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RPE65 Is Highly Uveitogenic in Rats

¹ From the Laboratories of Immunology and ³ Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland; the ² Department of Ophthalmology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; and the ⁴ Department of Ophthalmology, University of Florida, Gainesville, Florida.

PURPOSE. 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 µg 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.

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