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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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Typical gelatin zymography analyses of gelatinase A (MMP-2) and gelatinase B (MMP-9) expression in artificial tear group rat and in the test groups were performed. Corneal conditioned medium samples from debrided (OD) and intact (OS) corneal epithelium of each group were analyzed. 1. Tears OD; 2. Tears OS; 3. Levofloxacin 0.5% OD; 4. Levofloxacin 0.5% OS; 5. Ciprofloxacin OD; 6. Ciprofloxacin OS; 7. Ofloxacin OD; 8. Ofloxacin OS. MMP-9 (92 kDa) and MMP-2 (72 kDa) expression were up regulated in fluoroquinolone treated corneas and were present at basal level in unwounded corneas receiving artificial tears. Corneal epithelium debridement up regulated the expression of MMP-9 and MMP-2 in all test groups.
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Figure 3: Typical gelatin zymography analyses of gelatinase A (MMP-2) and gelatinase B (MMP-9) expression in artificial tear group rat and in the test groups were performed. Corneal conditioned medium samples from debrided (OD) and intact (OS) corneal epithelium of each group were analyzed. 1. Tears OD; 2. Tears OS; 3. Levofloxacin 0.5% OD; 4. Levofloxacin 0.5% OS; 5. Ciprofloxacin OD; 6. Ciprofloxacin OS; 7. Ofloxacin OD; 8. Ofloxacin OS. MMP-9 (92 kDa) and MMP-2 (72 kDa) expression were up regulated in fluoroquinolone treated corneas and were present at basal level in unwounded corneas receiving artificial tears. Corneal epithelium debridement up regulated the expression of MMP-9 and MMP-2 in all test groups.

Mentions: A comparison of topical artificial tear group as control versus groups treated with ciprofloxacin, ofloxacin and levofloxacin on the expression of corneal metalloproteinases was conducted. These studies also disclosed that the application of the present ophthalmic fluoroquinolone solutions (Ciloxan, Ocuflox and Quixin) increases MMP-1, MMP-8 (immunoblots, figure 2) and MMP-2, MMP-9 (zymography, figure 3) expression in both intact and wounded corneas although the levels of expression may be slightly different among various groups. In accordance with our previous findings, treatment with the artificial tear does not appreciably induce the expression of MMPs in intact corneal epithelium. The MMP up-regulation detected in all groups of wounded eyes presumably resulted from the wound healing process and extracellular matrix remodeling. However, the expression of MMPs in wounded eyes was up-regulated by the topical application of the fluoroquinolone drugs when compared to the artificial tear treated group. The results presented in this study demonstrated a statistically significant difference between fluoroquinolone treated groups (P < 0.0001) versus artificial tear treated group as control in the expression of corneal metalloproteinases.


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)

Typical gelatin zymography analyses of gelatinase A (MMP-2) and gelatinase B (MMP-9) expression in artificial tear group rat and in the test groups were performed. Corneal conditioned medium samples from debrided (OD) and intact (OS) corneal epithelium of each group were analyzed. 1. Tears OD; 2. Tears OS; 3. Levofloxacin 0.5% OD; 4. Levofloxacin 0.5% OS; 5. Ciprofloxacin OD; 6. Ciprofloxacin OS; 7. Ofloxacin OD; 8. Ofloxacin OS. MMP-9 (92 kDa) and MMP-2 (72 kDa) expression were up regulated in fluoroquinolone treated corneas and were present at basal level in unwounded corneas receiving artificial tears. Corneal epithelium debridement up regulated the expression of MMP-9 and MMP-2 in all test groups.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 3: Typical gelatin zymography analyses of gelatinase A (MMP-2) and gelatinase B (MMP-9) expression in artificial tear group rat and in the test groups were performed. Corneal conditioned medium samples from debrided (OD) and intact (OS) corneal epithelium of each group were analyzed. 1. Tears OD; 2. Tears OS; 3. Levofloxacin 0.5% OD; 4. Levofloxacin 0.5% OS; 5. Ciprofloxacin OD; 6. Ciprofloxacin OS; 7. Ofloxacin OD; 8. Ofloxacin OS. MMP-9 (92 kDa) and MMP-2 (72 kDa) expression were up regulated in fluoroquinolone treated corneas and were present at basal level in unwounded corneas receiving artificial tears. Corneal epithelium debridement up regulated the expression of MMP-9 and MMP-2 in all test groups.
Mentions: A comparison of topical artificial tear group as control versus groups treated with ciprofloxacin, ofloxacin and levofloxacin on the expression of corneal metalloproteinases was conducted. These studies also disclosed that the application of the present ophthalmic fluoroquinolone solutions (Ciloxan, Ocuflox and Quixin) increases MMP-1, MMP-8 (immunoblots, figure 2) and MMP-2, MMP-9 (zymography, figure 3) expression in both intact and wounded corneas although the levels of expression may be slightly different among various groups. In accordance with our previous findings, treatment with the artificial tear does not appreciably induce the expression of MMPs in intact corneal epithelium. The MMP up-regulation detected in all groups of wounded eyes presumably resulted from the wound healing process and extracellular matrix remodeling. However, the expression of MMPs in wounded eyes was up-regulated by the topical application of the fluoroquinolone drugs when compared to the artificial tear treated group. The results presented in this study demonstrated a statistically significant difference between fluoroquinolone treated groups (P < 0.0001) versus artificial tear treated group as control in the expression of corneal metalloproteinases.

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