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[半胱天冬酶3抑制剂Ac-DEVD-CHO对实验性近视视网膜细胞凋亡的治疗作用]

[The treatment of retinal apoptosis by Caspase 3 inhibitor Ac-DEVD-CHO in experimental myopia].

作者信息

Liu Shuang-zhen, Mao Jun-feng, Wen Dan, Tan Xing-ping, Fu Chun-yan

机构信息

Department of Ophthalmology, Xiangya Hospital, Central South University, Changsha 410008, China.

出版信息

Zhonghua Yan Ke Za Zhi. 2005 May;41(5):428-33.

PMID:15938808
Abstract

OBJECTIVE

To investigate the mechanism of retinal apoptosis in chick experimental myopia and the therapy of Caspase 3 inhibitor Ac-DEVD-CHO.

METHODS

Chick myopia was induced by lid-suture. After Ac-DEVD-CHO had been injected into vitreous, myopia was confirmed by optometry. Subsequently, chick eyeballs removed were measured its extro-dimensions, and the change of fundus were observed. Retinal apoptotic cells were determined by electron microscopy, TUNEL technique and flow cytometry. Retinal Caspase 3 proteins and its activities were measured by immunohistochemistry, flow cytometry and a colorimetric method using Ac-DEVD-pNA as a substrate.

RESULTS

Ocular diopters and extro-diameters in all sutured eyes remarkly increased in comparison with its control eyes at 12 weeks after lid-suture. Lacquer crack lesions were found in 41 of 90 sutured eyes (45.56%). Apoptotic cells were observed in retinal outer and inner nuclear layer of the sutured eyes, and its apoptotic rate was significantly more than in control eyes (P < 0.05). Moreover, the expression of retinal Caspase 3 proteins and its activities were increased. After Ac-DEVD-CHO was injected into vitreous, the decrease of retinal apoptotic rate, Caspase 3 proteins and its activities was found. The treated effect of Ac-DEVD-CHO was in a dose dependent manner.

CONCLUSIONS

Caspase 3 plays an important role in retinal apoptosis of chick myopia. Ac-DEVD-CHO can effectively ameliorate retinal apoptosis by blocked the effect of Caspase 3.

摘要

目的

探讨雏鸡实验性近视视网膜细胞凋亡机制及Caspase 3抑制剂Ac-DEVD-CHO的治疗作用。

方法

采用眼睑缝合诱导雏鸡近视。向玻璃体内注射Ac-DEVD-CHO后，通过验光确定近视形成。随后，测量摘除的雏鸡眼球的外部尺寸，并观察眼底变化。采用电子显微镜、TUNEL技术和流式细胞术检测视网膜凋亡细胞。采用免疫组织化学、流式细胞术和以Ac-DEVD-pNA为底物的比色法检测视网膜Caspase 3蛋白及其活性。

结果

与对照眼相比，所有缝合眼在眼睑缝合后12周时眼屈光度和眼球外径均显著增加。90只缝合眼中有41只（45.56%）出现漆裂纹病变。在缝合眼的视网膜外核层和内核层观察到凋亡细胞，其凋亡率显著高于对照眼（P<0.05）。此外，视网膜Caspase 3蛋白表达及其活性增加。向玻璃体内注射Ac-DEVD-CHO后，视网膜凋亡率、Caspase 3蛋白及其活性降低。Ac-DEVD-CHO的治疗效果呈剂量依赖性。

结论

Caspase 3在雏鸡近视视网膜细胞凋亡中起重要作用。Ac-DEVD-CHO可通过阻断Caspase 3的作用有效改善视网膜细胞凋亡。