Role of macrophage migration inhibitory factor in corneal neovascularization.
OBJECTIVE
To determine the role of macrophage migration inhibitory factor (MIF) in inflammatory corneal neovascularization.


METHODS
Corneal neovascularization was induced by suturing 10-0 nylon 1 mm away from limbal vessel or limbal scraping after 0.15 M NaOH application in BALB/c mice. MIF expression was evaluated by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis, and immunohistochemistry. To investigate the function of MIF in inflammatory corneal neovascularization, the neovascularized area and number of infiltrating F4/80-positive cells (monocytes/macrophages) were compared between wild-type mice and homozygous MIF-deficient mice.


RESULTS
MIF mRNA and protein markedly increased in the neovascularized corneas compared with normal corneas by RT-PCR and Western blot analysis, respectively. MIF expression was upregulated immunohistochemically, not only in the corneal epithelium but also in the stromal infiltrating cells of neovascularized corneas. Neovascularized area in corneas of MIF(-/-) mice was significantly small compared with that in wild-type mice on day 7 after corneal suture and on day 14 after limbal scrape, and MIF(-/-) cornea had approximately 30% less neovascularized area than did wild-type cornea in both models. Neovascularized corneas in MIF-deficient mice had significantly fewer monocytes/macrophages than those in wild-type control mice.


CONCLUSIONS
These findings indicate that MIF, abundantly expressed in neovascularized corneas, has an angiogenic role in inflammatory corneal neovascularization and may be a therapeutic target for suppression of corneal neovascularization.
Usui
Tomohiko
T
Department of Ophthalmology, Faculty of Medicine, University of Tokyo, Tokyo Japan. tomohiko-tky@umin.ac.jp
Yamagami
Satoru
S
Kishimoto
Shuichi
S
Seiich
Yokoo
Y
Nakayama
Toshinori
T
Amano
Shiro
S
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D003315:Cornea / Q000098:blood supply* / Q000276:immunology* / Q000473:pathology; D016510:Corneal Neovascularization / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D015870:Gene Expression / Q000276:immunology; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism
D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse