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钴中毒可诱导小鼠发生视网膜病变和视神经病变。

Cobalt Toxicity Induces Retinopathy and Optic Neuropathy in Mice.

机构信息

The Krieger Eye Research Laboratory, Bruce and Ruth Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel.

https://orcid.org/0009-0006-0675-5641.

出版信息

Invest Ophthalmol Vis Sci. 2024 Nov 4;65(13):59. doi: 10.1167/iovs.65.13.59.

Abstract

PURPOSE

To explore the effect of cobalt toxicity on vision.

METHODS

A total of 103 wild-type (WT) mice were injected with cobalt chloride by two routes in different concentrations: single intravenous (IV) high or low doses (total, n = 43); or daily repeated intraperitoneal (IP) high (three days) or low (28 days, 56 days) dose, and low-dose cobalt with added minocycline (56 days) (total, n = 60); 10 WT mice served as a control group. An additional group of 17 immunodeficient NOD scid gamma (NSG) mice were injected IV or IP with cobalt, and 10 NSG mice served as control. Cobalt levels were measured in blood, urine, and tears by particle-induced X-ray emission (PIXE). Macroscopic, immunohistochemical, electroretinography (ERG), and molecular studies were done.

RESULTS

PIXE revealed cobalt elimination from the blood by two hours, with increased levels in urine but under the detection limit in tears. In the retina, ERG recordings showed decreased b-wave amplitude. Apoptosis mainly involved the inner retina, with inner retinal inflammatory reaction in both WT and less in the NSG mice. In the optic nerves, an increased microglial and astrocytic activation was noted.

CONCLUSIONS

This study demonstrated functional visual impairment with extensive inflammatory reaction secondary to cobalt toxicity in mice.

摘要

目的

探索钴毒性对视力的影响。

方法

共将 103 只野生型(WT)小鼠通过两种不同浓度的钴氯化物途径进行注射:单次静脉(IV)高或低剂量(共 43 只);或每日重复腹腔内(IP)高剂量(3 天)或低剂量(28 天、56 天),以及低剂量钴加米诺环素(56 天)(共 60 只);10 只 WT 小鼠作为对照组。另外一组 17 只免疫缺陷 NOD scid gamma(NSG)小鼠经 IV 或 IP 注射钴,10 只 NSG 小鼠作为对照组。采用质子诱导 X 射线发射(PIXE)法测量血液、尿液和泪液中的钴含量。进行宏观、免疫组织化学、视网膜电图(ERG)和分子研究。

结果

PIXE 显示钴在两小时内从血液中排出,尿液中钴含量增加,但在泪液中低于检测限。在视网膜中,ERG 记录显示 b 波振幅降低。凋亡主要涉及内视网膜,WT 小鼠的内视网膜炎症反应较 NSG 小鼠少。在视神经中,观察到小胶质细胞和星形胶质细胞的激活增加。

结论

本研究表明钴毒性在小鼠中导致功能性视力损害和广泛的炎症反应。

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