Department of Immunology, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia.
Centre for Neuroscience Research (NeuRon), Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh, Malaysia.
Front Immunol. 2022 May 16;13:857812. doi: 10.3389/fimmu.2022.857812. eCollection 2022.
Glaucoma is an irreversible sight-threatening disorder primarily due to elevated intraocular pressure (IOP), leading to retinal ganglion cell (RGC) death by apoptosis with subsequent loss of optic nerve fibers. A considerable amount of empirical evidence has shown the significant association between tumor necrosis factor cytokine (TNF; TNFα) and glaucoma; however, the exact role of TNF in glaucoma progression remains unclear. Total inhibition of TNF against its receptors can cause side effects, although this is not the case when using selective inhibitors. In addition, TNF exerts its antithetic roles stimulation of two receptors, TNF receptor I (TNFR1) and TNF receptor II (TNFR2). The pro-inflammatory responses and proapoptotic signaling pathways predominantly mediated through TNFR1, while neuroprotective and anti-apoptotic signals induced by TNFR2. In this review, we attempt to discuss the involvement of TNF receptors (TNFRs) and their signaling pathway in ocular tissues with focus on RGC and glial cells in glaucoma. This review also outlines the potential application TNFRs agonist and/or antagonists as neuroprotective strategy from a therapeutic standpoint. Taken together, a better understanding of the function of TNFRs may lead to the development of a treatment for glaucoma.
青光眼是一种不可逆的致盲性疾病，主要是由于眼内压（IOP）升高，导致视网膜神经节细胞（RGC）通过细胞凋亡死亡，随后视神经纤维丧失。大量的经验证据表明肿瘤坏死因子细胞因子（TNF；TNFα）与青光眼之间存在显著关联；然而，TNF 在青光眼进展中的确切作用仍不清楚。尽管使用选择性抑制剂时并非如此，但针对其受体的 TNF 完全抑制可能会引起副作用。此外，TNF 通过两种受体（TNF 受体 I（TNFR1）和 TNF 受体 II（TNFR2））发挥其拮抗作用。促炎反应和促凋亡信号通路主要通过 TNFR1 介导，而 TNFR2 诱导的神经保护和抗凋亡信号。在这篇综述中，我们试图讨论 TNF 受体（TNFRs）及其信号通路在眼部组织中的参与，重点是青光眼的 RGC 和神经胶质细胞。本综述还从治疗角度概述了 TNFRs 激动剂和/或拮抗剂作为神经保护策略的潜在应用。综上所述，更好地了解 TNFRs 的功能可能会导致开发出治疗青光眼的方法。
