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Effect of topical fluoroquinolones on the expression of matrix metalloproteinases in the cornea.

Reviglio VE, Hakim MA, Song JK, O'Brien TP - BMC Ophthalmol (2003)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Ocular Microbiology and Immunology Laboratory, Refractive Surgery Research Laboratory, Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA. victorwilmer@aol.com

ABSTRACT

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.

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Effects of fluoroquinolone eye drops on the corneal rat's metalloproteinases expression. The bands densities of western immunoblots for MMP-1 (A) and MMP-8 (B) and zymograms for MMP-2 (C), MMP-9 (D) were subjected to densitometry analysis, the statistical significance was determined by one-way ANOVA test (values are means, error bars). P < 0.05 was considered statistically significant when compared fluoroquinolones groups vs. artificial tear group. Note the highest values of MMPs levels from topical fluoroquinolone groups compared to artificial tear group in unwounded corneas.
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Figure 4: Effects of fluoroquinolone eye drops on the corneal rat's metalloproteinases expression. The bands densities of western immunoblots for MMP-1 (A) and MMP-8 (B) and zymograms for MMP-2 (C), MMP-9 (D) were subjected to densitometry analysis, the statistical significance was determined by one-way ANOVA test (values are means, error bars). P < 0.05 was considered statistically significant when compared fluoroquinolones groups vs. artificial tear group. Note the highest values of MMPs levels from topical fluoroquinolone groups compared to artificial tear group in unwounded corneas.

Mentions: To confirm the results illustrated by immunohistochemical staining and to provide a more accurate quantitative analysis, we used western blotting and zymography techniques to study the early MMP expression after fluoroquinolone eye drop treatment. The values of each MMP bands from western blots and zymography studies made in all treated eyes were quantified by densitometry analysis and also studied statistically to indicate any significance between each fluoroquinolone treated groups and the artificial tear group (Figure 4A through 4D).


Effect of topical fluoroquinolones on the expression of matrix metalloproteinases in the cornea.

Reviglio VE, Hakim MA, Song JK, O'Brien TP - BMC Ophthalmol (2003)

Effects of fluoroquinolone eye drops on the corneal rat's metalloproteinases expression. The bands densities of western immunoblots for MMP-1 (A) and MMP-8 (B) and zymograms for MMP-2 (C), MMP-9 (D) were subjected to densitometry analysis, the statistical significance was determined by one-way ANOVA test (values are means, error bars). P < 0.05 was considered statistically significant when compared fluoroquinolones groups vs. artificial tear group. Note the highest values of MMPs levels from topical fluoroquinolone groups compared to artificial tear group in unwounded corneas.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC239861&req=5

Figure 4: Effects of fluoroquinolone eye drops on the corneal rat's metalloproteinases expression. The bands densities of western immunoblots for MMP-1 (A) and MMP-8 (B) and zymograms for MMP-2 (C), MMP-9 (D) were subjected to densitometry analysis, the statistical significance was determined by one-way ANOVA test (values are means, error bars). P < 0.05 was considered statistically significant when compared fluoroquinolones groups vs. artificial tear group. Note the highest values of MMPs levels from topical fluoroquinolone groups compared to artificial tear group in unwounded corneas.
Mentions: To confirm the results illustrated by immunohistochemical staining and to provide a more accurate quantitative analysis, we used western blotting and zymography techniques to study the early MMP expression after fluoroquinolone eye drop treatment. The values of each MMP bands from western blots and zymography studies made in all treated eyes were quantified by densitometry analysis and also studied statistically to indicate any significance between each fluoroquinolone treated groups and the artificial tear group (Figure 4A through 4D).

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Ocular Microbiology and Immunology Laboratory, Refractive Surgery Research Laboratory, Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA. victorwilmer@aol.com

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus