Experimental autoimmune uveitis induced by immunization with retinal pigment epithelium-specific 65-kDa protein peptides.
OBJECTIVE
To investigate the pathogenic potential and sites of retinal pigment epithelium-specific 65-kDa protein (RPE65) for inducing experimental autoimmune uveitis (EAU) in Lewis rats.


METHODS
Twenty-six peptides were chemically synthesized based on the amino acid sequences of human RPE65. These peptides spanned the entire RPE65 sequence. Each peptide was injected into a footpad and the peritoneum of Lewis rats. The eyes were examined by slit-lamp biomicroscopy, and the findings were correlated with the histological findings. The serum antibody titer and lymphocyte reactivity against each peptide was also determined by enzyme-liked immunosorbent assay (ELISA) and lymphocyte proliferation assay, respectively.


RESULTS
Active immunization of rats resulted in the induction of EAU with 14 (3 severe and 11 mild) of the 26 peptides. The clinical course of the EAU was similar to that induced by the injection of retinal antigens such as S-antigen or inter-photoreceptor retinoid binding protein (IRBP). However, the histopathologic changes differed from the EAU induced by these retinal antigens. The inflammation was induced mainly from the retinal pigment epithelium (RPE) and the choroid, while the retina was relatively well-preserved except for some granulomatous changes adjacent to the RPE.


CONCLUSIONS
Active immunization with peptides making up RPE65 will induce EAU. RPE65 has multiple EAU-inducing sites for Lewis rats.
Nakamura
Hideo
H
Department of Ophthalmology, Akita University School of Medicine, Hondo, Akita City, Japan.
Yamaki
Kunihiko
K
Kondo
Isao
I
Sakuragi
Shozo
S
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D002352:Carrier Proteins; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000276:immunology*; D016056:Immunodominant Epitopes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008970:Molecular Weight; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology*; D010857:Pigment Epithelium of Eye / Q000737:chemistry / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D015866:Uveitis, Posterior / Q000276:immunology* / Q000473:pathology; D014611:Vaccination; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D002352:Carrier Proteins; D005136:Eye Proteins; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase