title: Desiccating Stress-Induced MMP Production and Activity Worsens Wound Healing in Alkali-Burned Corneas.
abstract: OBJECTIVE
  To evaluate the effects of dry eye on ocular surface protease activity and sight threatening corneal complications following ocular surface chemical injury.
  
  
  METHODS
  C57BL/6 mice were subjected to unilateral alkali burn (AB) with or without concomitant dry eye for 2 or 5 days. Mice were observed daily for appearance of corneal perforation. Whole corneas were harvested and lysed for RNA extraction. Quantitative real-time PCR was performed to measure expression of inflammation cytokines, matrix metalloproteinases (MMP). Matrix metalloproteinase-9 activity, gelatinase activity, and myeloperoxidase (MPO) activity were evaluated in corneal lysates. Presence of infiltrating neutrophils was evaluated by immunohistochemistry and flow cytometry.
  
  
  RESULTS
  Eyes subjected to the combined model of AB and dry eye (CM) had 20% sterile corneal perforation rate as soon as 1 day after the initial injury, which increased to 35% by 5 days, delayed wound closure and increased corneal opacity. Increased levels of IL-1β, -6, and MMPs-1, -3, -8, -9, and -13, and chemokine (C-X-C motif) ligand 1 (CSCL1) transcripts were found after 2 days in CM compared with AB corneas. Increased MMP-1, -3, -9, and -13 immunoreactivity and gelatinolytic activity were seen in CM corneas compared with AB. Increased neutrophil infiltration and MPO activity was noted in the CM group compared with AB 2 days post injury.
  
  
  CONCLUSIONS
  Desiccating stress worsens outcome of ocular AB, creating a cytokine and protease storm with greater neutrophil infiltration, increasing the risk of corneal perforation.
authors.forename: Fang
authors.initials: F
authors.lastname: Bian
authors.forename: Flavia S A
authors.initials: FS
authors.lastname: Pelegrino
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Pflugfelder
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Volpe
authors.forename: De-Quan
authors.initials: DQ
authors.lastname: Li
authors.forename: Cintia S
authors.initials: CS
authors.lastname: de Paiva
mesh_terms: D000468:Alkalies / Q000633:toxicity; D000818:Animals; D002057:Burns, Chemical / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D005126:Eye Burns / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D012313:RNA / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014945:Wound Healing
chemical_list: D000468:Alkalies; D012313:RNA; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse