State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-Sen University, Guangzhou, 510060, China.
Mol Neurobiol. 2022 May;59(5):3052-3072. doi: 10.1007/s12035-022-02781-y. Epub 2022 Mar 9.
Axons of adult neurons in the mammalian central nervous system generally fail to regenerate by themselves, and few if any therapeutic options exist to reverse this situation. Due to a weak intrinsic potential for axon growth and the presence of strong extrinsic inhibitors, retinal ganglion cells (RGCs) cannot regenerate their axons spontaneously after optic nerve injury and eventually undergo apoptosis, resulting in permanent visual dysfunction. Regarding the extracellular environment, research to date has generally focused on glial cells and inflammatory cells, while few studies have discussed the potentially significant role of interneurons that make direct connections with RGCs as part of the complex retinal circuitry. In this study, we provide a novel angle to summarize these extracellular influences following optic nerve injury as "intercellular interactions" with RGCs and classify these interactions as synaptic and non-synaptic. By discussing current knowledge of non-synaptic (glial cells and inflammatory cells) and synaptic (mostly amacrine cells and bipolar cells) interactions, we hope to accentuate the previously neglected but significant effects of pre-synaptic interneurons and bring unique insights into future pursuit of optic nerve regeneration and visual function recovery.
哺乳动物中枢神经系统中的成年神经元轴突通常自身无法再生，并且几乎没有任何治疗选择可以逆转这种情况。由于轴突生长的内在潜力较弱，以及存在强烈的外在抑制物，视网膜神经节细胞 (RGC) 在视神经损伤后不能自发地再生其轴突，最终会发生细胞凋亡，导致永久性视觉功能障碍。关于细胞外环境，迄今为止的研究通常集中在神经胶质细胞和炎症细胞上，而很少有研究讨论作为复杂视网膜回路的一部分与 RGC 直接相连的中间神经元的潜在重要作用。在这项研究中，我们提供了一个新的角度来总结视神经损伤后的这些细胞外影响，将其称为与 RGC 的“细胞间相互作用”，并将这些相互作用分为突触和非突触。通过讨论非突触（神经胶质细胞和炎症细胞）和突触（主要是无长突细胞和双极细胞）相互作用的现有知识，我们希望强调以前被忽视但却非常重要的前突中间神经元的作用，并为未来追求视神经再生和视觉功能恢复提供独特的见解。
