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(Investigative Ophthalmology and Visual Science. 2008;49:1367-1375.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-1007
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Corneal Wound Healing in an Osteopontin-Deficient Mouse

Ken-ichi Miyazaki,1 Yuka Okada,1 Osamu Yamanaka,1 Ai Kitano,1 Kazuo Ikeda,2 Shigeyuki Kon,3 Toshimitsu Uede,3 Susan R. Rittling,4,5 David T. Denhardt,4,5 Winston Whei-Yang Kao,6 and Shizuya Saika1

1From the Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan; 2Department of Anatomy, Graduate School of Medicine, Osaka City University, Osaka, Japan; 3Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan; 4Departments of Genetics and Cell Biology and 5Neuroscience, Rutgers University, Piscataway, New Jersey; and 6Department of Ophthalmology, University of Cincinnati Medical Center, Cincinnati, Ohio.

PURPOSE. To investigate the effects of loss of osteopontin (OPN) in the healing of the injured cornea in mice. Cell culture study was also conducted to clarify the effects of OPN in fibroblast behaviors.

METHODS. Ocular fibroblasts from wild-type (WT) and OPN-null (KO) mice were used to study the role of OPN on cell behavior. The effect of the lack of OPN on corneal wound healing was evaluated in mice.

RESULTS. In cell culture, OPN is involved in cell adhesion and in the migration of ocular fibroblasts. Adhesion of the corneal epithelial cell line was not affected by exogenous OPN. OPN was upregulated in a healing, injured mouse cornea. Loss of OPN did not affect epithelial healing after simple epithelial debridement. Healing of an incision injury in cornea was delayed, with less appearance of myofibroblasts and transforming growth factor β1 expression in a KO mouse than in a WT mouse. The absence of OPN promoted tissue destruction after an alkali burn, resulting in a higher incidence of corneal perforation in KO mice than in WT mice.

CONCLUSIONS. OPN modulates wound healing-related fibroblast behavior and is required to restore the physiological structure of the cornea after wound healing.






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Copyright © 2008 by the Association for Research in Vision and Ophthalmology