Eye‐Brain Neuroimmune Axis Enables Long‐Term Survival in Glioblastoma by Modulating Brain Immune Surveillance and Neuronal Excitability

ABSTRACT As an anatomical extension of the central nervous system (CNS), the eye harbors rich neural and immune interfaces with the brain. However, the integrated immunological and neurological nexus between the eye and CNS remains unexplored. Here, we identify the existence of an eye–brain neuroimmune axis by analyzing immune and neuronal responses to eye‐brain electrical stimulation (ES). ES‐assisted intravitreal immunization (IVT) prolonged survival in a murine glioblastoma model, with 33.3% of mice surviving to day 50. Mechanistically, the eye‐brain neuroimmune axis serves two pivotal roles: (1) Immune activation: ES accelerates the rapid drainage of intravitreally delivered antigens to deep cervical lymph nodes (dCLNs), bypassing the BBB and triggering robust CNS‐specific immune responses; (2) Disruption of pathological neuron connectivity: the expression of synaptogenic factors and neuronal excitability can also be mediated under ES treatments. These results uncover an unexplored brain neuroimmune connection, offer new insights into the pathophysiology of eye‐brain diseases and suggest promising avenues for precise diagnostic and therapeutic strategies targeting both ocular and CNS disorders.