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Yashar Seyed-Razavi, Holly Chinnery, Paul McMenamin; Nerve trunks in the peripheral cornea and limbus have an intimate association with macrophages. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2593.
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The cornea is highly innervated and it is known these nerves are responsive to local injury and systemic disease such as diabetes. The cornea contains resident populations of myeloid derived cells including epithelial dendritic cells (Langerhans cells), stromal dendritic cells and stromal macrophages. However, to our knowledge there have been no specific studies examining the co-localisation of nerves and macrophages despite the known role of the immune system in neural regeneration after injury.
Naive and injured corneas from WT BALB/c, WT C57BL/6, CD11c eYFP and Cx3cr1 GFP transgenic mice were fixed, stained as flatmounts with antibodies against nerves (Beta-III tubulin and WGA) and macrophages (Iba-1 and MHC class II), and examined by confocal microscopy. Imaris 3D software was utilised to quantitate physical neuro-immune interactions in the central, paracentral and peripheral cornea.
Direct interactions were evident between nerve fibres in the central cornea and epithelial CD11c+ DCs and sub-basal Iba-1+ macrophages. The most distinctive association between nerves and macrophages was noted between stromal Cx3cr1+ Iba-1+ MHC class II+ macrophages and peri-limbal nerve trunks. WT BALB/c mice had a greater number of neuro-immune interactions (2.3±0.3 (mean±SEM)/100µm) than C57BL/6J mice (1.5±0.1/100µm). Lectin staining revealed that macrophage processes intimately interdigitated between Schwann cells. There was no topographical difference in the circumferential distribution (i.e. temporal-nasal, superior-inferior) of macrophage-nerve fibre interactions.
This study is the first to highlight a direct physical association between nerves and resident immune cells in the murine cornea. These normal data may serve as the basis for future studies into the propagation of innate immune responses as well as having implications in the study of neurotrophic keratitis and peripheral neuropathy.
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