Matrix metalloproteinase distribution during early corneal wound healing.
OBJECTIVE
To compare matrix metalloproteinase (MMP) localisation in anterior keratectomy (AK) and lamellar keratectomy (LK) wounds.


METHODS
Wounds were produced in one eye of 24 rabbits. The AK wounds were made to approximately 120 microm in depth and then allowed to re-epithelialise. The LK wounds were of similar depth, but the anterior stroma and epithelium were replaced after a second deeper keratectomy had been performed. Immunohistochemistry was used to localise the MMP-1, -2, -3, and -9 at intervals from 4 h to 14 days following surgery. The contralateral eyes acted as controls.


RESULTS
After an AK wound MMP-1 was present at the leading edge of migrating epithelium after 18 h, while MMP-2 and -9 were localised behind the advancing epithelial edge. The presence of these enzymes rapidly fell to low levels after epithelial closure. There was only faint MMP-3 localisation between days 3 and 7. After an LK wound, MMP-1, -3, and -9 were not detected in the stromal interface, but MMP-2 was present at all time points.


CONCLUSIONS
This study suggests that after an AK wound, MMP-1 is a key mediator of epithelial migration, while MMP-2 and -9, and to a lesser extent MMP-3, may participate in the remodelling of corneal stroma and the reformation of epithelial basement membrane. In contrast, an LK wound results in a much lower stimulus for MMP activation. The action of MMP-2 in stromal repair is thus partly independent of epithelial injury.
Wound Healing Research Unit, Division of Pathology, Institute of Ophthalmology, London, UK.
B
B
Mulholland
S J
SJ
Tuft
P T
PT
Khaw
D000818:Animals; D003315:Cornea / Q000201:enzymology* / Q000502:physiology; D003319:Corneal Stroma / Q000201:enzymology; D048988:Corneal Surgery, Laser; D019573:Epithelium, Corneal / Q000201:enzymology; D020731:Keratomileusis, Laser In Situ; D054018:Lasers, Excimer; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism* / Q000502:physiology; D018903:Photorefractive Keratectomy; D011184:Postoperative Period; D011817:Rabbits; D014945:Wound Healing
D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1