In vitro effects of aminoglycosides and fluoroquinolones on keratocytes.
OBJECTIVE
Commonly used fluoroquinolones are reported to have less of an effect than aminoglycosides on corneal epithelial cells. The purpose of this study was to assess the effects of these antibiotics on stromal keratocytes in vitro.


METHODS
Cultured rabbit keratocytes were incubated with various concentrations of gentamicin, tobramycin, ofloxacin, norfloxacin, and ciprofloxacin. Evaluations were performed by means of phase-contrast microscopy and [3H]thymidine uptake assay after 24 hours and 48 hours of incubation with the drug (concentrations from 3 to 0.003 mg/ml).


RESULTS
At a concentration of 3 mg/ml, all three fluoroquinolones inhibited keratocyte proliferation significantly more than either aminoglycoside after 24 hours (P<0.001) and after 48 hours (P<0.001). In contrast to the aminoglycosides, all three fluoroquinolones induced a dose- dependent inhibition of proliferation after 24 hours. Even at the lowest concentration (0.003 mg/ml), ofloxacin and norfloxacin inhibited keratocyte proliferation significantly (P=0.001) compared to control after 24 hours. Concentrations of fluoroquinolones ranging from 0.09 to 0.24 mg/ml produced a 50% inhibition of proliferation, a level of inhibition not observed with any tested concentration of aminoglycosides. After 24 hours, all three fluoroquinolones, but neither of the aminoglycosides, showed moderate to severe signs of cytotoxicity at a concentration of 3 mg/ml.


CONCLUSIONS
Relative effects of fluoroquinolones and aminoglycosides on epithelial cells and stromal keratocytes appear to be different. This might have an impact on choosing the optimal antibiotic drug to be applied prophylactically in clinical situations in which the epithelium is absent, such as after photorefractive keratectomy or chemical burn.
Seitz
B
B
Doheny Eye Institute, University of Southern California School of Medicine, Los Angeles, CA 90033, USA.
Hayashi
S
S
Wee
W R
WR
LaBree
L
L
McDonnell
P J
PJ
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology / Q000187:drug effects; D003319:Corneal Stroma / Q000166:cytology / Q000187:drug effects*; D004247:DNA / Q000096:biosynthesis; D004261:DNA Replication / Q000187:drug effects; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D024841:Fluoroquinolones; D008858:Microscopy, Phase-Contrast; D011817:Rabbits; D013936:Thymidine / Q000378:metabolism
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D004247:DNA; D013936:Thymidine