title: Dendritic cell dysfunction and diabetic sensory neuropathy in the cornea.
abstract: Diabetic peripheral neuropathy (DPN) often leads to neurotrophic ulcerations in the cornea and skin; however, the underlying cellular mechanisms of this complication are poorly understood. Here, we used post-wound corneal sensory degeneration and regeneration as a model and tested the hypothesis that diabetes adversely affects DC populations and infiltration, resulting in disrupted DC-nerve communication and DPN. In streptozotocin-induced type 1 diabetic mice, there was a substantial reduction in sensory nerve density and the number of intraepithelial DCs in unwounded (UW) corneas. In wounded corneas, diabetes markedly delayed sensory nerve regeneration and reduced the number of infiltrating DCs, which were a major source of ciliary neurotrophic factor (CNTF) in the cornea. While CNTF neutralization retarded reinnervation in normal corneas, exogenous CNTF accelerated nerve regeneration in the wounded corneas of diabetic mice and healthy animals, in which DCs had been locally depleted. Moreover, blockade of the CNTF-specific receptor CNTFRα induced sensory nerve degeneration and retarded regeneration in normal corneas. Soluble CNTFRα also partially restored the branching of diabetes-suppressed sensory nerve endings and regeneration in the diabetic corneas. Collectively, our data show that DCs mediate sensory nerve innervation and regeneration through CNTF and that diabetes reduces DC populations in UW and wounded corneas, resulting in decreased CNTF and impaired sensory nerve innervation and regeneration.
authors.forename: Nan
authors.initials: N
authors.lastname: Gao
authors.forename: Chenxi
authors.initials: C
authors.lastname: Yan
authors.forename: Patrick
authors.initials: P
authors.lastname: Lee
authors.forename: Haijing
authors.initials: H
authors.lastname: Sun
authors.forename: Fu-Shin
authors.initials: FS
authors.lastname: Yu
mesh_terms: D000818:Animals; D020934:Ciliary Neurotrophic Factor / Q000276:immunology; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit / Q000276:immunology; D003315:Cornea / Q000276:immunology* / Q000294:innervation* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000276:immunology* / Q000473:pathology; D051379:Mice; D011984:Sensory Receptor Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D020934:Ciliary Neurotrophic Factor; D053739:Ciliary Neurotrophic Factor Receptor alpha Subunit