Modulation of the Immune System for the Treatment of Glaucoma.
Modulation of the Immune System for the Treatment of Glaucoma.
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DOI：
10.2174/1570159x15666170720094529
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发表时间：
2018
影响因子：
5.3
通讯作者：
Grus F
中科院分区：
文献类型：
--
作者：
Bell K;Und Hohenstein-Blaul NVT;Teister J;Grus F
目前，降低眼压是治疗青光眼的唯一方法。到目前为止，保护视网膜神经节细胞(RGC)免受凋亡的神经保护策略还很缺乏。近年来，关于免疫系统在青光眼中的作用进行了大量的研究。本综述旨在分析青光眼患者外周免疫系统的变化，以及青光眼视网膜局部免疫细胞的变化。通过将免疫系统分为先天免疫系统和获得性免疫系统，进行了一项系统的文献研究，以寻找在青光眼背景下免疫系统调节的最新方法。此外，还对ClinicalTrials.gov进行了评估，以确定具有翻译背景的研究。我们发现，免疫系统的某些方面，如抗体水平的变化，Toll样受体信号的变化，T细胞和视网膜小胶质细胞的变化，比其他领域，如树突状细胞或巨噬细胞的变化，经历了更多的研究活动。简而言之，临床研究结果显示，青光眼患者血清和房水中对视网膜和视神经抗原的免疫反应性改变，表明自身免疫参与了青光眼神经变性和RGC死亡。在可能由小胶质细胞维持的促炎环境中，在人青光眼视网膜中发现了与浆细胞一起聚集的免疫球蛋白。动物研究表明，在青光眼患者中，抗体(如抗热休克蛋白60和抗髓鞘碱性蛋白)升高会导致自身侵袭性RGC丢失，并与免疫球蛋白沉积和小胶质细胞增加有关。此外，已经进行了关于T淋巴细胞、巨噬细胞以及视网膜局部免疫反应变化的研究，也取得了令人振奋的结果。这一最新文献的总结表明，免疫系统在青光眼的发病机制中确实发挥了作用。已检测到外周固有免疫系统和获得性免疫系统的多种变化，并为进一步研究有价值的治疗靶点提供了空间。我们的结论是，仍然有很大的必要将基础研究得出的结果结合在一起，分析青光眼免疫系统的不同方面，以了解疾病的免疫背景。此外，青光眼患者视网膜的局部免疫变化仍为进一步的治疗靶点留下了空间
At present intraocular pressure (IOP) lowering therapies are the only approach to treat glaucoma. Neuroprotective strategies to protect the retinal ganglion cells (RGC) from apoptosis are lacking to date. Substantial amount of research concerning the role of the immune system in glaucoma has been performed in the recent years. This review aims to analyse changes found in the peripheral immune system, as well as selected local changes of retina immune cells in the glaucomatous retina. By dividing the immune system into the innate and the adaptive immune system, a systematic literature research was performed to find recent approaches concerning the modulation of the immune system in the context of glaucoma. Also ClinicalTrials.gov was assessed to identify studies with a translational context. We found that some aspects of the immune system, such as changes in antibody levels, changes in toll like receptor signalling, T cells and retinal microglial cells, experience more research activity than other areas such as changes in dendritic cells or macrophages. Briefly, results from clinical studies revealed altered immunoreactivities against retinal and optic nerve antigens in sera and aqueous humor of glaucoma patients and point toward an autoimmune involvement in glaucomatous neurodegeneration and RGC death. IgG accumulations along with plasma cells were found localised in human glaucomatous retinae in a pro-inflammatory environment possibly maintained by microglia. Animal studies show that antibodies (e.g. anti- heat shock protein 60 and anti-myelin basic protein) elevated in glaucoma patients provoke autoaggressive RGC loss and are associated with IgG depositions and increased microglial cells. Also, studies addressing changes in T lymphocytes, macrophages but also local immune responses in the retina have been performed and also hold promising results. This recapitulation of recent literature demonstrates that the immune system definitely plays a role in the pathogenesis of glaucoma. Multiple changes in the peripheral innate as well as adaptive immune system have been detected and give room for further research concerning valuable therapeutic targets. We conclude that there still is a great need to bring together the results derived from basic research analysing different aspects of the immune system in glaucoma to understand the immune context of the disease. Furthermore local immune changes in the retina of glaucoma patients still leave room for further therapeutic targets