氧化型低密度脂蛋白诱导的视网膜色素上皮细胞损伤通过外泌体和凋亡泡释放改变膜补体调节因子 CD46 和 CD59 的表达。

Oxidized low-density-lipoprotein-induced injury in retinal pigment epithelium alters expression of the membrane complement regulatory factors CD46 and CD59 through exosomal and apoptotic bleb release.

机构信息

Wilmer Eye Institute, Johns Hopkins School of Medicine, 400 N. Broadway, Smith Building, room 3015, 21287, Baltimore, MD, USA,

出版信息

Adv Exp Med Biol. 2014;801:259-65. doi: 10.1007/978-1-4614-3209-8_33.

DOI:10.1007/978-1-4614-3209-8_33

PMID:24664706

Abstract

Genetic and immunohistochemical studies have identified the alternative complement pathway as an important component of age-related macular degeneration (AMD). The objective of this chapter is to review the impact of complement regulators on complement activation in the macula as it relates to AMD. Our laboratory and other investigators have identified CD46 and CD59 as important retinal pigment epithelium (RPE) cell membrane complement regulators, which are decreased in AMD. Using oxidized low-density lipoproteins (oxLDLs), which are found in Bruch's membrane in AMD, we found that CD46 and CD59 were decreased in RPE cells in part, by their release in exosomes and apoptotic particles. The release of complement regulators could potentially impair complement regulation on RPE cells and contribute to lesion formation in the outer retina and Bruch's membrane during the development of AMD.

摘要

遗传和免疫组织化学研究已经确定了替代补体途径是年龄相关性黄斑变性 (AMD) 的重要组成部分。本章的目的是回顾补体调节剂对与 AMD 相关的黄斑区补体激活的影响。我们实验室和其他研究人员已经确定 CD46 和 CD59 是重要的视网膜色素上皮 (RPE) 细胞膜补体调节剂，它们在 AMD 中减少。我们使用在 AMD 中存在于布鲁赫膜中的氧化低密度脂蛋白 (oxLDL)，发现 CD46 和 CD59 部分通过其在外泌体和凋亡小体中的释放而在 RPE 细胞中减少。补体调节剂的释放可能会损害 RPE 细胞上的补体调节，并导致 AMD 发展过程中外层视网膜和布鲁赫膜的病变形成。