、血管紧张素Ⅱ受体、内皮素A受体的多态性与青光眼的发病相关。另外，Alzheimer病中的ApoE基因多态性与青光眼无关

项目成果

Neuroprotective effects of erythropoietin on glutamate and nitric oxide toxicity in primary cultured retinal ganglion cells

• DOI: 10.1016/j.brainres.2005.05.037
• 发表时间: 2005-07
• 期刊: Brain Research
• 影响因子: 2.9
• 作者: Makiko Yamasaki;H. Mishima;H. Yamashita;K. Kashiwagi;K. Murata;A. Minamoto;T. Inaba

Genetic polymorphisms in the angiotensin II receptor gene and their association with open-angle glaucoma in a Japanese population

• DOI: 10.1167/iovs.04-1100
• 发表时间: 2005-06-01
• 期刊: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
• 影响因子: 4.4
• 作者: Hashizume, K;Mashima, Y;Miyaki, K
• 通讯作者: Miyaki, K

Association between glaucoma and gene polymorphism of endothelin type A receptor.

青光眼与内皮素A型受体基因多态性的关联。

• 发表时间: 2005
• 期刊: Molecular Vision 11
• 作者: Yasuaki Harabuchi;et.al;原渕保明;Takeo Fukuchi;Takeo Fukuchi;Haruki Abe;Haruki Abe;澤田 英子;阿部春樹;白柏 基宏;福地 健郎;Fumie Hayama;Takeo Fukuchi;Motohiro Shirakashi;Takeo Fukuchi;Hideko Sawada;Haruki Abe;Haruki Abe;Haruki Abe;Haruki Abe;阿部春樹;阿部春樹;白柏 基宏;澤田 英子;Tetsuya Togano;Takeo Fukuchi;Masaaki Seki;Kiyoshi Yaoeda;Motohiro Shirakashi;Takeo Fukuchi;K.Hashimoto;Haruki Abe;Masaaki Seki;福地 健郎;阿部 春樹;阿部 春樹;白柏 基宏;原 浩昭;白柏 基宏;上田 潤;上田 潤;福地 健郎;福島 淳志;白柏 基宏;葉山 文恵;福地 健郎;八百枝 潔;Tetsuya Togano;Takeo Fukuchi;Masaaki Seki;Kiyoshi Yaoeda;Motohiro Shirakashi;Takeo Fukuchi
• 通讯作者: Takeo Fukuchi

High frequency of open-angle glaucoma in Japanese patients with Alzheimer's disease

• DOI: 10.1016/j.jns.2006.02.009
• 发表时间: 2006-07-15
• 期刊: JOURNAL OF THE NEUROLOGICAL SCIENCES
• 影响因子: 4.4
• 作者: Tamura, Hiroki;Kawakami, Hideshi;Mishima, Hiromu K.
• 通讯作者: Mishima, Hiromu K.

Statistical evaluation of the diagnostic accuracy of methods used to determine the progression of visual field defects in glaucoma

• DOI: 10.1016/j.ophtha.2004.06.025
• 发表时间: 2004-11-01
• 期刊: OPHTHALMOLOGY
• 影响因子: 13.7
• 作者: Mayama, C;Araie, M;Ohashi, Y
• 通讯作者: Ohashi, Y