Abstract
Purpose: :
Define and analyze age–related changes in susceptibility to experimental keratitis
Methods: :
Intrastromal injections of 100 colony–forming units (CFU) of S. aureus strain 8325–4 were used to induce keratitis in young (8 – 10 weeks) and aged (approximately 36 months) New Zealand white rabbits (n = 6 corneas per group). Purified staphylococcal alpha–toxin (0.37 µg; 25.6 hemolytic units) was intrastromally injected into corneas of both young and aged rabbits (n = 6 corneas per group). Pathology was scored by two masked observers based on gross and slit–lamp examinations at 15, 20, and 25 hours post–infection, and at 1 and 3 hours following injection of toxin. Additionally, alpha–toxin–mediated hemolytic assays were performed using erythrocytes obtained from young and aged rabbits.
Results: :
Slit–lamp examinations of pathology due to S. aureus keratitis produced scores significantly lower in aged than in young animals at 15, 20, and 25 hours post–infection (P ≤ 0.001). Log CFU’s were not significantly different between young and aged animals at the time of sacrifice (25 hours post–infection; P = 0.896). Intrastromal injection of purified alpha–toxin demonstrated significantly more pathology in young, as compared to aged, rabbit corneas (P ≤ 0.0005). Hemolysis assays revealed that erythrocytes of young rabbits were four–fold more susceptible to the action of staphylococcal alpha–toxin than those of their aged counterparts.
Conclusions: :
Corneas and erythrocytes of aged rabbits, relative to those of young rabbits, were significantly less susceptible to S. aureus keratitis and to alpha–toxin; this difference likely being mediated by decreased response to the action of alpha–toxin.
Keywords: aging • keratitis • Staphylococcus