Abstract
Purpose: :
Alpha-toxin is a known mediator of corneal damage and is suspected to cause damage in other ocular sites. This study analyzed the direct effects of alpha-toxin in the anterior chamber and the ability of chemical inhibits to limit such damage.
Methods: :
Aqueous humor (~50ul) was removed from the anterior chambers of rabbits prior to injection of 25 hemolytic units of alpha-toxin in 10ul of phosphate buffered saline (PBS) (n ≥ 4 eyes per group). Alpha-toxin injected eyes were then treated by injection (50ul) of one of two inhibitors of alpha-toxin (modified cyclodextrin or cyclodextrin:cholesterol complex; 1% in PBS). Eyes were photographed and evaluated for pathology by slit lamp examination (SLE) scoring at 2, 3, 4 and 5 hours post-injection (PI). Animals were euthanized and whole eyes excised, fixed, embedded, and sectioned for microscopic histological analysis.
Results: :
Eyes injected with alpha-toxin alone had a maximum SLE score (~8.12) at 5 hours PI. Toxin injected eyes treated with the modified cyclodextrin produced a significantly lower (p = 0.0003) SLE score of 2.94±0.45 by 5 hours PI compared to eyes with alpha-toxin alone. Eyes treated with the cyclodextrin:cholesterol complex also had significantly lower (p ≤ 0.0058) SLE scores of 4.47±0.51 compared to controls.Analysis of histological sections of eyes injected with alpha-toxin alone demonstrated dialation of the iris vasculature, and edema of the iris and ciliary process, as well as damage and sloughing of the corneal endothelium and iris pigmented epithelium. Histological sections of eyes injected with alpha-toxin and treated with either inhibitor revealed no marked pathological changes.
Conclusions: :
Alpha-toxin is capable of causing significant direct damage to the anterior chamber. This pathological damage can be prevented by alpha-toxin inhibitors such as modified cyclodextrin or a cyclodextrin:cholesterol complex.
Keywords: anterior chamber • Staphylococcus • microbial pathogenesis: experimental studies