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玻璃体内注射粒细胞集落刺激因子对兔眼的视网膜毒性

Retinal Toxicity of Intravitreal Granulocyte Colony-Stimulating Factor in Rabbit Eyes.

作者信息

Falavarjani Khalil Ghasemi, Habibi Abbas, Pourhabibi Arash, Hosseini Seyed Bagher, Modarres Mehdi, Parvaresh Mohammad Mehdi, Shahriari-Ahmadi Ali

机构信息

a Department of Ophthalmology, Eye Research Center , Rassoul Akram Hospital, Iran University of Medical Sciences , Tehran , Iran.

b Central Eye Bank of Iran , Tehran , Iran.

出版信息

Curr Eye Res. 2017 Apr;42(4):636-639. doi: 10.1080/02713683.2016.1227447. Epub 2016 Oct 12.

Abstract

PURPOSE

Granulocyte colony-stimulating factor (G-CSF) has potential ocular neuroprotective effects. The aim of this study was to evaluate the retinal toxicity of intravitreal G-CSF in rabbit eye.

METHODS

Eight New Zealand albino rabbits, weighing between 2 and 3 kg, were selected for this study. The initial concentration of G-CSF (300 µg/0.5 ml) was titrated to obtain different concentrations of 45 μg, 30 μg, 15 μg, and 7.5 μg in 0.1 ml. Each concentration was injected into two rabbit eyes. For each dose, dextrose was injected in one contralateral eye and the other fellow eye remained non-injected. Electroretinographic (ERG) testing was performed before and 4 weeks after injections. The rabbits were euthanized and the eyes were enucleated 4 weeks after injections and examined using light microscopy and immunohistochemistry.

RESULTS

One rabbit with the injected dosage of 7.5 µg died at the first post-injection day. No sign of intraocular toxicity was found in clinical examination in other rabbits. A significant decrease in at least one of the a- or b-wave measurements of scotopic or photopic responses was found in 45 µg, 15 µg, and 7.5 µg injected eyes. Eyes with an intravitreal injection dosage of 30 µg G-CSF did not have significant changes compared to the baseline values. Histologic and immunohistochemistric studies were unremarkable for pathologic changes in all injected eyes.

CONCLUSION

While histologic and immunohistochemistric examinations revealed no toxicity in all G-CSF-injected eyes, significant ERG changes were observed in all doses except for the dose of 30 µg/0.1 ml.

摘要

目的

粒细胞集落刺激因子(G-CSF)具有潜在的眼部神经保护作用。本研究旨在评估玻璃体内注射G-CSF对兔眼的视网膜毒性。

方法

选取8只体重在2至3千克之间的新西兰白化兔进行本研究。将G-CSF的初始浓度(300μg/0.5ml)进行滴定,以在0.1ml中获得45μg、30μg、15μg和7.5μg的不同浓度。每个浓度分别注射到两只兔眼中。对于每一个剂量,在对侧的一只眼中注射葡萄糖,另一只眼不注射。在注射前和注射后4周进行视网膜电图(ERG)测试。在注射后4周对兔子实施安乐死并摘除眼球,然后使用光学显微镜和免疫组织化学进行检查。

结果

一只注射剂量为7.5μg的兔子在注射后的第一天死亡。在其他兔子的临床检查中未发现眼内毒性迹象。在注射了45μg、15μg和7.5μg的眼中,暗视或明视反应的a波或b波测量值至少有一项显著下降。与基线值相比,玻璃体内注射30μg G-CSF的眼睛没有显著变化。组织学和免疫组织化学研究显示,所有注射眼均未出现明显的病理变化。

结论

虽然组织学和免疫组织化学检查显示所有注射G-CSF的眼睛均无毒性,但除了30μg/0.1ml剂量外,在所有剂量下均观察到了显著的ERG变化。

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