炎症与年龄相关性黄斑变性

Inflammation and age-related macular degeneration

年龄相关性黄斑变性(AMD)是中老年人常见的致盲性眼病之一,特征性改变是玻璃膜疣(drusen)形成和脉络膜新生血管(CNV),确切发病机制不清,衰老、营养失衡和遗传等多种因素参与其发病。近年来研究发现机体慢性炎症和补体活化等免疫机制在其发病中占有重要作用,从AMD患者病灶组织及玻璃膜疣中发现有巨噬细胞和补体成分沉积,玻璃膜疣的形成与补体成分在Bruch膜上的活化以及脉络膜巨噬细胞吞噬功能下调有关,CNV的形成与补体成分活化、炎症刺激以及脉络膜巨噬细胞聚集活化有关,补体因子H的基因多态性也与AMD的发生有关。脂褐素碎片可刺激视网膜色素上皮细胞活化并分泌炎性细胞因子或血管生长因子,促进CNV的形成;长期光氧化损伤可导致视网膜蛋白变性形成新抗原,并刺激机体产生自身抗体,导致补体活化和巨噬细胞聚集,参与玻璃膜疣的形成和CNV发生。综上证据表明慢性炎症和补体活化等免疫学改变在AMD发生中起着重要作用,这就提示抗炎治疗可作为AMD患者的有效辅助治疗措施。

Age-related macular degeneration（AMD） is a leading cause of blindness worldwide.The characters are the drusen formation and the development of choroidal neovascularization（CNV）,its etiology and pathogenesis remain unclear.Aging,nutrition and genetics were related to the etiology of AMD.Recent findings suggest that the chronic inflammation and complements activation participated in the AMD pathogenesis.From the Bruch membrane and the drusen,the deposits of macrophages and complement contents were found.The formation of drusen was related to the complement activation on the Bruch membrane and the lower phagocytic abilities of choroidal macrophages.The development of CNV was related to the complement activation,inflammation stimulation and choroidal macrophages accumulation.The polymorphisms of complement factor H was related to the AMD.The lipofuscin can stimulate the retinal pigment epithelium cells activation and create the inflammatory mediators and vascular growth factors,and improve the development of CNV.Cumulative oxidative stress can lead to the retinal proteins degeneration and neoantigens formation,and stimulate the immune systems to produce the autoantibodies and cause the complements activation and macrophages accumulation during the formation of drusen and CNV.The abovementioned evidences indicate that the chronic inflammation and complement activation are involved in the etiology of AMD and indicate the anti-inflammatory agent as the alternative therapy for AMD patients.This article summarized the immunological mechanisms in the pathogenesis of AMD.