Eye-brain axis: the crosstalk between neurons and immune cells

Interactions between the nervous system and immune system within the eye have been identified as a key regulatory mechanism underlying both ocular homeostasis and the progression of blinding diseases. The eye is a specialized extension of the central nervous system that encompasses a complex network of communication between neuronal components and resident immune cells, such as microglia, macrophages, lymphocytes, and dendritic cells. These neuro-immune interactions are central to ocular health and disease. They facilitate immune surveillance, tissue repair, and neurotrophic maintenance under physiological settings. However, in pathological states, disruption of this network causes persistent neuroinflammation and neurodegeneration. This functional change highlights the dual relevance of the neuro-immune axis in both disease progression and neuroprotection. It reflects a shared pathogenic mechanism underpinning major blinding diseases, such as glaucoma, diabetic retinopathy, and uveitis. In this review, we summarize research on the cellular and molecular mechanisms underlying neuro-immune communication along the eye-brain axis, emphasizing its roles in maintaining homeostasis, mediating pathology, and providing a source of therapeutic targets. We argue that the intraocular neuro-immune network shows promise for the development of precisely targeted, mechanism-based therapeutic strategies, in addition to serving as a unifying factor for ocular disorders.