Do Beta 2-Glycoprotein I Disulfide Bonds Protect the Human Retina in the Setting of Age-Related Macular Degeneration?
Do Beta 2-Glycoprotein I Disulfide Bonds Protect the Human Retina in the Setting of Age-Related Macular Degeneration?
复制标题
DOI：
10.1089/ars.2014.6052
复制
发表时间：
2016-01-01
影响因子：
6.6
通讯作者：
Giannakopoulos, Bill
中科院分区：
文献类型：
--
作者：
Qi, Miao;Abdelatti, Mahmoud;Giannakopoulos, Bill
年龄相关性黄斑变性 (AMD) 影响负责高分辨率视力的视网膜区域。它是老年人失明的主要原因。这是第一项研究，检查早期和晚期 AMD 患者血浆中氧化还原修饰、基于半胱氨酸、翻译后形式的 β2-糖蛋白 I (2GPI) 与对照组的关系。还进行了探索，以评估 2GPI 的游离硫醇形式与氧化二硫化物形式在过氧化氢 (H2O2) 介导的永生化人视网膜色素上皮 (RPE) 细胞系的细胞死亡的情况下是否具有不同的功能特性。我们在 AMD 患者的视网膜和脉络膜中展示了 2GPI。游离硫醇 2GPI 可保护永生化人 RPE 细胞系免受 H2O2 诱导的细胞死亡，而氧化形式的 2GPI 和游离硫醇牛血清白蛋白则没有保护作用。与早期 AMD 和健康对照相比，晚期 AMD 患者的游离硫醇 2GPI 水平显着降低。我们的观察结果得出这样的假设：游离硫醇 2GPI 可以在 AMD 早期保护 RPE 细胞免受氧化应激损伤。
Age-related macular degeneration (AMD) affects the region of the retina that is responsible for high-resolution vision. It is a major cause of blindness in the aging population. This is the first study that examines the association of redox-modified, cysteine-based, post-translational forms of beta 2-glycoprotein I (2GPI) in the plasma of individuals with early and late stages of patients with AMD compared with controls. Exploration is also undertaken to assess whether the free thiol form of 2GPI versus the oxidized disulfide form have distinct functional properties in the setting of hydrogen peroxide (H2O2)-mediated cell death of an immortalized human retinal pigment epithelium (RPE) cell line. We demonstrate 2GPI in the retina and choroid of patients with AMD. Free thiol 2GPI is shown to protect the immortalized human RPE cell line against H2O2-induced cell death, whereas the oxidized form of 2GPI and free thiol bovine serum albumin were not protective. Free thiol 2GPI levels were significantly decreased in patients with late AMD compared with early AMD and healthy controls. Our observations lead to the hypothesis that free thiol 2GPI may protect against oxidative stress injury to RPE cells in the early stages of AMD.