Gachon Institute of Pharmaceutical Science, Gachon University, Incheon, Republic of Korea.
MetiMedi Pharmaceuticals Co., Research Center, Incheon, Republic of Korea.
Life Sci. 2019 Sep 15;233:116727. doi: 10.1016/j.lfs.2019.116727. Epub 2019 Aug 2.
Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in elderly people. The pathogenesis of neovascular AMD is known but is closely related to inflammation and choroidal neovascularization (CNV). The aim of this study was to investigate the anti-inflammatory and anti-angiogenic effects of calcium on neovascular AMD.
Human retinal pigment epithelial cells (ARPE-19) were used to identify protein markers of inflammation induced by differentiated macrophages. Choroidal neovascularization (CNV) mouse model was established by rupturing the Bruch's membrane using laser photocoagulation in C57BL/6 mice. Mice were divided into the following groups: untreated control and calcium supplemented. The expression levels of toll-like receptor isotype (TLR) 4, nuclear factor kappa B (NF-κB), hypoxia-inducible factor-1α (Hif-1α), and vascular endothelial growth factor (VEGF) were investigated to check whether calcium supplementation results in suppression of inflammation and has an anti-angiogenic effect. CNV was evaluated by immunofluorescence staining on choroidal flat mounts.
The inflammation-induced expression of TLR4, NF-κB, and Hif-1α was decreased in ARPE-19 cells after calcium supplementation. Inhibition of the transcriptional activation of ARPE-19 cells by Hif-1α suppression resulted in decreased VEGF expression. In the laser-induced CNV mouse model, calcium supplementation inhibited inflammatory mediators and neovascularization in the retinal tissue.
Supplementation with calcium seems to constrain inveterate symptoms of neovascular AMD by inhibiting inflammation and angiogenesis in the laser-induced CNV mouse model.
年龄相关性黄斑变性（AMD）是导致老年人不可逆性失明的主要原因。新生血管性 AMD 的发病机制虽然已经明确，但与炎症和脉络膜新生血管化（CNV）密切相关。本研究旨在探讨钙对新生血管性 AMD 的抗炎和抗血管生成作用。
使用人视网膜色素上皮细胞（ARPE-19）鉴定由分化的巨噬细胞引起的炎症的蛋白标记物。通过在 C57BL/6 小鼠中用激光光凝破坏 Bruch 膜建立脉络膜新生血管（CNV）小鼠模型。将小鼠分为以下几组：未处理对照组和钙补充组。检测 Toll 样受体 4（TLR）4、核因子 kappa B（NF-κB）、缺氧诱导因子-1α（Hif-1α）和血管内皮生长因子（VEGF）的表达水平，以检查钙补充是否导致炎症抑制和具有抗血管生成作用。通过脉络膜平面铺片的免疫荧光染色评估 CNV。
钙补充后，ARPE-19 细胞中 TLR4、NF-κB 和 Hif-1α 的炎症诱导表达减少。Hif-1α 抑制抑制 ARPE-19 细胞的转录激活导致 VEGF 表达减少。在激光诱导的 CNV 小鼠模型中，钙补充抑制了视网膜组织中的炎症介质和新生血管形成。
钙补充似乎通过抑制激光诱导的 CNV 小鼠模型中的炎症和血管生成来限制新生血管性 AMD 的固有症状。
