Effects of topical nonsteroidal antiinflammatory drugs on the expression of matrix metalloproteinases in the cornea.
OBJECTIVE
To assess the effects of nonsteroidal antiinflammatory drug (NSAID) eyedrops on the expression of matrix metalloproteinases in corneal tissue.


METHODS
Ocular Microbiology and Immunology Laboratory, Refractive Surgery Research Laboratory, The Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA.


METHODS
Seventy rats were divided into 2 groups: intact and debrided epithelium. Uniform central corneal epithelial defects were created in the right eye of the debrided corneal group. Each group was divided into 4 subgroups, each receiving 1 of the following eyedrops or artificial tears: The 3 NSAIDs were diclofenac sodium 0.1% (Falcon or Voltaren) and preservative-free ketorolac 0.5% (Acular PF). The artificial tears were carboxymethylcellulose sodium 0.5% (Refresh Plus PF). The eyedrops were administered 4 times a day for 1 week. The rats were killed on days 2 and 7. The corneas were excised and processed for immunohistochemical staining, Western blot assay, and zymography studies to determine the localization of the production of the following matrix metalloproteinases (MMPs): MMP-1, MMP-2, MMP-8, and MMP-9.


RESULTS
Matrix metalloproteinase-1, MMP-8, and MMP-2 were detected in rat corneas at 48 hours in the debrided and intact epithelium groups treated with NSAID eyedrops. The MMP-1 and MMP-8 expression levels were higher in intact corneas in the diclofenac sodium groups than in the ketorolac and artificial tears groups. The expression was localized mostly in the epithelial cells and occasionally in keratocytes.


CONCLUSIONS
This study provides preliminary evidence that topical application of some NSAIDs can induce the early expression of MMP-1, MMP-2, and MMP-8 in the cornea, suggesting that MMPs play a role in the corneal cytotoxicity of certain NSAIDs.
Reviglio
Victor E
VE
Ocular Microbiology and Immunology Laboratory, Refractive Surgery Research Laboratory, The Wilmer Eye Institute, Johns Hopkins University, Baltimore, MD 21093, USA.
Rana
Tayyib S
TS
Li
Qian J
QJ
Ashraf
M Farooq
MF
Daly
Mary K
MK
O'Brien
Terrence P
TP
D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000494:pharmacology; D003315:Cornea / Q000187:drug effects* / Q000201:enzymology / Q000601:surgery; D003646:Debridement; D004008:Diclofenac / Q000008:administration & dosage / Q000494:pharmacology*; D004847:Epithelial Cells / Q000201:enzymology; D019573:Epithelium, Corneal / Q000201:enzymology; D005260:Female; D007124:Immunoenzyme Techniques; D020910:Ketorolac / Q000008:administration & dosage / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009883:Ophthalmic Solutions; D051381:Rats; D011917:Rats, Inbred Lew; D014945:Wound Healing / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009883:Ophthalmic Solutions; D004008:Diclofenac; D020782:Matrix Metalloproteinases; D002266:Carboxymethylcellulose Sodium; D020910:Ketorolac