视网膜星形胶质细胞在视网膜血管生成中的研究进展OA

Retinal astrocytes,as key elements of the neurovascular unit,fulfill a multitude of roles in preserving retinal homeostasis.These roles include providing structural support,supplying nutrients,facilitating metabolic waste clearance,and regulating immune responses.This review presents a systematic and in-depth exploration of their embryonic origin,molecular markers,as well as the fundamental disparities between them and Müller cells in terms of developmental origin,spatial distribution,and functional coupling.Under physiological conditions,astrocytes migrate outward to form a"honeycomb"-like template.This template acts as a guiding framework for the orderly migration of vascular endothelial cells,facilitating the establishment of the superficial vascular plexus.This is achieved through the secretion of N-cadherin,fibronectin,and laminin.The end-feet of astrocytes extensively wrap around the capillary basement membrane and are actively involved in the formation of the blood-retinal barrier.When it comes to nutrient supply,astrocytes take up glucose via glucose transporter type 1(GLUT1).Subsequently,they generate lactate through aerobic glycolysis and store glycogen as an emergency energy reserve to meet potential demands.In terms of metabolic waste clearance,as the primary producers of glutathione in the retina,astrocytes are capable of eliminating reactive oxygen species and converting glutamate into non-toxic glutamine.This process effectively shields neurons from oxidative stress and excitotoxicity,thereby maintaining the normal function of the retinal neural network.Under pathological conditions,such as hypoxia and inflammation,astrocytes exhibit a dual role in either promoting or inhibiting retinal neovascularization(RNV).Hypoxia leads to the stabilization of hypoxia-inducible factor-1α(HIF-1α)and activates the nuclear factor kappa-B(NF-κB)pathway.This activation,in turn,promotes the release of factors like vascular endothelial growth factor-A(VEGF-A),fibroblast growth factor 2(FGF2),interleukin-6(IL-6),and matrixmetalloproteinase-2/9(MMP-2/9),ultimately resulting in pathological RNV.On the contrary,astrocytes can also polarize into A2-type reactive astrocytes.These reactive astrocytes secrete thrombospondin-1(TSP-1),pigment epithelium-derived factor(PEDF),and exosomes loaded with anti-angiogenic proteins.These secretions inhibit excessive vascular proliferation and facilitate orderly repair,thereby counteracting the pathological process of RNV.A more profound understanding of their precise regulatory mechanisms of retinal astrocytes may pave the way for the development of targeted RNV therapies.These potential therapies could involve strategies such as safeguarding the integrity of astrocyte network,reprogramming the phenotypes of reactive astrocyte,and utilizing exosome-based delivery systems to precisely modulate the biological functions of astrocytes and achieve effective treatment of RNV.