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Katja Leppin, Ann-Kathrin Behrendt, Maria Reichard, Oliver Stachs, Rudolf F. Guthoff, Simone Baltrusch, Johanna C. Eule, Brigitte Vollmar; Diabetes Mellitus Leads to Accumulation of Dendritic Cells and Nerve Fiber Damage of the Subbasal Nerve Plexus in the Cornea. Invest. Ophthalmol. Vis. Sci. 2014;55(6):3603-3615. doi: 10.1167/iovs.14-14307.
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To evaluate whether nerve fibers of the subbasal nerve plexus (SNP) and dendritic cells (DCs) are in association with each other leading to neuropathy in the diabetic cornea.
BALB/c mice were injected with streptozotocin (STZ) for 5 days for induction of diabetes mellitus (DM) or with vehicle solution (control). B6.VLepob/ob (ob/ob) mice served as an obese and glucose-intolerant DM type 2 (DM II) model and lean B6.VLepob/+ (ob/+) mice as respective controls. Using in vivo corneal confocal microscopy (CCM), nerve fibers and DCs were quantified over a period of 9 weeks and additionally analyzed by in vitro immunofluorescence whole-mount staining.
In STZ-diabetic mice, CCM revealed an increase of DC density (DCD) in contrast to controls, whereas nerve fiber density (NFD) was decreased with duration of DM. In ob/ob mice, DCD was 3-fold higher than in both ob/+ mice and STZ-diabetic mice. Whole-mount staining displayed CD11c(+) and major histocompatibility complex (MHC) class II(+) mature DCs in colocalization with class III β-tubulin(+) nerve fibers in the cornea.
Hyperglycemia leads to corneal DC infiltration, and obesity aggravates this immune response. The direct contact between DCs and the SNP can be assumed to be a trigger of nerve fiber damage and thus a contributing factor to polyneuropathy in diabetic corneas.
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