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 Apr 29;55(6):3603-15. doi: 10.1167/iovs.14-14307.


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.

Keywords: dendritic cells; diabetes mellitus; subbasal nerve plexus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Cornea / innervation*
  • Cornea / pathology
  • Corneal Diseases / etiology*
  • Corneal Diseases / pathology
  • Dendritic Cells / pathology*
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / pathology*
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Confocal
  • Nerve Fibers / pathology*
  • Ophthalmic Nerve / pathology*