Korean J Ophthalmol.  2014 Apr;28(2):170-176. 10.3341/kjo.2014.28.2.170.

Effect of Macrophage Migration Inhibitory Factor on Corneal Sensitivity after Laser In Situ Keratomileusis in Rabbit

• Hyon JY
• Hose S
• Gongora C
• Sinha D
• O'Brien T

• KMID: 1792112
• DOI: http://doi.org/10.3341/kjo.2014.28.2.170

Abstract

PURPOSE
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-microm 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.

Keyword

Corneal nerve regeneration; Corneal sensitivity; Laser in situ keratomileusis; Macrophage migration-inhibitory factors

MeSH Terms

Animals
Epithelium, Corneal/*drug effects/innervation/physiology
Female
Humans
Interleukin-6/pharmacology
Keratomileusis, Laser In Situ/*methods
Leukemia Inhibitory Factor/pharmacology
Macrophage Migration-Inhibitory Factors/genetics/*pharmacology
Models, Animal
Nerve Growth Factor/pharmacology
Nerve Regeneration/*drug effects/physiology
Neurotrophin 3/pharmacology
RNA, Messenger/metabolism
Rabbits
Recovery of Function/*drug effects/physiology
Sensation/*drug effects/physiology
Interleukin-6
Leukemia Inhibitory Factor
Macrophage Migration-Inhibitory Factors
Nerve Growth Factor
Neurotrophin 3
RNA, Messenger

Figure

• 

  Fig. 1 Real time reverse transcription polymerase chain reaction (PCR) of migration inhibitory factor amplification from 1) cells from the superficial stromal bed of a normal rabbit eye and 2) the cells at the flap interface from the rabbit eye following laser in situ keratomileusis (LASIK) (A), 3) corneal epithelium from the control eyes and 4) corneal epithelium from the rabbit eye following LASIK (B). RNA was isolated at 48 hours after LASIK. All real time PCR values were normalized to hypoxanthine phosphoribosyl transferase as the internal control. Vertical lines represent standard deviations from the mean.

• 

  Fig. 2 Corneal sensitivity after laser in situ keratomileusis (LASIK) surgery in the rabbit eye. Preoperative baseline corneal sensitivity was 40.83 ± 2.58 mm in the balanced salt solution (BSS)-treated group, 40.00 ± 2.24 mm in the migration inhibitory factor (MIF)-treated group, and 40.83 ± 2.58 mm in the neuronal growth factors-treated group. 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. At 10 weeks after LASIK, corneal sensitivity was 15.00 ± 9.65 mm, 35.00 ± 5.48 mm, and 29.58 ± 4.31 mm, respectively. NGF = nerve growth factor; NT-3 = neurotrophine-3; IL-6 = interleukin-6; LIF = leukemia inhibitory factor. *Kruskal-Wallis test, p-value with the Bonferroni method, MIF vs. BSS, p < 0.0001; neuronal growth factors vs. BSS, p < 0.0001; †Kruskal-Wallis test, p-value with the Bonferroni method, MIF vs. BSS, p = 0.0001; neuronal growth factors vs. BSS, p = 0.002.

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