Diabetes mellitus leads to accumulation of dendritic cells and nerve fiber damage of the subbasal nerve plexus in the cornea.
PURPOSE
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.


METHODS
BALB/c mice were injected with streptozotocin (STZ) for 5 days for induction of diabetes mellitus (DM) or with vehicle solution (control). B6.VLep(ob/ob) (ob/ob) mice served as an obese and glucose-intolerant DM type 2 (DM II) model and lean B6.VLep(ob/+) (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.


RESULTS
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.


CONCLUSIONS
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.
['Leppin|Katja|K|', 'Behrendt|Ann-Kathrin|AK|', 'Reichard|Maria|M|', 'Stachs|Oliver|O|', 'Guthoff|Rudolf F|RF|', 'Baltrusch|Simone|S|', 'Eule|Johanna C|JC|', 'Vollmar|Brigitte|B|']
D000818:Animals D002452:Cell Count D003315:Cornea D003316:Corneal Diseases D003713:Dendritic Cells D003921:Diabetes Mellitus, Experimental D005260:Female D051379:Mice D008807:Mice, Inbred BALB C D018613:Microscopy, Confocal D009412:Nerve Fibers D009882:Ophthalmic Nerve
diabetes mellitus dendritic cells subbasal nerve plexus