原发性开角型青光眼的免疫机制

New insights into immune mechanisms in primary open angle glaucoma

非眼压因素造成的视网膜神经节细胞(RGC)及其轴突发生原发性损害的机制,以及原发性开角型青光眼(POAG)进展过程中RGC/轴突不依赖于眼压的继发性损害机制均是POAG发病机制中亟待回答的问题。视网膜是中枢神经系统(CNS)的一部分,POAG与CNS神经元退行性疾病的发病机制在一定程度上具有相似性,其中神经免疫-炎症与神经元变性发生与演进的关系是共同性核心问题。CNS神经元退行性疾病的神经免疫-炎症相关研究进展为POAG的研究突破提供了新的启示。本文从神经免疫学角度入手,聚焦于非特异性免疫的小胶质细胞和特异性免疫的T淋巴细胞,总结CNS神经元变性疾病的研究进展,并且整合POAG相关免疫机制研究的新发现,以期对这一主题建立理论假说构架,为进一步探索POAG发病机制奠定基础。推测POAG免疫损伤的机制为:神经元损伤相关抗原激活小胶质细胞释放促炎症因子,外周循环白细胞黏附性增强,血-视网膜屏障通透性改变;抗原呈递过程通过多个途径实现;在次级淋巴器官,抗原递呈细胞呈递抗原给T细胞,形成RGC或轴突抗原特异性的T细胞克隆,并分裂和增生形成大量抗原特异性T细胞经血循环系统进入视网膜,造成视网膜神经元免疫炎性损伤扩大。(眼科,2021,30:5-10)

Investigation into mechanisms that are independent of IOP,but cause initial or secondary damages to retinal ganglion cells and/or their axons is imperative.The retina is a part of the central nervous system(CNS).POAG and other neurodegenerative diseases may share some common pathological mechanisms,of which the neuroimmunity-inflammation plays a pivotal role.State-of-the-art findings on immune mechanisms of CNS neurodegeneration may shed some novel insight into the exploration of POAG pathogenesis.From a perspective of neuroscience and immunology,focusing on microglia and T lymphocytes in light of the latest findings in immune mechanisms of neurodegeneration,we have therefore established a novel theoretical structure integrating existing knowledge on the pathogenesis of POAG.Altogether,we speculate that mechanisms of POAG immune injury is as follows:neuron damage-associated antigens activate microglia releasing pro-inflammatory factors and increasing the adhesion of peripheral circulating leukocytes,and thereafter the permeability of BRB changes;the antigen presentation process may be achieved through diverse pathways;in lymphoid organs,T cells clone,proliferate and differentiate induced by the interaction with APCs,and then antigen-specific T cells enter the retina through the BRB,causing the exacerbation of immune-inflammatory damage to retinal neurons.(Ophthalmol CHN,2021,30:5-10)