Anti-rat ICAM-1 antibody does not influence the course of experimental melanin-induced uveitis.
OBJECTIVE
Experimental melanin-induced uveitis (EMIU) is a T cell-mediated rat model of acute anterior uveitis. We investigated the possibility of preventing the inflammation with monoclonal antibody directed against rat intercellular adhesion molecule 1 (ICAM-1).


METHODS
To induce EMIU, Lewis rats were immunized with bovine ocular melanin extract (250-500 microg). Each day from day 6 post-immunization, rats were injected intraperitoneally with anti-ICAM-1 monoclonal antibody (IA29) or normal mouse serum, and examined with a slit-lamp biomicroscope. On the first day of clinical inflammation, intravital microscopy of iris vasculature was performed on each animal following intraperitoneal injection of rhodamine 6G. At the peak of clinical inflammation, rats were killed, and eyes were examined histologically. Binding potency of IA29 was tested by flow cytometry using concanavalin A-stimulated rat T cells. Immunohistochemical staining was used to detect IA29 on rat uveal vascular endothelium.


RESULTS
The ability of IA29 to bind T cell blasts was present to a 1:2000 dilution, and IA29 was readily detectable on uveal vascular endothelium following systemic administration. However, there was no significant difference (p > 0.05) in incidence, time of onset, or severity or histological appearance of EMIU for the rats treated with IA29 when compared with the control rats. Intravital microscopy revealed sticking of leukocytes in the iris vasculature in both groups.


CONCLUSIONS
We were unable to demonstrate an inhibitory effect of anti-rat ICAM-1 antibody on the outcome of EMIU. Our observations may reflect a redundancy in the adhesion molecule profile responsible for this uveitis.
Smith
J R
JR
Casey Eye Institute, Oregon Health Sciences University, Portland, Oregon 97201-4197, USA. smithjus@ohsu.edu
O'Rourke
L M
LM
Becker
M D
MD
Cao
M
M
Williams
K A
KA
Planck
S R
SR
Rosenbaum
J T
JT
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007124:Immunoenzyme Techniques; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007498:Iris / Q000098:blood supply; D008297:Male; D008543:Melanins; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000378:metabolism; D014606:Uveitis, Anterior / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
D000911:Antibodies, Monoclonal; D008543:Melanins; D018799:Intercellular Adhesion Molecule-1