视神经属于中枢神经的一部分,损伤后难以再生。视神经损伤通常伴随视网膜神经节细胞(retinal ganglion cells,RGCs)的持续性凋亡及视神经变性坏死,引起视力损害甚至完全失明。目前针对视神经再生的基础研究主要集中于保护和维持视神经损伤后RGCs的存活、促进RGCs轴突再生及重建视神经功能。本文以RGCs保护、轴突再生及视神经功能重建等为关键词,查询国内外最新视神经再生研究类文献,并分析整理,从抗氧化应激、提供外源性细胞因子、炎症刺激、抗胶质瘢痕、基因调控等方面阐述近年的视神经再生研究进展,以期对后续的基础研究开展及临床转化有所帮助。
Optic nerves are a part of the central nervous system, which is difficult to regenerate after injury. Optic nerve injury is usually accompanied by continuous apoptosis of retinal ganglion cells (RGCs) and degeneration or necrosis of optic nerves, resulting in visual impairment or even complete blindness. At present, the basic research on optic nerve regeneration mainly focuses on protecting and maintaining the survival of RGCs after optic nerve injury, promoting RGCs axon regeneration, and reconstructing optic nerve function. In this paper, RGCs protection,axon regeneration, and optic nerve function reconstruction are used as key words to collect the latest domestic and foreign literatures on optic nerve regeneration. The research progress of optic nerve regeneration in recent years was reviewed from the aspects of antioxidant stress, provision of exogenous cytokines, inflammatory stimulation, anti-glial scar, gene regulation and so on, in order to help the follow-up basic research and clinical translation.
内源性干细胞在组织的损伤修复过程中组织相容性好、致瘤风险低,相较于外源性干细胞具有不需要体外扩增和培养、疾病传播风险低的优点,在细胞治疗领域具有显著优势。现在已经有多种使用内源性干细胞进行疾病治疗的成熟方式,应用领域包括了全身各种器质性和功能性疾病。在眼组织中,晶状体具有终生生长的能力且便于观察,是实现再生修复的突破点。哺乳动物中晶状体再生的实现有赖于晶状体内源性干细胞的定位和改良手术方式,以保留晶状体干细胞,并创造适合晶状体再生的微环境。对再生后的晶状体蛋白质组成分析,发现其类似成熟晶状体,而非胚胎期的晶状体,提示晶状体再生的调控与胚胎期的诱导发生并不相同;而调控晶状体再生的策略不仅着眼于干细胞的激活和正确分化的诱导,对其上皮间质转化过程也需要进行调控。在未来,为将晶状体再生的经验应用于其他眼组织中,动员内源性干细胞并促进其生长,可以添加细胞有效成分,比如外泌体、线粒体、小分子化合物等,模拟细胞应激;此外,还可以通过手术或生物材料辅助,恢复晶状体结构和环境。
Endogenous stem cells have significant advantages in cell therapy for excellent histocompatibility, low tumorigenicity risk, unnecessity for in vitro expansion and culture, and low disease transmission risk. There have been some applications for endogenous stem cells in treating diseases, targeting some organic and functional diseases throughout the body. In ocular tissue, the lens is a breakthrough for regenerative therapy due to its potential to grow throughout life and observation accessibility. Achieving lens regeneration in adult mammals attributes to some prerequisites. Firstly, the location of endogenous stem cells in the lens has been identified. Then, surgical approaches have been advanced to preserve lens stem cells and create a microenvironment suitable for lens regeneration. Protein compositional analysis of the regenerated lens reveals that it is similar to a mature lens rather than an embryonic lens, suggesting that the regulation of lens regeneration is not the same as the induction of embryonic onset. The strategy for regulating lens regeneration needs to focus not only on the activation and proper differentiation of stem cells but also on regulating the process of epithelial mesenchymal transition (EMT). In the future, in order to apply the experiences of lens regeneration to other ocular tissues, to mobilize endogenous cells and promote their growth, some strategies could be used. These strategies include mimicking cellular stress via the addition of cellular active ingredients, such as exosome, mitochondria, and small molecular compounds. Additionally, we can also try to restore lens tissue structure and microenvironment through surgical or biomaterial assistance.