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A novel association between resident tissue macrophages and nerves in the peripheral stroma of the murine cornea.
Invest Ophthalmol Vis Sci. 2014 Mar 03; 55(3):1313-20.IO

Abstract

PURPOSE

To characterize the interactions between resident macrophage populations and nerves in naïve and injured corneas of the mouse eye.

METHODS

Corneas from wild-type (WT) C57BL/6J, BALB/cJ, and transgenic Cx3cr1-eGFP mice were subjected to a 1-mm central epithelial debridement injury. The eyes were fixed and immunostained as flat mounts with a range of antibodies to identify macrophages, neurons, and Schwann cells. Interactions between nerves and immune cells were analyzed and quantitated using three-dimensional reconstructions of confocal microscopy images. Naïve eyes acted as controls.

RESULTS

A distinctive association between resident immune cells and corneal nerves was noted in the peripheral or perilimbal stromal nerve trunks. These epineurial cells were mostly Cx3cr1(+) Iba-1(+) major histocompatibility complex (MHC) class II(+) F4/80(+) CD11b(+) macrophages. The number of nerve-associated macrophages was greater in WT BALB/c mice than in C57BL/6J mice. There were no qualitative or quantitative differences in the circumferential distribution of nerve-associated macrophages in the cornea. Sterile corneal epithelial debridement led to a dissociation of macrophages from peripheral nerve trunks as early as 2 hours postinjury, with numbers returning to baseline after 72 hours. This dissociation was Cx3cr1 dependent.

CONCLUSIONS

This study is the first to highlight a direct physical association between nerves and resident immune cells in the murine cornea. Furthermore, we reveal that this association in normal eyes is responsive to central corneal epithelial injury and is partly mediated by Cx3cr1 signaling. This association may serve as an indicator of malfunctioning neuroimmune communication in disease states such as neurotrophic keratitis and peripheral neuropathy.

Authors+Show Affiliations

Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Victoria, Australia.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Video-Audio Media

Language

eng

PubMed ID

24458151

Citation

Seyed-Razavi, Yashar, et al. "A Novel Association Between Resident Tissue Macrophages and Nerves in the Peripheral Stroma of the Murine Cornea." Investigative Ophthalmology & Visual Science, vol. 55, no. 3, 2014, pp. 1313-20.
Seyed-Razavi Y, Chinnery HR, McMenamin PG. A novel association between resident tissue macrophages and nerves in the peripheral stroma of the murine cornea. Invest Ophthalmol Vis Sci. 2014;55(3):1313-20.
Seyed-Razavi, Y., Chinnery, H. R., & McMenamin, P. G. (2014). A novel association between resident tissue macrophages and nerves in the peripheral stroma of the murine cornea. Investigative Ophthalmology & Visual Science, 55(3), 1313-20. https://doi.org/10.1167/iovs.13-12995
Seyed-Razavi Y, Chinnery HR, McMenamin PG. A Novel Association Between Resident Tissue Macrophages and Nerves in the Peripheral Stroma of the Murine Cornea. Invest Ophthalmol Vis Sci. 2014 Mar 3;55(3):1313-20. PubMed PMID: 24458151.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel association between resident tissue macrophages and nerves in the peripheral stroma of the murine cornea. AU - Seyed-Razavi,Yashar, AU - Chinnery,Holly R, AU - McMenamin,Paul G, Y1 - 2014/03/03/ PY - 2014/1/25/entrez PY - 2014/1/25/pubmed PY - 2014/5/7/medline KW - Cx3cr1 deficiency KW - cornea KW - dendritic cells KW - nerve associated macrophages KW - sterile injury SP - 1313 EP - 20 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 55 IS - 3 N2 - PURPOSE: To characterize the interactions between resident macrophage populations and nerves in naïve and injured corneas of the mouse eye. METHODS: Corneas from wild-type (WT) C57BL/6J, BALB/cJ, and transgenic Cx3cr1-eGFP mice were subjected to a 1-mm central epithelial debridement injury. The eyes were fixed and immunostained as flat mounts with a range of antibodies to identify macrophages, neurons, and Schwann cells. Interactions between nerves and immune cells were analyzed and quantitated using three-dimensional reconstructions of confocal microscopy images. Naïve eyes acted as controls. RESULTS: A distinctive association between resident immune cells and corneal nerves was noted in the peripheral or perilimbal stromal nerve trunks. These epineurial cells were mostly Cx3cr1(+) Iba-1(+) major histocompatibility complex (MHC) class II(+) F4/80(+) CD11b(+) macrophages. The number of nerve-associated macrophages was greater in WT BALB/c mice than in C57BL/6J mice. There were no qualitative or quantitative differences in the circumferential distribution of nerve-associated macrophages in the cornea. Sterile corneal epithelial debridement led to a dissociation of macrophages from peripheral nerve trunks as early as 2 hours postinjury, with numbers returning to baseline after 72 hours. This dissociation was Cx3cr1 dependent. CONCLUSIONS: This study is the first to highlight a direct physical association between nerves and resident immune cells in the murine cornea. Furthermore, we reveal that this association in normal eyes is responsive to central corneal epithelial injury and is partly mediated by Cx3cr1 signaling. This association may serve as an indicator of malfunctioning neuroimmune communication in disease states such as neurotrophic keratitis and peripheral neuropathy. SN - 1552-5783 UR - https://www.unboundmedicine.com/medline/citation/24458151/A_novel_association_between_resident_tissue_macrophages_and_nerves_in_the_peripheral_stroma_of_the_murine_cornea_ DB - PRIME DP - Unbound Medicine ER -