Effect of topical fluoroquinolones on the expression of matrix metalloproteinases in the cornea.
BACKGROUND
Matrix metalloproteinases play an important role in extracellular matrix deposition and degradation. Based on previous clinical observations of corneal perforations during topical fluoroquinolone treatment, we decided to evaluate the comparative effects of various fluoroquinolone eye drops on the expression of matrix metalloproteinases (MMPs) in cornea.


METHODS
Eighty female Lewis rats were divided into two experimental groups: intact and wounded corneal epithelium. Uniform corneal epithelial defects were created in the right eye with application of 75% alcohol in the center of the tissue for 6 seconds. The treatment groups were tested as follows: 1) Tear drops: carboxymethylcellulose sodium 0.5 % (Refresh, Allergan); 2) Ciprofloxacin 0.3% (Ciloxan, Alcon); 3) Ofloxacin 0.3%(Ocuflox, Allergan); 4) Levofloxacin 0.5%(Quixin, Santen). Eye drops were administered 6 times a day for 48 hours. Rats were sacrificed at 48 hours. Immunohistochemical analysis and zymography were conducted using antibodies specific to MMPs-1, 2, 8 and 9.


RESULTS
MMP-1, MMP-2, MMP-8 and MMP-9 expression were detected at 48 hrs in undebrided corneal epithelium groups treated with the topical fluoroquinolones. No statistical difference was observed in quantitative expression of MMPs among ciprofloxacin 0.3%, ofloxacin 0.3%, levofloxacin 0.5%. When the artificial tear group and the fluoroquinolone groups with corneal epithelial defect were compared, increased expression of MMPs was observed as a result of the wound healing process. However, the fluoroquinolone treated group exhibited high statistically significantly levels of MMPs expression.


CONCLUSIONS
Our study provides preliminary evidence that topical application of fluoroquinolone drugs can induce the expression of MMP-1, MMP-2, MMP-8 and MMP-9 in the undebrided corneal epithelium compared to artificial tear eye drops.
Reviglio
Victor E
VE
Ocular Microbiology and Immunology Laboratory, Refractive Surgery Research Laboratory, Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA. victorwilmer@aol.com
Hakim
Melinda A
MA
Song
Jae K
JK
O'Brien
Terrence P
TP
D000287:Administration, Topical; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000494:pharmacology*; D003315:Cornea / Q000187:drug effects* / Q000201:enzymology; D003646:Debridement; D005260:Female; D007124:Immunoenzyme Techniques; D064704:Levofloxacin; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D015242:Ofloxacin / Q000008:administration & dosage / Q000494:pharmacology*; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew
D000890:Anti-Infective Agents; D009883:Ophthalmic Solutions; D002939:Ciprofloxacin; D064704:Levofloxacin; D015242:Ofloxacin; D020782:Matrix Metalloproteinases