Neural modulation of ocular immunity: Exploring a sympathetic-macrophage neuroimmune link in the human ciliary body

The ciliary body (CB) represents an immunoregulatory compartment for the ocular system and we questioned whether local immune regulation in the CB in humans could be under neural control. In this study, we explored whether the human CB contains a sympathetic-macrophage neuroimmune link. Seven right eyes from donated cadavers (five male, two female) were enucleated. After removal of the cornea, lens, and vitreous body, each eye was divided into quadrants. One quadrant per eye was processed for light microscopy to assess overall morphology, general and sympathetic nerve presence, varicosities, macrophages, and the proximity of sympathetic nerves to macrophages. Additional quadrants (whole-mount samples) were examined with three-dimensional (3D) confocal microscopy to visualize the spatial relationship between sympathetic nerves and macrophages and to determine whether these macrophages expressed β₂-adrenergic receptors. Our study shows that the human CB contains sympathetic nerves of which a significant amount was spatially associated to β2-adrenergic receptor expressing macrophages. The current study provides morphological evidence for a possible sympathetic-macrophage ocular neuroimmune link in humans which may constitute a novel field for the study of degenerative and inflammatory eye disease. Further understanding of the CB sympathetic nerves and their immunomodulatory capacity is needed for the development of future therapeutics.