Chronic hyperglycemia alters retinal astrocyte microstructure and uptake of cholera toxin B in a murine model of diabetes.

IF 4.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Joseph M Holden, Olivia L Bossardet, Ghazi Bou Ghanem, David J Calkins, Lauren K Wareham
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Abstract

Astrocytes are the principle glial cells of the central nervous system and play an active role in maintaining proper metabolism in surrounding neurons. Because of their involvement in metabolic control, it is likely that their physiology changes in response to metabolic diseases such as diabetes and associated diabetic retinopathy. Here, we investigated whether microstructural changes in astrocyte morphology occur during the early stages of chronic hyperglycemia that may be indicative of early pathogenic programs. We used MORF3 mice in conjunction with streptozotocin-induced hyperglycemia to investigate the morphology of single retinal astrocytes at an early timepoint in diabetic disease. We report that astrocytes initiate a morphological remodeling program, which depends on both the glycemic background and the presence of intravitreal injury, to alter the amount of the neuronal-associated pad and bristle microstructural motifs. Additionally, hyperglycemia increases astrocyte uptake of cholera toxin B, possibly reflecting changes in glycolipid and glycoprotein biosynthesis. Chronic hyperglycemia coupled with intravitreal injection of cholera toxin B also causes extensive leukocyte infiltration into the retina. Our results have important clinical relevance as current therapies for diabetic retinopathy involve intravitreal injection of pharmaceuticals in individuals with often poorly controlled blood glucose levels.

在小鼠糖尿病模型中,慢性高血糖会改变视网膜星形胶质细胞的微结构和对霍乱毒素 B 的吸收。
星形胶质细胞是中枢神经系统的主要胶质细胞,在维持周围神经元的正常新陈代谢方面发挥着积极作用。由于星形胶质细胞参与代谢控制,它们的生理机能很可能会随着代谢性疾病(如糖尿病和相关的糖尿病视网膜病变)的发生而发生变化。在此,我们研究了星形胶质细胞形态的微观结构变化是否发生在慢性高血糖的早期阶段,而这种变化可能是早期致病程序的标志。我们利用 MORF3 小鼠和链脲佐菌素诱导的高血糖,研究了糖尿病病变早期单个视网膜星形胶质细胞的形态。我们报告说,星形胶质细胞启动了一个形态重塑程序,该程序取决于血糖背景和是否存在玻璃体内损伤,从而改变与神经元相关的垫和鬃毛微结构图案的数量。此外,高血糖会增加星形胶质细胞对霍乱毒素 B 的吸收,这可能反映了糖脂和糖蛋白生物合成的变化。长期高血糖加上静脉注射霍乱毒素 B 还会导致大量白细胞浸润视网膜。我们的研究结果具有重要的临床意义,因为目前治疗糖尿病视网膜病变的方法包括向血糖水平通常控制不佳的患者进行玻璃体内注射药物。
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来源期刊
Journal of Neurochemistry
Journal of Neurochemistry 医学-神经科学
CiteScore
9.30
自引率
2.10%
发文量
181
审稿时长
2.2 months
期刊介绍: Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.
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