Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia, Augusta University, Augusta, GA 30912, USA.
James and Jean Culver Vision Discovery Institute, MCG, Augusta University, Augusta, GA 30912, USA.
Biomolecules. 2020 Mar 3;10(3):393. doi: 10.3390/biom10030393.
Homocysteine (Hcy) is an amino acid that requires vitamins B and folic acid for its metabolism. Vitamins B and folic acid deficiencies lead to hyperhomocysteinemia (HHcy, elevated Hcy), which is linked to the development of diabetic retinopathy (DR), age-related macular degeneration (AMD), and Alzheimer's disease (AD). The goal of the current study was to explore inflammation as an underlying mechanism of HHcy-induced pathology in age related diseases such as AMD, DR, and AD. Mice with HHcy due to a lack of the enzyme cystathionine-β-synthase (CBS) and wild-type mice were evaluated for microglia activation and inflammatory markers using immuno-fluorescence (IF). Tissue lysates isolated from the brain hippocampal area from mice with HHcy were evaluated for inflammatory cytokines using the multiplex assay. Human retinal endothelial cells, retinal pigment epithelial cells, and monocyte cell lines treated with/without Hcy were evaluated for inflammatory cytokines and NFκB activation using the multiplex assay, western blot analysis, and IF. HHcy induced inflammatory responses in mouse brain, retina, cultured retinal, and microglial cells. NFκB was activated and cytokine array analysis showed marked increase in pro-inflammatory cytokines and downregulation of anti-inflammatory cytokines. Therefore, elimination of excess Hcy or reduction of inflammation is a promising intervention for mitigating damage associated with HHcy in aging diseases such as DR, AMD, and AD.
同型半胱氨酸（Hcy）是一种氨基酸，其代谢需要维生素 B 和叶酸。维生素 B 和叶酸缺乏会导致高同型半胱氨酸血症（HHcy，同型半胱氨酸升高），这与糖尿病视网膜病变（DR）、年龄相关性黄斑变性（AMD）和阿尔茨海默病（AD）的发展有关。本研究的目的是探讨炎症作为 HHcy 诱导 AMD、DR 和 AD 等与年龄相关疾病发病机制的潜在机制。使用免疫荧光（IF）评估缺乏胱硫醚-β-合酶（CBS）导致 HHcy 的小鼠和野生型小鼠的小胶质细胞活化和炎症标志物。使用多重分析评估 HHcy 小鼠脑海马区组织裂解物中的炎症细胞因子。使用多重分析、western blot 分析和 IF 评估用/不用 Hcy 处理的人视网膜内皮细胞、视网膜色素上皮细胞和单核细胞系中的炎症细胞因子和 NFκB 激活。HHcy 诱导了小鼠大脑、视网膜、培养的视网膜和小胶质细胞的炎症反应。NFκB 被激活，细胞因子阵列分析显示促炎细胞因子显著增加，抗炎细胞因子下调。因此，消除多余的 Hcy 或减轻炎症是减轻 DR、AMD 和 AD 等与年龄相关疾病中与 HHcy 相关的损伤的有前途的干预措施。
