Corneal wound healing is compromised by immunoproteasome deficiency.
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.
Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, United States of America.
Deborah A
DA
Ferrington
Heidi
H
Roehrich
Angela A
AA
Chang
Craig W
CW
Huang
Marcela
M
Maldonado
Wendy
W
Bratten
Abrar A
AA
Rageh
Neal D
ND
Heuss
Dale S
DS
Gregerson
Elizabeth F
EF
Nelson
Ching
C
Yuan
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D003315:Cornea / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D003546:Cysteine Endopeptidases / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003646:Debridement; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019573:Epithelium, Corneal / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006706:Homeostasis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046988:Proteasome Endopeptidase Complex / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D062326:Re-Epithelialization / Q000502:physiology*
D016207:Cytokines; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex; C490920:Psmb10 protein, mouse