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Patrick Lee, Nan Gao, Fushin X Yu; CD11c-Positive Dendritic Cells Mediate Epithelium-Innervation and Guide Sensory Nerve Regeneration Post Epithelium-Wounding in the Cornea. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):729.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate mechanisms underlying epithelium innervation in homeostatic corneas and re-innervation in post-wound corneas.
Cornea were wounded by debridement and allowed to heal in vivo. Dendritic cells were depleted locally in the cornea by using the diphtheria toxin (DT)-mediated depletion of DCs in B6-CD11c-DTR mice. SiRNAs for gene knockdown were subconjunctivally injected prior to epithelium-wounding. Sensory nerve fibers/endings and dendritic cells were assessed by whole mount confocal microscopy.
Two morphologically differing dendritic cells were detected: dendriform and round-shaped. Dendriform DCs were in intimate contact with sub-basal nerve endings while the round-shaped DCs were located at the branch points of nerve fibers that innervated the epithelium. 3-D reconstruction showed that CD11c-positive cells accompanied sensory nerve fibers to cross the corneal epithelium basal lamina. Depletion of DCs resulted in reduced nerve ending density and delayed post-wound re-innervation. Finally, epithelium-expressed class 3 semaphorins were found to be important guidance molecules for sensory nerve regeneration in the cornea.
DCs and neurons are functionally interdependent and morphologically interconnected. DCs mediate epithelium-innervation and guide sensory nerve regeneration post epithelium-wounding.
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