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Jose Echegaray, Michelle Senchyna, David L. Meadows, Howard A. Ketelson, Victor L. Perez; In Vivo Characterization of Corneal Inflammatory Cell Recruitment Following Exposure to Benzalkonium Chloride or Polyquad. Invest. Ophthalmol. Vis. Sci. 2012;53(14):1864.
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To determine the dose - response relationship of topically applied benzalkonium chloride (BAC) and polyquad (PQ) and the induction of a corneal inflammatory response as quantified by in vivo fluorescence stereomicroscopy.
Recruitment of inflammatory cells was monitored by in vivo fluorescent microscopy in Enhanced Green Protein Fluorescently labeled (EGFP) chimeric mice. One eye of each EGFP mouse was topically dosed with a single drop (5µL) of BAC (0.02 or 0.1%wt/%vl), PQ (0.025; 0.01 or 0.005% wt/%vl) or vehicle control (PBS). A second untreated control group was run to determine background. Drops were administered under short term anesthesia started on day 0 and occurred every two days out to day 30. In vivo recruitment of EGFP cells was captured on days between dosing and quantified from digital photos using pixel analysis (Image Pro). Corneal haze/scarring was qualitatively evaluated at the same time as EGFP quantitation.
Recruitment of EGFP labeled inflammatory cells was detected in both BAC treated groups as early as day 5 and continued to increase in magnitude over the course of the dosing period. In both groups, the magnitude of corneal EGFP infiltration correlated with the degree of corneal haze and scarring. All BAC findings were significantly different from both control groups (p-value <0.001). Although recruitment of inflammatory cells was noted with all three PQ groups, results indicated that the magnitude of recruitment was no greater that that elicited by vehicle through out the entire duration of the experiment. In addition, results from the highest PQ dose (250 ppm) were significantly lower that those seen with low dose (100 ppm) BAC.
Data demonstrate that ocular surface exposure to relatively low dose BAC induces an inflammatory response in a dose - dependent fashion with respect to both tempo and magnitude that correlates with clinical scoring. In contrast, comparatively higher concentrations of PQ do not elicit significant recruitment of inflammatory cells or haze. These results offer mechanistic insight into differences in clinical performance between PQ and BAC. These results also support the use of this model in the development of alternative preservatives for use in ophthalmic products.
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