School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Life Sci. 2020 Dec 1;262:118462. doi: 10.1016/j.lfs.2020.118462. Epub 2020 Sep 19.
Neurodegeneration of the optic nerve and retinal ganglion cells (RGCs) leads to progressive vision loss. As part of the central nervous system, RGCs show limited ability to regenerate and there is extensive search for neuroprotective agents for optic nerve damage. Methylene blue (MB) exhibits beneficial effects against various neurodegenerative diseases of the central nervous system. However, the mechanisms associated with its putative protection on neuronal survival and regeneration remain obscure. This study used the optic nerve transection model to examine the effects of MB on RGC survival, the expression of regenerative marker GAP-43 in RGCs and microglial activation.
Axons of RGCs were injured by cutting the optic nerve. MB was injected intravitreally either immediately post-injury or delayed to 3 days post-injury. Using immunohistochemical staining, surviving RGCs, GAP-43-positive RGCs and microglial cells were quantified in wholemount retinas 7 days post-injury.
Both immediate and delayed (a more clinically realistic situation) intravitreal injection of MB promoted RGC survival. MB also increased the number of GAP-43-positive RGCs, suggesting an enhanced ability of RGCs to regenerate. This was exemplified by the regenerative sprouting of axon-like processes from injured RGCs after MB treatment. The increase in RGC survival and GAP-43 expression correlated with an increase in the number of microglial cells.
These results reveal that MB has survival-promoting and growth-promoting effects on RGCs after optic nerve injury. Together with the established safety profile of MB in humans, MB is a promising treatment for neurodegeneration and injury of the optic nerve.
视神经和视网膜神经节细胞 (RGC) 的神经退行性变导致进行性视力丧失。作为中枢神经系统的一部分，RGC 的再生能力有限，因此广泛寻找视神经损伤的神经保护剂。亚甲蓝 (MB) 对中枢神经系统的各种神经退行性疾病表现出有益的作用。然而，其对神经元存活和再生的潜在保护作用的机制仍不清楚。本研究使用视神经横断模型来研究 MB 对 RGC 存活、RGC 中再生标志物 GAP-43 的表达以及小胶质细胞激活的影响。
通过切割视神经损伤 RGC 的轴突。MB 或在损伤后立即或延迟至 3 天后通过玻璃体内注射给药。在损伤后 7 天通过全视网膜免疫组织化学染色来定量存活的 RGC、GAP-43 阳性的 RGC 和小胶质细胞。
立即和延迟（更符合临床实际情况）玻璃体内注射 MB 均促进了 RGC 的存活。MB 还增加了 GAP-43 阳性的 RGC 数量，表明 RGC 再生能力增强。MB 处理后，损伤的 RGC 长出轴突样过程的再生性发芽就是一个例证。RGC 存活和 GAP-43 表达的增加与小胶质细胞数量的增加相关。
这些结果表明，MB 在视神经损伤后对 RGC 具有存活促进和生长促进作用。结合 MB 在人类中的既定安全性，MB 是治疗神经退行性变和视神经损伤的有前途的治疗方法。
