Purchase this article with an account.
Irene c Kuo, matias osaba, Victor e Reviglio; Fluoroquinolone pretreatment in corneal cross-linking induces stromal apoptosis. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3914.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Fluoroquinolones (FQs) can induce phototoxicity that includes necrosis, apoptosis, and loss of human lens epithelial cells. In a murine model, we investigated possible corneal phototoxicity from topical FQs instilled in eyes prior to epithelium-on corneal cross-linking by ultraviolet light (UV-CXL).
Mice were divided into groups of 16 mice each: normal untreated corneas (Group 1); UV-CXL without riboflavin or antibiotic (2); UV-CXL pretreated with moxifloxacin (3); gatifloxacin pretreatment (4); azithromycin pretreatment (5); riboflavin, no antibiotic pretreatment (6); riboflavin and moxifloxacin pretreatment (7). Topical riboflavin 0.1% was instilled. Antibiotic drops were instilled every 2 hrs for 12 hrs prior to 20 minutes of UV-light [1.4-7.3 J/ cm2 (0.7-4 mW/cm2)]. Animals were sacrificed at 24 hrs; corneas were excised and stained for apoptosis markers, matrix metalloproteinase 9 (MMP-9), and with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Polymerase chain reaction for apoptosis markers was performed, as was zymography for MMP-9. PCR for apoptosis markers and MMP-9 zymograms were quantified by scanning densitometry analysis. Comparisons were done between control and treatment groups. Spectrofluorometry was performed of dilute antibiotic concentrations (1.25 x 10-4 %).
Expression of apoptosis markers BAX, caspases 3 and 9, and MMP-9, and TUNEL staining were higher in either FQ group, in riboflavin-pretreated, and riboflavin and moxifloxacin-pretreated corneas compared with the other groups: untreated, azithromycin, and UV-CXL (ANOVA, p < 0.001) (Figure 1). The highest expression of BAX, caspases 3 and 9, and MMP-9 was in the group pretreated with riboflavin and moxifloxacin. Excitation of both FQs occurred at the wavelength used for corneal cross-linking.
In murine corneas undergoing UV-CXL, pretreatment with FQ drops induced stromal apoptosis, inflammation, and MMP-9 production; combined riboflavin and moxifloxacin pretreatment (i.e., the clinical scenario) induced the highest expression of apoptosis markers and degradative MMP-9. Fluorescence likely increases when commercially available FQ is instilled prior to UV-CXL. These findings may result from photosensitization by riboflavin and phototoxicity of FQs.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
* Denotes treatment with FQs ± riboflavin prior to UV-CXL increased expression of MMP-9, BAX, and caspases 3 and 9 compared with other groups.
This PDF is available to Subscribers Only