Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
National Clinical Research Center for Eye Diseases, Shanghai, China.
CNS Neurosci Ther. 2023 Jun;29 Suppl 1(Suppl 1):146-160. doi: 10.1111/cns.14165. Epub 2023 Mar 16.
Optic nerve injury is a leading cause of irreversible blindness worldwide. The retinal ganglion cells (RGCs) and their axons cannot be regenerated once damaged. Therefore, reducing RGC damage is crucial to prevent blindness. Accordingly, we aimed to investigate the potential influence of the gut microbiota on RGC survival, as well as the associated action mechanisms.
We evaluated the effects of microbiota, specifically Bifidobacterium, on RGC. Optic nerve crush (ONC) was used as a model of optic nerve injury. Vancomycin and Bifidobacterium were orally administered to specific pathogen-free (SPF) mice.
Bifidobacterium promoted RGC survival and optic nerve regeneration. The administration of Bifidobacterium inhibited microglia activation but promoted Müller cell activation, which was accompanied by the downregulation of inflammatory cytokines and upregulation of neurotrophic factors and retinal ERK/Fos signaling pathway activation.
Our study demonstrates that Bifidobacterium-induced changes in intestinal flora promote RGC survival. The protective effect of Bifidobacterium on RGC can be attributed to the inhibition of microglia activation and promotion of Müller cell activation and the secondary regulation of inflammatory and neurotrophic factors.
视神经损伤是全球范围内导致不可逆失明的主要原因。视网膜神经节细胞(RGC)及其轴突一旦受损就无法再生。因此,减少 RGC 损伤对于预防失明至关重要。因此,我们旨在研究肠道微生物群对 RGC 存活的潜在影响及其相关作用机制。
我们评估了微生物群,特别是双歧杆菌对 RGC 的影响。视神经挤压(ONC)被用作视神经损伤的模型。万古霉素和双歧杆菌通过口服给予无菌(SPF)小鼠。
双歧杆菌促进了 RGC 的存活和视神经的再生。双歧杆菌的给药抑制了小胶质细胞的激活,但促进了 Muller 细胞的激活,这伴随着炎症细胞因子的下调和神经营养因子的上调以及视网膜 ERK/Fos 信号通路的激活。
我们的研究表明,双歧杆菌诱导的肠道菌群变化促进了 RGC 的存活。双歧杆菌对 RGC 的保护作用归因于抑制小胶质细胞的激活和促进 Muller 细胞的激活,以及对炎症和神经营养因子的二次调节。