MOLECULAR MECHIANISM OF RETINAL GANGLION CELL APOTPTOSIS ANDEXPERIMENTAL GENE THERAPRYTO PREVENT THE CELL DEATH

视网膜神经节细胞凋亡的分子机制及预防细胞死亡的实验基因治疗

• 批准号: 10470361
• 负责人: YOSHIMURA Nagahisa
• 金额: $ 8.26万
• 依托单位: SHINSHU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470361/
• 关键词: RETINAL GANGLION CELLS; CELL DEATH; NEUROPROTECTION; CASPASE; C-JUN; BDNF; caspase; c-jun; NOS; 細胞神経節細胞; Caspase; C-Jun

(1) Research on rat retinal cell death following ischemia-reperfusionWE have shown that caspase-3 plays an important role in the inner retina, whereas caspase-1 was more important in the outer retina.Horizontal cells that express p16INK4 did not show apoptotic features but were necrotic but amacrine cells that do not express the gene were apoptotic.Reactive oxygen species played an important role in retinal ischemia-reperfusion injury.(2) Research on retinal ganglion cell apoptosisRetinal ganglion cells dying by apoptosis expressed c-jun and such cell also expressed caspase-2. Caspases-1 and -3 were not expressed dying retinal ganlion cells. BDNF treatment decreased the number of apoptotic cells but expression of c-jun was not different from without the treatment. Caspase-2 expression was decreased by the treatment.(3) Experimental gene therapy for RCS ratsTreatment of RCS rats with AAV-Bcl-xL was effective to reduce the visual cell damage found in the RCS rats.

(1)大鼠视网膜缺血再灌注后细胞死亡的研究表明，caspase-3在视网膜内层起重要作用，而caspase-1在视网膜外层起更重要的作用，表达p16 INK 4的水平细胞不显示凋亡特征，但发生坏死，而不表达该基因的无长突细胞发生凋亡，活性氧在视网膜缺血再灌注损伤中起重要作用。(2)视网膜神经节细胞凋亡的研究凋亡的视网膜神经节细胞表达c-jun，这种细胞也表达caspase-2。凋亡的视网膜神经节细胞不表达Caspase-1和Caspase-3。BDNF处理可减少凋亡细胞的数量，但c-jun的表达与未处理组无明显差异。Caspase-2表达降低。(3)RCS大鼠的实验性基因治疗用AAV-Bcl-xL治疗RCS大鼠可有效减轻RCS大鼠中发现的视觉细胞损伤。

项目成果

Shibuki H,Katai N,Kuroiwa S,Kurokawa T,Yodoi J,and Yoshimura N.: "Protective effect of adult T cell leukemia-derived factor on retinal ischemia-reperfusion injury in the rat."Invest Ophthalmol Vis Sci.. 39. 1470-1477 (1998)

Shibuki H、Katai N、Kuroiwa S、Kurokawa T、Yodoi J 和 Yoshimura N.：“成人 T 细胞白血病衍生因子对大鼠视网膜缺血再灌注损伤的保护作用。”Invest Ophasemol Vis Sci.. 39。

Shibuki H,Katai N,Yodoi J,Uchida K,and Yoshimura N.: "Lipid peoxidation and peroxynitrite in retinal ischema-reperfusion injury."Invest Ophthalmol Vis Sci. 41. 3607-3614 (2000)

Shibuki H、Katai N、Yodoi J、Uchida K 和 Yoshimura N.：“视网膜缺血再灌注损伤中的脂质过氧化和过氧亚硝酸盐。”Invest Ophasemol Vis Sci。

Kuroiwa S, Yoshimura N et al: "Apoptosis and necrisis in retinal ischemic reperfusion injury"Invest Ophthalmol Vis Sci. 40. 528-533 (1999)

Kuroiwa S、Yoshimura N 等人：“视网膜缺血再灌注损伤中的细胞凋亡和坏死”Invest Ophasemol Vis Sci。

Kuroiwa S,Katai N,Shibuki H,Yoshimura N. et al.: "Expression of cell cycle-related genes in dying cells following retinal ischemic injury in the rat."Invest Ophthalmol Vis Sci.. 39. 610-617 (1998)

Kuroiwa S,Katai N,Shibuki H,Yoshimura N.等人：“大鼠视网膜缺血性损伤后死亡细胞中细胞周期相关基因的表达。”Invest Ophasemol Vis Sci.. 39. 610-617 (1998)

Katai N, Kikuchi T, Shibuki H, Kuroiwa S.Arai J, Kurokawa T, and Yoshimura N.: "Caspase-like proteases activated in apoptotic photoreceptors of Royal College of Surgeons rat."Invest Ophthalmol Vis Sci.. 40. 1802-1807 (1999)

Katai N、Kikuchi T、Shibuki H、Kuroiwa S.Arai J、Kurokawa T 和 Yoshimura N.：“皇家外科学院大鼠凋亡光感受器中激活的半胱天冬酶样蛋白酶。”Invest Ophasemol Vis Sci.. 40. 1802-