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2005 OMIG, Abstract 9

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Topical Cholesterol as an Effective Treatment for Pneumococcus Keratitis

Mary E. Marquart, Julian M. Reed, Armando R. Caballero, Sarala Joshi, Denise C. Weathersby, Clare C. McCormick, Kathryn S. Monds, and Richard J. O'Callaghan

University of Mississippi Medical Center, Jackson, MS

Purpose: The virulence of pneumococcus keratitis has been shown to relate to the activity of pneumolysin, a potent cytotoxin. Pneumolysin binds specifically to cholesterol in host cell membranes. This study tested the effectiveness of topical cholesterol against Streptococcus pneumoniae keratitis.

Methods: The cholesterol preparation to be used in the in vivo experiments was tested for its ability to inhibit hemolysis of red blood cells by S. pneumoniae strain TIGR4 cell lysate containing pneumolysin. The corneas of New Zealand white rabbits were each injected with 105 colony-forming units (CFU) of strain TIGR4. Eyes were observed 20 and 24 hours post-infection by slit lamp examination (SLE). Immediately following each SLE, 6 eyes were treated with topical drops of 1% cholesterol in PBS containing 20% glycerol, and 7 eyes were left untreated. A final SLE was performed 48 hours post-infection, and the bacterial load in each cornea was determined by plating serial dilutions of each homogenized cornea following sacrifice.

Results: The 1% cholesterol solution effectively inhibited hemolysis by bacterial cell lysate in vitro. Prior to treatment, all of the corneas had similar SLE scores (p = 0.753). Treated and control corneas were not significantly different in SLE scores 24 hours post-infection (p = 0.403). Forty-eight hours post-infection, however, the SLE scores of the cholesterol-treated corneas (SLE = 8.146 1.23) were significantly lower than untreated corneas (SLE = 11.050 0.369; p = 0.034). Bacterial loads in the corneas were over 105 CFU per cornea for each group and were not significantly different (p = 0.472).

Conclusions: Topical cholesterol is effective in reducing the symptoms of S. pneumoniae keratitis. Cholesterol treatment is an example of a toxin receptor binding to and preventing a soluble toxin from damaging the host cell.

Disclosure Code: P

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