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Microscopic characterization of ocular damage produced by Pseudomonas aeruginosa toxin A
Abstract:
The ocular damage in young adult mice produced by purified Pseudomonas aeruginosa exotoxin A was microscopically characterized at 1 and 5 h and at 1, 3, 5, 7, 10, 14, and 21 days after toxin A challenge, using light, transmission, and scanning electron microscopic techniques. Similarly to previously described infection with viable organisms, toxin A killed both epithelial and endothelial cells and induced stromal cell swelling within 5 to 24 h after application onto the nonpenetrating wounded corneal surface. Other toxin-induced damage similar to the damage produced by infection with the viable bacteria was production of electron-dense particles within the corneal stroma, dispersal of undamaged collagen fibrils, and apparent loss of stromal proteoglycan ground substance. Toxin A damage differed from infection with the viable bacteria in essentially two ways. First, more purulent exudate and more polymorphonuclear neutrophilic leukocyte (PMN) infiltration of the corneal stroma were produced by infection with the viable organisms than by the toxin. Additionally, PMN did not appear within the toxin-treated corneas until 3 days after treatment, whereas in corneas infected with the viable organisms, PMN were numerous by 18 h. Secondly, toxin A produced cataract of the ocular lens, whereas infection with the viable organisms did not.
Insights
Pseudomonas aeruginosa exotoxin A causes ocular damage, including cell death and stromal changes, in mice. Unlike bacterial infection, exotoxin A induces cataracts but less inflammation.
Area of Science:
- Ophthalmology
- Microbiology
- Toxicology
Background:
- Pseudomonas aeruginosa is a common cause of bacterial keratitis.
- Exotoxin A (Toxin A) is a key virulence factor produced by P. aeruginosa.
Purpose of the Study:
- To microscopically characterize ocular damage caused by P. aeruginosa exotoxin A in mice.
- To compare the damage induced by exotoxin A with that caused by viable P. aeruginosa organisms.
Main Methods:
- Light, transmission, and scanning electron microscopy were used.
- Ocular damage was assessed at multiple time points after topical application of exotoxin A to wounded corneas in mice.
Main Results:
- Exotoxin A killed corneal epithelial and endothelial cells and caused stromal cell swelling.
- Damage included electron-dense particle formation, collagen fibril dispersal, and proteoglycan loss.
- Exotoxin A induced cataracts, unlike viable P. aeruginosa infection, and showed delayed polymorphonuclear neutrophilic leukocyte (PMN) infiltration.
Conclusions:
- P. aeruginosa exotoxin A causes significant ocular damage, including cell death and stromal alterations.
- Exotoxin A-induced damage differs from viable bacterial infection, notably in cataract formation and inflammatory response.
- The study highlights the specific pathological effects of exotoxin A in ocular infections.