Expression of matrix metalloproteinases 2 and 9 in experimental corneal injury and fungal keratitis.
OBJECTIVE
Levels of matrix metalloproteinases (MMPs) can be modulated during corneal infection, but little is known about MMP profiles during fungal keratitis. The purpose of this study was to determine the effect of corneal trauma and immunosuppressive treatment on the expression kinetics of MMP-2 and MMP-9 during experimental keratomycosis.


METHODS
Corneas of immunocompetent and cyclophosphamide-treated adult BALB/c mice were topically inoculated with 1 x 10 culturable units of Fusarium solani or mock-inoculated with or without superficial corneal scarification. Eyes were scored daily for disease severity and processed for zymography after 1.5 hours, 6 hours, 1 day, 4 days, or 8 days. Gelatinase activity was densitometrically quantitated and normalized to MMP-2 and MMP-9 controls.


RESULTS
MMP-9 levels in nontraumatized eyes transiently increased at 6 hours after fungal exposure, but this increase was inhibited by cyclophosphamide treatment. Corneal injury significantly induced early MMP-9 expression that returned to baseline levels within 4 days. Cyclophosphamide pretreatment reduced and delayed MMP-9 after scarification. Fusarium exposure dampened the MMP-9 response to corneal trauma in immunocompetent and cyclophosphamide-treated animals. Ocular levels of MMP-2 were not affected by scarification, fungal exposure, or immunosuppressive treatment.


CONCLUSIONS
Ocular MMP-9 levels, but not MMP-2 levels, increased soon after corneal injury. A similar, although muted, MMP-9 response occurs during early filamentous fungal keratitis, with a kinetic profile similar to corneal disease progression. The early stage of ulcerative keratitis may involve selective regulation of corneal matrix metalloproteinases, suggesting an initial opportunity for therapeutic intervention.
Mitchell
Bradley M
BM
Sid W. Richardson Ocular Microbiology Laboratory, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, TX 77030, USA. bmm@bcm.tmc.edu
Wu
Tzu G
TG
Chong
Eva-Marie
EM
Pate
J Carey
JC
Wilhelmus
Kirk R
KR
D000818:Animals; D065306:Corneal Injuries; D003320:Corneal Ulcer / Q000188:drug therapy / Q000201:enzymology* / Q000382:microbiology; D003520:Cyclophosphamide / Q000627:therapeutic use; D004195:Disease Models, Animal; D015821:Eye Infections, Fungal / Q000188:drug therapy / Q000201:enzymology / Q000382:microbiology; D005131:Eye Injuries / Q000188:drug therapy / Q000201:enzymology* / Q000382:microbiology; D005260:Female; D005670:Fusarium / Q000254:growth & development / Q000472:pathogenicity*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009181:Mycoses / Q000188:drug therapy / Q000201:enzymology* / Q000382:microbiology; D014949:Wounds, Nonpenetrating / Q000188:drug therapy / Q000201:enzymology / Q000382:microbiology
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9