Corneal wound healing is compromised by immunoproteasome deficiency

PLoS One. 2013;8(1):e54347. doi: 10.1371/journal.pone.0054347. Epub 2013 Jan 24.

Abstract

Recent studies have revealed roles for immunoproteasome in regulating cell processes essential for maintaining homeostasis and in responding to stress and injury. The current study investigates how the absence of immunoproteasome affects the corneal epithelium under normal and stressed conditions by comparing corneas from wildtype (WT) mice and those deficient in two immunoproteasome catalytic subunits (lmp7(-/-)/mecl-1(-/-), L7M1). Immunoproteasome expression was confirmed in WT epithelial cells and in cells of the immune system that were present in the cornea. More apoptotic cells were found in both corneal explant cultures and uninjured corneas of L7M1 compared to WT mice. Following mechanical debridement, L7M1 corneas displayed delayed wound healing, including delayed re-epithelialization and re-establishment of the epithelial barrier, as well as altered inflammatory cytokine production compared to WT mice. These results suggest that immunoproteasome plays an important role in corneal homeostasis and wound healing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Cornea / immunology*
  • Cornea / metabolism
  • Cornea / pathology
  • Cysteine Endopeptidases / deficiency*
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / immunology
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Debridement
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Epithelium, Corneal / immunology*
  • Epithelium, Corneal / metabolism
  • Epithelium, Corneal / pathology
  • Gene Expression
  • Homeostasis / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proteasome Endopeptidase Complex / deficiency*
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / immunology
  • Re-Epithelialization / physiology*

Substances

  • Cytokines
  • Cysteine Endopeptidases
  • LMP7 protein
  • Proteasome Endopeptidase Complex
  • Psmb10 protein, mouse