Glaucoma and Retinal Neurodegeneration Research Group, Visual Neurosciences Department, University College London Institute of Ophthalmology, Bath Street, London EC1V 9EL, United Kingdom.
Exp Eye Res. 2010 Nov;91(5):554-66. doi: 10.1016/j.exer.2010.08.009. Epub 2010 Aug 26.
In glaucoma, the major cause of global irreversible blindness, there is an urgent need for treatment modalities that directly target the RGCs. The discovery of an alternative therapeutic approach, independent of IOP reduction, is highly sought after, due to the indirect nature and limited effectiveness of IOP lowering therapy in preventing RGC loss. Several mechanisms have been implicated in initiating the apoptotic cascade in glaucomatous retinopathy and numerous drugs have been shown to be neuroprotective in animal models of glaucoma. These mechanisms and their potential treatment include excitotoxicity, protein misfolding, mitochondrial dysfunction, oxidative stress, inflammation and neurotrophin deprivation. All of these mechanisms ultimately lead to programmed cell death with loss of RGCs. In this article we summarize the mechanisms involved in glaucomatous disease, highlight the rationale for neuroprotection in glaucoma management and review current potential neuroprotective strategies targeting RGCs from the laboratory to the clinic.
在青光眼这种全球主要的不可逆致盲疾病中，人们迫切需要能够直接针对视网膜神经节细胞（RGCs）的治疗方法。由于眼压降低疗法在预防 RGC 损失方面的间接性和有限效果，因此，人们非常希望找到一种不依赖于眼压降低的替代治疗方法。在青光眼性视网膜病变中，有几种机制被牵涉到引发细胞凋亡级联反应，并且已经有许多药物在青光眼动物模型中显示出神经保护作用。这些机制及其潜在的治疗方法包括兴奋性毒性、蛋白质错误折叠、线粒体功能障碍、氧化应激、炎症和神经营养因子剥夺。所有这些机制最终都会导致 RGC 程序性细胞死亡。在本文中，我们总结了青光眼疾病中涉及的机制，强调了青光眼管理中神经保护的基本原理，并综述了目前从实验室到临床针对 RGC 潜在的神经保护策略。
