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重组促红细胞生成素玻璃体腔内注射对实验性视网膜脱离大鼠光感受器细胞保护的安全性及有效性研究。

Safety and efficacy of intravitreal injection of recombinant erythropoietin for protection of photoreceptor cells in a rat model of retinal detachment.

机构信息

Department of Ophthalmology, Clinical Medical School, Yangzhou University, Yangzhou, Jiangsu, China.

出版信息

Eye (Lond). 2012 Jan;26(1):144-52. doi: 10.1038/eye.2011.254. Epub 2011 Oct 21.

DOI:10.1038/eye.2011.254
PMID:22020175
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3259587/
Abstract

PURPOSE

To elucidate the safety and efficacy of exogenous erythropoietin (EPO) for the protection of photoreceptor cells in a rat model of retinal detachment (RD).

METHODS

Recombinant rat EPO (400 ng) was injected into the vitreous cavity of normal rats to observe the eye manifestations. Retinal function was assessed by flash electroretinograms. Histopathological examination of retinal tissue was performed at 14 days and 2 months after injection, respectively. To investigate the inhibitory effect of EPO on photoreceptor cell apoptosis in RD rats, 100, 200, or 400 ng EPO was injected into the vitreous cavity immediately after RD model establishment. Apoptosis of photoreceptor cells was determined at 3 days after injection. Caspase-3 activation was measured by western blot analysis and immunofluorescence, respectively, and the level of Bcl-X(L) expression was analyzed by western blot.

RESULTS

Intravitreal injection of EPO 400 ng into normal rats had no significant impact on retinal function, morphology, or structure. Apoptosis of retinal photoreceptor cells apparently increased after RD and was significantly reduced following EPO treatment. The thickness of the outer nuclear layer in the RD + 400 ng group was significantly thicker than that in other experimental RD groups both at 14 days and at 2 months after RD (P < 0.05). Western blot and immunofluorescence analyses showed decreased caspase-3 activation and increased Bcl-X(L) expression following EPO treatment.

CONCLUSION

Intravitreal injection of EPO 400 ng is safe, and EPO may suppress caspase-3 activation and enhance Bcl-X(L) expression, resulting in inhibition of apoptosis and protection of photoreceptor cells.

摘要

目的

阐明外源性促红细胞生成素(EPO)对视网膜脱离(RD)大鼠模型中光感受器细胞的保护作用及其安全性。

方法

将重组大鼠 EPO(400ng)注入正常大鼠的玻璃体腔,观察眼部表现。通过闪光视网膜电图评估视网膜功能。分别于注射后 14 天和 2 个月对视网膜组织进行组织病理学检查。为了研究 EPO 对 RD 大鼠光感受器细胞凋亡的抑制作用,在建立 RD 模型后立即向玻璃体腔注射 100、200 或 400ng 的 EPO。在注射后 3 天测定光感受器细胞的凋亡情况。通过 Western blot 分析和免疫荧光分别测定半胱氨酸天冬氨酸蛋白酶-3(caspase-3)的激活情况,并通过 Western blot 分析 Bcl-X(L)的表达水平。

结果

向正常大鼠玻璃体腔内注射 400ng 的 EPO 对视网膜功能、形态或结构没有明显影响。RD 后视网膜光感受器细胞凋亡明显增加,EPO 治疗后明显减少。RD+400ng 组在 RD 后 14 天和 2 个月时,外核层厚度均明显比其他实验性 RD 组厚(P<0.05)。Western blot 和免疫荧光分析显示,EPO 处理后 caspase-3 的激活减少,Bcl-X(L)的表达增加。

结论

玻璃体腔内注射 400ng 的 EPO 是安全的,EPO 可能通过抑制 caspase-3 的激活和增强 Bcl-X(L)的表达,抑制细胞凋亡,保护光感受器细胞。

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