Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan; Department of Molecular Neuroscience, St. Marianna University Graduate School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.
Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, 216-8511, Japan.
Mol Aspects Med. 2023 Dec;94:101217. doi: 10.1016/j.mam.2023.101217. Epub 2023 Oct 14.
The optic nerve consists of the glia, vessels, and axons including myelin and axoplasm. Since axonal degeneration precedes retinal ganglion cell death in glaucoma, the preceding axonal degeneration model may be helpful for understanding the molecular mechanisms of optic nerve degeneration. Optic nerve samples from these models can provide information on several aspects of autophagy. Autophagosomes, the most typical organelles expressing autophagy, are found much more frequently inside axons than around the glia. Thus, immunoblot findings from the optic nerve can reflect the autophagy state in axons. Autophagic flux impairment may occur in degenerating optic nerve axons, as in other central nervous system neurodegenerative diseases. Several molecular candidates are involved in autophagy enhancement, leading to axonal protection. This concept is an attractive approach to the prevention of further retinal ganglion cell death. In this review, we describe the factors affecting autophagy, including nicotinamide riboside, p38, ULK, AMPK, ROCK, and SIRT1, in the optic nerve and propose potential methods of axonal protection via enhancement of autophagy.
视神经由神经胶质、血管和轴突组成，包括髓鞘和轴浆。由于轴突变性先于青光眼的视网膜神经节细胞死亡，因此先前的轴突变性模型可能有助于理解视神经变性的分子机制。这些模型的视神经样本可以提供关于自噬的几个方面的信息。自噬体是表达自噬的最典型细胞器，在轴突内比在神经胶质周围更频繁地发现。因此，视神经的免疫印迹结果可以反映轴突中的自噬状态。在其他中枢神经系统神经退行性疾病中，退化的视神经轴突中可能会出现自噬流受损。几种分子候选物参与自噬增强，从而导致轴突保护。这个概念是预防进一步的视网膜神经节细胞死亡的一种有吸引力的方法。在这篇综述中，我们描述了影响视神经自噬的因素，包括烟酰胺核苷、p38、ULK、AMPK、ROCK 和 SIRT1，并提出了通过增强自噬来保护轴突的潜在方法。
