Regulatory mechanisms of retinal ganglion cell death in normal tension glaucoma and potential therapies

被引:24
作者
Shen, Wen-Cui [1 ]
Huang, Bing-Qing [2 ]
Yang, Jin [1 ]
机构
[1] Nankai Univ, Tianjin Eye Hosp & Eye Inst, Tianjin Key Lab Ophthalmol & Visual Sci, Tianjin, Peoples R China
[2] Chinese Acad Med Sci & Peking Union Med Coll, Inst Hematol & Blood Dis Hosp, Natl Clin Res Ctr Blood Dis, State Key Lab Expt Hematol, Tianjin, Peoples R China
关键词
autophagy; endothelin; 1; glutamate neurotoxicity; inhibitor; nerve regeneration; neuroinflammation; normal tension glaucoma; oxidative stress; retinal ganglion cell; vasoconstriction; PRIMARY OPEN-ANGLE; OPTIC-NERVE DAMAGE; OXIDATIVE STRESS; CLINICAL-FEATURES; DEFICIENT MICE; VALPROIC ACID; E50K MUTATION; MULLER CELLS; MOUSE MODEL; AUTOPHAGY;
D O I
10.4103/1673-5374.344831
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Normal tension glaucoma (NTG) is a multifactorial optic neuropathy characterized by normal intraocular pressure, progressive retinal ganglion cell (RGC) death, and glaucomatous visual field loss. Recent studies have described the mechanisms underlying the pathogenesis of NTG. In addition to controlling intraocular pressure, neuroprotection and reduction of RGC degeneration may be beneficial therapies for NTG. In this review, we summarized the main regulatory mechanisms of RGC death in NTG, including autophagy, glutamate neurotoxicity, oxidative stress, neuroinflammation, immunity, and vasoconstriction. Autophagy can be induced by retinal hypoxia and axonal damage. In this process, ischemia can cause mutations of optineurin and activate the nuclear factor-kappa B pathway. Glutamate neurotoxicity is induced by the over-stimulation of N-methyl-D-aspartate membrane receptors by glutamate, which occurs in RGCs and induces progressive glaucomatous optic neuropathy. Oxidative stress also participates in NTG-related glaucomatous optic neuropathy. It impairs the mitochondrial and DNA function of RGCs through the apoptosis signal-regulating kinaseJUN N-terminal kinase pathway. Moreover, it increases inflammation and the immune response of RGCs. Endothelin 1 causes endothelial dysfunction and impairment of ocular blood flow, promoting vasospasm and glaucomatous optic neuropathy, as a result of NTG. In conclusion, we discussed research progress on potential options for the protection of RGCs, including TANK binding kinase 1 inhibitors regulating autophagy, N-methyl-D-aspartate receptor antagonists inhibiting glutamate toxicity, ASK1 inhibitors regulating mitochondrial function, and antioxidants inhibiting oxidative stress. In NTG, RGC death is regulated by a network of mechanisms, while various potential targets protect RGCs. Collectively, these findings provide insight into the pathogenesis of NTG and potential therapeutic strategies.
引用
收藏
页码:87 / 93
页数:7
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