RPE65 is highly uveitogenic in rats.
OBJECTIVE
To examine the hypothesis that RPE65, a protein specific to the retinal pigment epithelium, is uveitogenic in rats.


METHODS
Rats of four inbred strains (Lewis, Brown Norway, Fischer, and SHR) were immunized with native or recombinant bovine RPE65, or with S-antigen (S-Ag), emulsified with complete Freund adjuvant, and treated simultaneously with killed Bordetella pertussis bacteria, as indicated. Development of ocular changes was examined and scored both clinically and histologically.


RESULTS
Lewis rats immunized with RPE65 showed development of acute and severe inflammatory eye disease that affected most ocular tissues. The minimum uveitogenic dose of RPE65 was similar to that of S-Ag (1 microg per rat), but the changes induced by RPE65 at higher dose ranges were less severe than those induced by S-Ag. Concurrent treatment of the RPE65-immunized rats with B. pertussis bacteria was not critical for disease induction, but enhanced dramatically the pathogenic reaction. Unlike the results with several other retinal proteins, no pinealitis was detected in rats immunized with RPE65. Fischer (F344) rats resembled Lewis rats in being similarly affected by RPE65 or S-Ag. In contrast, Brown Norway (BN) rats developed severe disease when immunized with RPE65, but showed minimal changes in response to S-Ag. SHR rats responded poorly to disease induced by RPE65, and S-Ag-induced disease failed to develop.


CONCLUSIONS
RPE65 is highly uveitogenic in rats, thus suggesting that this molecule could be involved in pathogenic autoimmunity in the human eye.
Ham
Don-Il
DI
Laboratory of Immunology, National Eye Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 10N112, Bethesda, MD 20892-1857, USA.
Gentleman
Susan
S
Chan
Chi-Chao
CC
McDowell
J Hugh
JH
Redmond
T Michael
TM
Gery
Igal
I
D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000473:pathology; D002352:Carrier Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D005136:Eye Proteins / Q000302:isolation & purification / Q000633:toxicity*; D007114:Immunization; D008297:Male; D010857:Pigment Epithelium of Eye / Q000737:chemistry*; D011506:Proteins / Q000302:isolation & purification / Q000633:toxicity*; D051381:Rats; D011914:Rats, Inbred BN; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011918:Rats, Inbred SHR; D011994:Recombinant Proteins; D014605:Uveitis / Q000139:chemically induced* / Q000473:pathology; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D002352:Carrier Proteins; D005136:Eye Proteins; D011506:Proteins; D011994:Recombinant Proteins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase