title: TSG-6 protects corneal endothelium from transcorneal cryoinjury in rabbits.
abstract: OBJECTIVE
  To investigate the effect of an anti-inflammatory protein, TNF-α stimulated gene/protein (TSG)-6 and an antiapoptotic protein, stanniocalcin (STC)-1 on corneal endothelium in rabbits with transcorneal cryoinjury.
  
  
  METHODS
  Transcorneal freezing (-80°C) was applied to rabbit corneas for 30 seconds. Immediately post injury, either TSG-6 (10 μg/100 μL), STC-1 (10 μg/100 μL), or the same volume of balanced salt solution (BSS) was injected into the anterior chamber. Each eye was examined for corneal opacity, corneal thickness, endothelial cell density, and endothelial hexagonality every 2 to 6 hours for 48 hours post injury. The concentrations of myeloperoxidase (MPO) and IL-1β were measured in the aqueous humor every 6 hours. At 48 hours post injury, each cornea was assayed for TNF-α, IL-1β, IL-6, and MPO, and histologically evaluated with alizarin red-trypan blue staining, hematoxylin-eosin staining, and immunostaining for neutrophils.
  
  
  RESULTS
  Tumor necrosis factor-α stimulated gene/protein-6 significantly decreased the development of corneal opacity and edema after cryoinjury compared with STC-1 or BSS. The corneal endothelial cell density and hexagonality were markedly preserved by TSG-6. The mRNA levels of TNF-α, IL-1β, and IL-6 in the cornea and the protein levels of MPO and IL-1β in the aqueous humor and cornea were significantly lower in TSG-6-treated eyes than BSS-treated controls. Similarly, the expression of fibroblast growth factor-2 was reduced by TSG-6 treatment. Histologic evaluation demonstrated that neutrophil infiltration of the cornea was decreased in TSG-6-treated eyes.
  
  
  CONCLUSIONS
  Tumor necrosis factor-α stimulated gene/protein-6 protected corneal endothelial cells from transcorneal cryoinjury through suppression of inflammation.
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Jongno-gu, Seoul, Korea.
authors.forename: Jeong-Ah
authors.initials: JA
authors.lastname: Kim
authors.affiliation: Laboratory for Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Jongno-gu, Seoul, Korea.
authors.forename: Jung Hwa
authors.initials: JH
authors.lastname: Ko
authors.affiliation: Laboratory for Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Jongno-gu, Seoul, Korea.
authors.forename: Ah Young
authors.initials: AY
authors.lastname: Ko
authors.affiliation: Laboratory for Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Jongno-gu, Seoul, Korea.
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Jongno-gu, Seoul, Korea Laboratory for Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Jongno-gu, Seoul, Korea.
authors.forename: Mee Kum
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Jongno-gu, Seoul, Korea Laboratory for Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Jongno-gu, Seoul, Korea.
authors.forename: Won Ryang
authors.initials: WR
authors.lastname: Wee
authors.affiliation: Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine at Scott & White, Temple, Texas, United States.
authors.forename: Ryang Hwa
authors.initials: RH
authors.lastname: Lee
authors.affiliation: Department of Surgery, Ophthalmology Section, Central Texas Veterans Health Care System, Temple, Texas, United States.
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Fulcher
authors.affiliation: Department of Ophthalmology, Seoul National University Hospital, Jongno-gu, Seoul, Korea Laboratory for Ocular Regenerative Medicine and Immunology, Biomedical Research Institute, Seoul National University Hospital, Jongno-gu, Seoul, Korea.
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Oh
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000494:pharmacology*; D002452:Cell Count; D003318:Corneal Opacity / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D004728:Endothelium, Corneal / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005131:Eye Injuries / Q000150:complications* / Q000473:pathology / Q000628:therapy; D005615:Freezing / Q000009:adverse effects; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015815:Cell Adhesion Molecules; C072273:TNFAIP6 protein, human; D014409:Tumor Necrosis Factor-alpha
keywords: TSG-6; corneal endothelial cell; inflammation