Monocyte activation in patients with age-related macular degeneration - A biomarker of risk for choroidal neovascularization?
Monocyte activation in patients with age-related macular degeneration - A biomarker of risk for choroidal neovascularization?
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DOI：
10.1001/archopht.122.7.1013
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发表时间：
2004-07-01
影响因子：
--
通讯作者：
Csaky, KG
中科院分区：
文献类型：
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作者：
Cousins, SW;Espinosa-Heidmann, DG;Csaky, KG
目的：评估年龄相关性黄斑变性（AMD）患者的巨噬细胞功能的激活状态，通过定量的促炎和血管生成因子肿瘤坏死因子α（TNF-α）的生产，并通过其表达与干，湿AMD.Methods：循环单核细胞从AMD患者或年龄匹配的对照组的血液中获得的梯度离心。然后分析单核细胞响应于视网膜色素上皮衍生的滤过泡和细胞因子或TNF-α从培养的巨噬细胞释放的TNF-α。结果：在从对照组和AMD患者获得的人单核细胞中，TNF-α由新鲜分离的单核细胞表达，并且在用视网膜色素上皮衍生的滤过泡刺激后由培养物中的巨噬细胞产生。然而，在不同患者中观察到TNF-α表达的广泛变异性。表达最大量的TNF-α的单核细胞的患者表现出较高的患病率脉络膜新生vascularization.Conclusions：控制和AMD患者的循环单核细胞的激活状态（定义为TNF-α表达）的变化。部分活跃的单核细胞，定义为高TNF-α表达，可能是一种生物标志物，以确定患者的风险形成脉络膜新生血管。临床相关性：早期诊断测试可能被证明是有用的，以检测那些患者谁将进展到更严重的并发症的疾病。
Objective: To evaluate the activation state of macrophage function in patients with age-related macular degeneration (AMD) by quantifying the production of the proinflammatory and angiogenic factor tumor necrosis factor alpha (TNF-alpha) and by correlating its expression with dry and wet AMD.Methods: Circulating monocytes were obtained from the blood of patients with AMD or age-matched control subjects by gradient centrifugation. The monocytes were then analyzed for either TNF-alpha release from cultured macrophages in response to retinal pigment epithelium-derived blebs and cytokines or TNF-alpha. messenger RNA content by reverse transcriptase-polymerase chain reaction.Results: In human monocytes obtained from controls and AMD patients, TNF-alpha was expressed by freshly isolated monocytes and produced by macrophages in culture after stimulation with retinal pigment epithelium-derived blebs. However, wide variability in TNF-alpha expression was observed among different patients. Patients with monocytes that expressed the greatest amount of TNF-alpha demonstrated higher prevalence of choroidal neovascularization.Conclusions: Both controls and AMD patients vary in the activation state (defined as TNF-alpha expression) of circulating monocytes. Partially active monocytes, defined as high TNF-alpha expression, may be a biomarker to identify patients at risk for formation of choroidal neovascularization.Clinical Relevance: Early diagnostic testing may prove useful to detect those patients who will progress to the more severe complications of the disease.