Diabetes mellitus leads to accumulation of dendritic cells and nerve fiber damage of the subbasal nerve plexus in the cornea.
OBJECTIVE
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.
Institute for Experimental Surgery, University of Rostock, Rostock, Germany.
Katja
K
Leppin
Institute for Experimental Surgery, University of Rostock, Rostock, Germany.
Ann-Kathrin
AK
Behrendt
Department of Ophthalmology, University of Rostock, Rostock, Germany.
Maria
M
Reichard
Department of Ophthalmology, University of Rostock, Rostock, Germany.
Oliver
O
Stachs
Department of Ophthalmology, University of Rostock, Rostock, Germany.
Rudolf F
RF
Guthoff
Institute of Medical Biochemistry and Molecular Biology, University of Rostock, Rostock, Germany.
Simone
S
Baltrusch
Small Animal Clinic, Faculty of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
Johanna C
JC
Eule
Institute for Experimental Surgery, University of Rostock, Rostock, Germany.
Brigitte
B
Vollmar
D000818:Animals; D002452:Cell Count; D003315:Cornea / Q000294:innervation* / Q000473:pathology; D003316:Corneal Diseases / Q000209:etiology* / Q000473:pathology; D003713:Dendritic Cells / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D009412:Nerve Fibers / Q000473:pathology*; D009882:Ophthalmic Nerve / Q000473:pathology*
dendritic cells; diabetes mellitus; subbasal nerve plexus