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非肥胖型糖尿病小鼠眼内致炎细胞因子:模拟糖尿病性视网膜病变的特征。

Intravitreal pro-inflammatory cytokines in non-obese diabetic mice: Modelling signs of diabetic retinopathy.

机构信息

Buchanan Ocular Therapeutics Unit, Department of Ophthalmology and the New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand.

Department of Ophthalmology and the New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand.

出版信息

PLoS One. 2018 Aug 22;13(8):e0202156. doi: 10.1371/journal.pone.0202156. eCollection 2018.

Abstract

Diabetic retinopathy is a vascular disease of the retina characterised by hyperglycaemic and inflammatory processes. Most animal models of diabetic retinopathy are hyperglycaemia-only models that do not account for the significant role that inflammation plays in the development of the disease. In the present study, we present data on the establishment of a new animal model of diabetic retinopathy that incorporates both hyperglycaemia and inflammation. We hypothesized that inflammation may trigger and worsen the development of diabetic retinopathy in a hyperglycaemic environment. Pro-inflammatory cytokines, IL-1β and TNF-α, were therefore injected into the vitreous of non-obese diabetic (NOD) mice. CD1 mice were used as same genetic background controls. Fundus and optical coherence tomography images were obtained before (day 0) as well as on days 2 and 7 after intravitreal cytokine injection to assess vessel dilation and beading, retinal and vitreous hyper-reflective foci and retinal thickness. Astrogliosis and microgliosis were assessed using immunohistochemistry. Results showed that intravitreal cytokines induced vessel dilation, beading, severe vitreous hyper-reflective foci, retinal oedema, increased astrogliosis and microglia upregulation in diabetic NOD mice. Intravitreal injection of inflammatory cytokines into the eyes of diabetic mice therefore appears to provide a new model of diabetic retinopathy that could be used for the study of disease progression and treatment strategies.

摘要

糖尿病性视网膜病变是一种以高血糖和炎症过程为特征的视网膜血管疾病。大多数糖尿病性视网膜病变的动物模型都是高血糖模型,不能解释炎症在疾病发展中的重要作用。在本研究中,我们提供了关于建立一种新的糖尿病性视网膜病变动物模型的资料,该模型结合了高血糖和炎症。我们假设炎症可能在高血糖环境中引发和加重糖尿病性视网膜病变的发展。因此,将促炎细胞因子 IL-1β和 TNF-α 注射到非肥胖型糖尿病(NOD)小鼠的玻璃体中。CD1 小鼠被用作相同遗传背景的对照。在玻璃体腔注射细胞因子前(第 0 天)以及注射后第 2 天和第 7 天,获取眼底和光学相干断层扫描图像,以评估血管扩张和珠状形成、视网膜和玻璃体高反射焦点以及视网膜厚度。通过免疫组织化学评估星形胶质细胞和小胶质细胞的激活。结果表明,玻璃体腔内细胞因子诱导糖尿病 NOD 小鼠血管扩张、珠状形成、严重玻璃体高反射焦点、视网膜水肿、星形胶质细胞和小胶质细胞上调。因此,向糖尿病小鼠的眼睛内注射炎症细胞因子似乎提供了一种新的糖尿病性视网膜病变模型,可用于研究疾病进展和治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b904/6105000/3bc04d2cbb7b/pone.0202156.g001.jpg

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