Normal tension glaucoma (NTG) is a progressive neurodegenerative disease in glaucoma families. Typical glaucoma develops because of increased intraocular pressure (IOP), whereas NTG develops despite normal IOP. As a subtype of open-angle glaucoma, NTG is characterized by retinal ganglion cell (RGC) degeneration, gradual loss of axons, and injury to the optic nerve. The relationship between glutamate excitotoxicity and oxidative stress has elicited great interest in NTG studies. We recently reported that suppressing collapsin response mediator protein 2 (CRMP2) phosphorylation in S522A CRMP2 mutant (CRMP2 KIKI) mice inhibited RGC death in NTG mouse models. This study evaluated the impact of the natural compounds huperzine A (HupA) and naringenin (NAR), which have therapeutic effects against glutamate excitotoxicity and oxidative stress, on inhibiting CMRP2 phosphorylation in mice intravitreally injected with N-methyl-d-aspartate (NMDA) and GLAST mutant mice. Results of the study demonstrated that HupA and NAR significantly reduced RGC degeneration and thinning of the inner retinal layer, and inhibited the elevated CRMP2 phosphorylation. These treatments protected against glutamate excitotoxicity and suppressed oxidative stress, which could provide insight into developing new effective therapeutic strategies for NTG.

正常眼压性青光眼（NTG）是青光眼家族中一种进行性神经退行性疾病。典型的青光眼是由于眼内压 (IOP) 升高而发生的，而 NTG 是在 IOP 正常的情况下发生的。作为开角型青光眼的一种亚型，NTG 的特点是视网膜神经节细胞 (RGC) 变性、轴突逐渐丧失以及视神经损伤。谷氨酸兴奋性毒性和氧化应激之间的关系引起了人们对 NTG 研究的极大兴趣。我们最近报道，抑制 S522A CRMP2 突变体 (CRMP2 KIKI) 小鼠中的塌陷素反应介导蛋白 2 (CRMP2) 磷酸化可抑制 NTG 小鼠模型中的 RGC 死亡。本研究评估了天然化合物石杉碱甲 (HupA) 和柚皮素 (NAR) 对谷氨酸兴奋毒性和氧化应激具有治疗作用，对玻璃体内注射N-甲基-d-天冬氨酸 (NMDA)的小鼠抑制 CMRP2 磷酸化的影响和 GLAST 突变小鼠。研究结果表明，HupA 和 NAR 显着减少 RGC 变性和视网膜内层变薄，并抑制 CRMP2 磷酸化升高。这些治疗方法可以防止谷氨酸兴奋性毒性并抑制氧化应激，这可以为开发新的有效 NTG 治疗策略提供见解。