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Dysregulation of trophic factors contributes to diabetic retinopathy in the Ins2Akita mouse.
Experimental Eye Research ( IF 3.4 ) Pub Date : 2020-04-04 , DOI: 10.1016/j.exer.2020.108027
Rute S Araújo 1 , Maria S Silva 2 , Daniela F Santos 3 , Gabriela A Silva 4
Affiliation  

Diabetic retinopathy (DR) is considered as a diabetes-related complication that can lead to severe visual impairments. By 2030, it is expected that 1 in 5 adults will suffer from the disease. Suitable animal models for chronic DR are essential for a better understanding of the pathophysiology and to further develop new treatments. The Ins2Akita mouse is a type 1 diabetes model that shows signs of both early and late stages of DR, including pericyte loss, increased vascular permeability, increased acellular capillaries and neovascularization. To further characterize DR in the Ins2Akita mouse model, we have evaluated the protein levels of the angiogenesis inducers vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) and the angiogenesis inhibitor pigment epithelium-derived factor (PEDF). Additionally, we have analyzed the protein expression profile of the glial markers ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) as well as of the chemokine monocyte chemoattractant protein 1 (MCP-1). In this study we demonstrate that, with disease progression, there is the development of an inflammatory response and an unbalanced expression of pro- and antiangiogenic factors in the neural retina and in the retinal pigment epithelium (RPE) of Ins2Akita mice. Therefore, our data provide support for the diabetic retinopathy features detected in the Ins2Akita retina, reflecting what is observed in the human pathology.

中文翻译:

营养因子的失调有助于Ins2Akita小鼠的糖尿病性视网膜病变。

糖尿病性视网膜病(DR)被认为是与糖尿病相关的并发症,可导致严重的视力障碍。到2030年,预计将有五分之一的成年人患有该疾病。合适的慢性DR动物模型对于更好地了解病理生理学和进一步开发新疗法至关重要。Ins2Akita小鼠是1型糖尿病模型,其显示DR早期和晚期的迹象,包括周细胞丢失,血管通透性增加,无细胞毛细血管增多和新血管形成。为了在Ins2Akita小鼠模型中进一步表征DR,我们评估了血管生成诱导剂血管内皮生长因子(VEGF)和胎盘生长因子(PlGF)以及血管生成抑制剂色素上皮衍生因子(PEDF)的蛋白水平。另外,我们已经分析了神经胶质标记离子化钙结合衔接分子1(Iba1)和神经胶质原纤维酸性蛋白(GFAP)以及趋化因子单核细胞趋化蛋白1(MCP-1)的蛋白表达谱。在这项研究中,我们证明,随着疾病的发展,Ins2Akita小鼠的神经视网膜和视网膜色素上皮(RPE)中出现炎症反应以及促血管生成因子和抗血管生成因子的表达不平衡。因此,我们的数据为在Ins2Akita视网膜中检测到的糖尿病性视网膜病变特征提供了支持,反映了在人类病理学中观察到的情况。
更新日期:2020-04-06
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