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Fushin X Yu, Nan Gao, Haijing Sun; Hyperglycemia targets sensory nerve-dendritic cell interactions, resulting in diabetic corneal neuropathy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4706.
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To determine how the interaction of intraepithelial dendritic cells (DCs) and sensory nerve fibers/endings was disrupted by hyperglycemia and the mechanisms underlying the pathogenesis of diabetic cornea neuropathy.
C57BL/6J (B6) or CD11c-DTR mice that express a CD11c promoter-driven diphtheria toxin (DT) receptor (DTR) mice were used and diabetes was induced streptozotocin. DCs were depleted by subconjunctival injection of DT into CD11cDTR mice with wild-type B6 mice as the control. Epithelial debridement wound model was used to study sensory nerve regeneration. Whole mount immune-confocal microscopy were used to reveal DCs and sensory nerves by co-staining of CD11c and Tubulin III in the corneas.
In homeostatic corneas intraepithelial DCs and sensory nerve endings were intimately connected and in healed corneas, each innervating nerve fibers were attached to a CD11c-positive cell, suggesting a role for DC to guide epithelial innervation. Denervation resulted in rapid epithelial defects and the loss of dendriform of CD11c positive cells whereas depletion DCs decreased the density of subbasal nerve endings and delayed reinnervation in post-wounding corneas. In diabetic corneas, decrease in the density of sensory nerve ending was associated with a decrease in the number of DCs. In wounded corneas, there were numerous DCs near the leading edge of healing epithelia in both NL and DM corneas. However, there was no DCs associated with regenerating sensory nerve fibers in DM cornea. Moreover, the newly formed nerve fibers in DL corneas were evenly distributed, straight with branches, and uniform in the diameter with numerous DCs in the region whereas in DM cornea, there were less nerve fibers which were tortuous, discontinuous, or fragmented with few DCs nearby.
Our data indicate that intraepithelial DCs and sensory nerve fibers/endings are intimate connected and functionally interdependent in the cornea and during epithelial wound healing. Hyperglycemia disrupts DC-nerve interaction, resulting in diabetic peripheral neuropathy and keratopathy.
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