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糖尿病性视网膜病变食蟹猴模型中视网膜星形胶质细胞和小胶质细胞的激活。

Retinal Astrocytes and Microglia Activation in Diabetic Retinopathy Rhesus Monkey Models.

机构信息

Laboratory of Animal Disease Model, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

出版信息

Curr Eye Res. 2022 Feb;47(2):297-303. doi: 10.1080/02713683.2021.1984535. Epub 2021 Oct 4.

Abstract

PURPOSE

To assess the retinal neurodegeneration in type-1 diabetes mellitus (T1DM) and type-2 diabetes mellitus (T2DM) rhesus monkeys, and to investigate whether alterations of glial cells occur in the early stage of diabetic retinopathy (DR).

MATERIALS AND METHODS

T1DM rhesus monkeys were established by daily intravenous injections of streptozotocin (STZ, 25 mg/kg body weight) in citrate buffer (pH 4.5) for 5 days, while T2DM rhesus monkeys were induced by feeding with high-fat diet. The period of DR in rhesus monkeys was evaluated by fundoscopy and optical coherence tomography (OCT). Afterward, the morphological changes of inner neurons and glial cells in the retina were detected by immunofluorescence (IF).

RESULTS

When compared with the control groups, no difference was observed in both T1DM and T2DM by fundus photographs, while slight exudation and effusion in the blood vessels of retina of rhesus monkeys were found by OCT in DM rhesus monkeys. In addition, the expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule (Iba1) were significantly increased in both T1DM ( < .01) and T2DM ( < .05) rhesus monkeys. Moreover, the positive expression of PKC-α, parvalbumin, and NeuN were significantly decreased, while the positive expression of calbindin showed no difference in T1DM group. However, only the expression cells of PKC-α were reduced in T2DM group when compared with that of the control group.

CONCLUSION

Astrocytes activation, reactive gliosis, and neurodegeneration were observed in both T1DM and T2DM rhesus monkey models at the early stage of DR.

摘要

目的

评估 1 型糖尿病(T1DM)和 2 型糖尿病(T2DM)恒河猴的视网膜神经退行性变,并研究胶质细胞的改变是否发生在糖尿病视网膜病变(DR)的早期。

材料和方法

T1DM 恒河猴通过每日静脉注射柠檬酸缓冲液(pH 4.5)中的链脲佐菌素(STZ,25mg/kg 体重)5 天来建立,而 T2DM 恒河猴通过高脂饮食诱导。通过眼底检查和光学相干断层扫描(OCT)评估恒河猴 DR 的病程。随后,通过免疫荧光(IF)检测视网膜内神经元和胶质细胞的形态变化。

结果

与对照组相比,眼底照片在 T1DM 和 T2DM 中均无差异,而 OCT 显示 DM 恒河猴视网膜血管有轻微渗出和积液。此外,GFAP 和 Iba1 的表达在 T1DM(<0.01)和 T2DM(<0.05)恒河猴中均显著增加。此外,PKC-α、副甲状腺球蛋白和 NeuN 的阳性表达明显减少,而 calbindin 的阳性表达在 T1DM 组中没有差异。然而,与对照组相比,只有 T2DM 组的 PKC-α 表达细胞减少。

结论

在 DR 的早期阶段,T1DM 和 T2DM 恒河猴模型中观察到星形胶质细胞激活、反应性神经胶质增生和神经退行性变。

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