title: Effect of macrophage migration inhibitory factor on corneal sensitivity after laser in situ keratomileusis in rabbit.
abstract: OBJECTIVE
  To investigate the effect of macrophage migration inhibitory factor (MIF) on corneal sensitivity after laser in situ keratomileusis (LASIK) surgery.
  
  
  METHODS
  New Zealand white rabbits were used in this study. A hinged corneal flap (160-µm thick) was created with a microkeratome, and -3.0 diopter excimer laser ablation was performed. Expressions of MIF mRNA in the corneal epithelial cells and surrounding inflammatory cells were analyzed using reverse transcription polymerase chain reaction at 48 hours after LASIK. After LASIK surgery, the rabbits were topically given either 1) a balanced salt solution (BSS), 2) MIF (100 ng/mL) alone, or 3) a combination of nerve growth factor (NGF, 100 ug/mL), neurotrophine-3 (NT-3, 100 ng/mL), interleukin-6 (IL-6, 5 ng/mL), and leukemia inhibitory factor (LIF, 5 ng/mL) four times a day for three days. Preoperative and postoperative corneal sensitivity at two weeks and at 10 weeks were assessed using the Cochet-Bonnet esthesiometer.
  
  
  RESULTS
  Expression of MIF mRNA was 2.5-fold upregulated in the corneal epithelium and 1.5-fold upregulated in the surrounding inflammatory cells as compared with the control eyes. Preoperative baseline corneal sensitivity was 40.56 ± 2.36 mm. At two weeks after LASIK, corneal sensitivity was 9.17 ± 5.57 mm in the BSS treated group, 21.92 ± 2.44 mm in the MIF treated group, and 22.42 ± 1.59 mm in the neuronal growth factors-treated group (MIF vs. BSS, p < 0.0001; neuronal growth factors vs. BSS, p < 0.0001; MIF vs. neuronal growth factors, p = 0.815). At 10 weeks after LASIK, corneal sensitivity was 15.00 ± 9.65, 35.00 ± 5.48, and 29.58 ± 4.31 mm respectively (MIF vs. BSS, p = 0.0001; neuronal growth factors vs. BSS, p = 0.002; MIF vs. neuronal growth factors, p = 0.192). Treatment with MIF alone could achieve as much of an effect on recovery of corneal sensation as treatment with combination of NGF, NT-3, IL-6, and LIF.
  
  
  CONCLUSIONS
  Topically administered MIF plays a significant role in the early recovery of corneal sensitivity after LASIK in the experimental animal model.
authors.affiliation: Department of Ophthalmology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
authors.forename: Joon Young
authors.initials: JY
authors.lastname: Hyon
authors.affiliation: Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Stacey
authors.initials: S
authors.lastname: Hose
authors.affiliation: CNRS UMR 5160, CRLC, Montpellier, France.
authors.forename: Celine
authors.initials: C
authors.lastname: Gongora
authors.affiliation: Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Debasish
authors.initials: D
authors.lastname: Sinha
authors.affiliation: Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Palm Beach Gardens, FL, USA.
authors.forename: Terrence
authors.initials: T
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000294:innervation / Q000502:physiology; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D020731:Keratomileusis, Laser In Situ / Q000379:methods*; D053605:Leukemia Inhibitory Factor / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000494:pharmacology*; D023421:Models, Animal; D020932:Nerve Growth Factor / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D020933:Neurotrophin 3 / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D012677:Sensation / Q000187:drug effects* / Q000502:physiology
chemical_list: D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008263:Macrophage Migration-Inhibitory Factors; D020933:Neurotrophin 3; D012333:RNA, Messenger; D020932:Nerve Growth Factor
keywords: Corneal nerve regeneration; Corneal sensitivity; Laser in situ keratomileusis; Macrophage migration-inhibitory factors