Pathomechanisms of choroidal neovascularisation and oxidative stress

脉络膜新生血管与氧化应激的病理机制

• 批准号: 5375052
• 负责人: Professor Dr. Peter Wiedemann
• 金额: --
• 依托单位: Klinik und Poliklinik für Augenheilkunde
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2002
• 资助国家: 德国
• 起止时间: 2001-12-31 至 2005-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5375052?language=en
• 关键词: Pathomechanisms; choroidal; neovascularisation; oxidative; stress

Choroidal neovascularization (CNV) is a key process in exsudative age-related macular degeneration (AMD), the leading cause of blindness in the elderly of the western world. In CNV, new vessels originated from choroidal circulation invade through Bruch's membrane and spread out under the retinal pigment epithelium (RPE). Choroidal endothelial cells (CEC) are stimulated to migrate, proliferate, and invade surrounding tissues. Although the primary stimulus for the development of CNV is unknown, stimulation of CEC is probably related to altered RPE cell function. Oxidative stress caused by reactive oxygen species (ROS) has been implicated in several age-related disorders and is considered as an important mechanism involved in pathological alterations which may result in CNV. It has been suggested that AMD is accompanied by lack of antioxidants resulting in elevated oxidative stress. Results of a recent study (AREDS, age-related eye disease study) strongly suggest, that dietary supplementation of antioxidants and zinc can be beneficial for AMD patients in preventing progression to advanced AMD. CEC and RPE cells are discussed to be the most important cells involved in pathogenesis of AMD. We hypothesize that oxidative stress has direct and indirect effects on the CNV-related CEC and RPE cells, resulting in upregulated angiogenic processes. To corroborate this hypothesis the purpose of our study is to investigate the role of oxidative stress on processes involved in pathogenesis of CNV. In detail, we will focus our study on cellular effects of oxidative stress, as a consequence of direct exposure to oxidants, or mediated indirectly by release of RPE-associated soluble factors. We propose to study effects of oxidative stress on the expression of selected angiogenesis-related cytokines, chemokines, and matrix metalloproteinases and to determine CEC proliferation/viability, sprouting, migration, and tube formation under this condition. Also effects of oxidative stress on CEC and RPE cell coculture will be investigated.

脉络膜新生血管（CNV）是渗出性年龄相关性黄斑变性（AMD）的关键过程，AMD是西方世界老年人失明的主要原因。在CNV中，源自脉络膜循环的新血管穿过Bruch膜侵入并在视网膜色素上皮(RPE)下扩散。脉络膜内皮细胞（CEC）受到刺激而迁移、增殖并侵入周围组织。尽管 CNV 发展的主要刺激因素尚不清楚，但 CEC 的刺激可能与 RPE 细胞功能的改变有关。活性氧 (ROS) 引起的氧化应激与多种年龄相关疾病有关，并被认为是可能导致 CNV 的病理改变的重要机制。有人认为，AMD 伴随着抗氧化剂的缺乏，导致氧化应激升高。最近的一项研究（AREDS，与年龄相关的眼病研究）的结果强烈表明，饮食中补充抗氧化剂和锌可能有利于 AMD 患者预防进展为晚期 AMD。 CEC 和 RPE 细胞被认为是参与 AMD 发病机制的最重要的细胞。我们假设氧化应激对 CNV 相关的 CEC 和 RPE 细胞有直接和间接的影响，导致血管生成过程上调。为了证实这一假设，我们研究的目的是调查氧化应激在 CNV 发病机制中的作用。具体来说，我们将重点研究氧化应激对细胞的影响，氧化应激是直接暴露于氧化剂的结果，或通过 RPE 相关可溶性因子的释放间接介导。我们建议研究氧化应激对选定的血管生成相关细胞因子、趋化因子和基质金属蛋白酶表达的影响，并确定在此条件下 CEC 的增殖/活力、出芽、迁移和管形成。还将研究氧化应激对 CEC 和 RPE 细胞共培养的影响。