Use of polymyxin as an endotoxin blocker in the prevention of diffuse lamellar keratitis in an animal model.
OBJECTIVE
To determine whether bacterial endotoxin, lipopolysaccharide (LPS), could induce diffuse lamellar keratitis (DLK) in an animal model and whether DLK could be prevented by endotoxin blockers such as polymyxin.


METHODS
Laser in situ keratomileusis (LASIK) flaps were created in rabbit eyes. The stromal bed was treated with 20 microg of Burkholderia cepacia LPS or balanced salt solution (BSS). Development of DLK, histological degree of inflammation, and presence of LPS detected by anti-LPS antibody were evaluated after 48 hours. In a second experiment, all eyes received LPS and were randomly assigned to receive either polymyxin in the form of two drops of Polytrim (Allergan, Irvine, Calif) on the stromal bed or two drops of BSS.


RESULTS
In the animal model study, LPS was significantly associated with the development of DLK (P<.05, n=30). Infiltration with polymorphonuclear cells and presence of DLK were found in LPS treated eyes but not in controls. In the second experiment, 4 (27%) of 15 eyes that received polymyxin in addition to LPS developed DLK compared to 18 (95%) of 19 eyes that received only LPS (P<.05, n=34). There was a trend towards higher flap displacement in polymyxin treated eyes but this was not significant (P=.07).


CONCLUSIONS
Diffuse lamellar keratitis in a rabbit model can be caused by bacterial endotoxin (LPS). Endotoxin blockers, such as polymyxin, are effective in decreasing the incidence of endotoxin-induced DLK in a rabbit model.
Morck
Douglas W
DW
Life and Environmental Sciences, Animal Resource Centre, University of Calgary, Calgary, Alberta, Canada.
Holland
Simon P
SP
Ceri
Howard
H
Hancock
Robert
R
Scott-Gough
Monisha
M
Nugyen
Van
V
Keith
Erin J
EJ
Lee
Tracy L
TL
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D019121:Burkholderia Infections / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D016956:Burkholderia cepacia; D003315:Cornea / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015818:Eye Infections, Bacterial / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007634:Keratitis / Q000382:microbiology / Q000473:pathology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000633:toxicity*; D009883:Ophthalmic Solutions; D011112:Polymyxin B / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D011897:Random Allocation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D009883:Ophthalmic Solutions; D014409:Tumor Necrosis Factor-alpha; D011112:Polymyxin B