Abstract：
Glaucoma is a complex multifactorial eye disease manifesting in retinal ganglion cell (RGC) death and optic nerve degeneration, ultimately causing irreversible vision loss. Research in recent years has significantly enhanced our understanding of RGC degenerative mechanisms in glaucoma. It is evident that high intraocular pressure (IOP) is not the only contributing factor to glaucoma pathogenesis. The equilibrium of pro-survival and pro-death signalling pathways in the retina strongly influences the function and survival of RGCs and optic nerve axons in glaucoma. Molecular evidence from human retinal tissue analysis and a range of experimental models of glaucoma have significantly contributed to unravelling these mechanisms. Accumulating evidence reveals a wide range of molecular signalling pathways that can operate -either alone or via intricate networks - to induce neurodegeneration. The roles of several molecules, including neurotrophins, interplay of intracellular kinases and phosphates, caveolae and adapter proteins, serine proteases and their inhibitors, nuclear receptors, amyloid beta and tau, and how their dysfunction affects retinal neurons are discussed in this review. We further underscore how anatomical alterations in various animal models exhibiting RGC degeneration and susceptibility to glaucoma-related neuronal damage have helped to characterise molecular mechanisms in glaucoma. In addition, we also present different regulated cell death pathways that play a critical role in RGC degeneration in glaucoma.
摘要：
青光眼是一种复杂的多因素眼病，表现为视网膜神经节细胞（RGC）死亡和视神经变性，最终导致不可逆的视力丧失。近年来的研究大大增强了我们对青光眼RGC变性机制的理解。很明显，高眼内压（IOP）不是青光眼发病机理的唯一因素。视网膜中促存活和促死亡信号通路的平衡强烈影响青光眼中RGC和视神经轴突的功能和存活。来自人类视网膜组织分析和一系列青光眼实验模型的分子证据对揭示这些机制做出了重大贡献。越来越多的证据表明，广泛的分子信号通路可以单独或通过复杂的网络来诱导神经变性。几种分子的作用，包括神经营养因子,细胞内激酶和磷酸盐的相互作用，Caveolae和衔接蛋白，丝氨酸蛋白酶及其抑制剂,核受体,淀粉样β和tau，以及它们的功能障碍如何影响视网膜神经元在这篇综述中进行了讨论。我们进一步强调了表现出RGC变性和对青光眼相关神经元损伤易感性的各种动物模型的解剖学改变如何帮助表征青光眼的分子机制。此外,我们还提出了不同的调节细胞死亡途径，这些途径在青光眼的RGC变性中起关键作用。
