摘要
Müller胶质细胞(MGC)是视网膜中主要的放射状神经胶质细胞,贯穿整个视网膜层,在维持神经元稳态、调节代谢和参与损伤修复中发挥关键作用。其反应模式在不同物种间存在显著差异,如低等脊椎动物的MGC具备重编程和再生能力,而哺乳动物主要表现为反应性胶质增生。在糖尿病视网膜病变中,MGC在高糖环境下被激活,释放血管内皮生长因子和炎症因子,破坏血视网膜屏障,导致黄斑水肿,并参与中心凹形态的维持与修复。在玻璃体视网膜界面疾病中,MGC作为内界膜的主要来源和机械支架,参与黄斑裂孔和视网膜前膜的形成与修复。在缺血性视网膜病变中,MGC通过缺氧诱导因子-1α等通路调控病理性血管生成,并与小胶质细胞互作加剧炎症损伤。在青光眼等神经退行性疾病中,MGC通过调节胆固醇代谢和释放促炎因子,形成神经毒性微环境,促进视网膜神经节细胞死亡。近年来,围绕Janus激酶/信号转导与转录激活因子等信号通路的研究揭示了MGC再生潜能的分子基础。尽管哺乳动物MGC再生能力有限,但通过基因治疗(如过表达神经源性分化因子1)、药物干预(如使用成纤维细胞生长因子21)及细胞重编程等新策略,可在一定程度上激活其再生潜能,促进视网膜神经元再生。未来的治疗策略应着眼于精确调控MGC的反应,最大化其神经保护作用,同时抑制胶质瘢痕形成,为视网膜退行性疾病的防治提供新的方向。
Müller glial cells(MGCs)are the principal radial glial cells in the retina,extending across all retinal layers and playing a crucial role in maintaining neuronal homeostasis,regulating metabolism,and participating in damage repair.The response patterns of MGCs differ significantly between species:in lower vertebrates,MGCs possess reprogramming and regenerative abilities,while in mammals,they primarily exhibit reactive gliosis.In diabetic retinopathy,MGCs are activated in a hyperglycemic environment,releasing vascular endothelial growth factors and inflammatory cytokines,which disrupt the blood-retinal barrier,leading to macular edema and participating in the maintenance and repair of foveal morphology.In vitreoretinal interface diseases,MGCs serve as the primary source of the internal limiting membrane and provide mechanical support,contributing to the formation and repair of macular holes and epiretinal membranes.In ischemic retinal diseases,MGCs regulate pathological angiogenesis through pathways such as hypoxia-inducible factor-1α,interacting with microglial cells to exacerbate inflammatory damage.In neurodegenerative diseases such as glaucoma,MGCs regulate cholesterol metabolism and release pro-inflammatory cytokines,creating a neurotoxic microenvironment that promotes retinal ganglion cell death.Recent studies investigating signaling pathways,such as Janus kinase/signal transducer and activator of transcription,have revealed the molecular basis underlying the regenerative potential of MGCs.Although the regenerative capacity of MGCs is limited in mammals,strategies such as gene therapy(e.g.,overexpression of neurogenic differentiation factor 1),pharmacological interventions(e.g.,fibroblast growth factor 21),and cell reprogramming can partially reactivate their regenerative potential and promote retinal neuron regeneration.Future therapeutic strategies should focus on precisely regulating MGC responses to maximize their neuroprotective effects while suppressing glial scar formation,providing new directions for the prevention and treatment of retinal degenerative diseases.
作者
欧桐彤
陆方
Ou Tongtong;Lu Fang(Department of Ophthalmology,West China Hospital,Sichuan University,Chengdu 610041,China)
出处
《中华眼底病杂志》
北大核心
2025年第11期882-887,共6页
Chinese Journal of Ocular Fundus Diseases
基金
国家自然科学基金(82201212)
四川省自然科学基金(2023NSFSC1670)。
