Pathological aspects of spontaneous uveitis and retinopathy in HLA-A29 transgenic mice and in animal models of retinal autoimmunity: relevance to human pathologies.
OBJECTIVE
A major increased risk of developing birdshot chorioretinopathy is reported in humans who are HLA-A29-positive. To better characterize this disease, an animal model of HLA-A29-associated disease was developed and the pathology arising spontaneously in these transgenic mice was compared to animal models of autoimmune uveoretinitis and to human pathology.


METHODS
HLA-A2902 cDNA (A29c) was obtained from a patient suffering from birdshot retinochoroidopathy and used for transgene construct to generate HLA-A29 transgenic mice. Histopathological examination of the animal cohort was performed up to 15 months of age. It was compared with the ocular pathology developed in C57BL/6 mice and in Lewis rats immunized with retinal autoantigens.


RESULTS
Aging HLA-A29 transgenic mice spontaneously developed an ocular disease with resemblance to experimental retinal-Ag-induced autoimmune ocular disease and to human pathologies shown in birdshot retinochoroidopathy, Vogt-Koyanagi-Harada and sympathetic ophthalmia. Pathogenic mechanisms could possibly be shared by these conditions.


CONCLUSIONS
Humanized models of ocular inflammation developed in HLA class I and class II transgenic mice will help better understand the mechanisms responsible for ocular inflammation. Local control of autoimmunity in HLA-A29-positive individuals would be an important option for new therapeutic strategies.
de Kozak
Yvonne
Y
Institut National de la Santé et de la Recherche Médicale U872, Paris, France. ydekozak@ccr.jussieu.fr
Camelo
Serge
S
Pla
Marika
M
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology*; D015551:Autoimmunity / Q000276:immunology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D015234:HLA-A Antigens / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D051381:Rats; D011917:Rats, Inbred Lew; D012160:Retina / Q000276:immunology*; D012720:Severity of Illness Index; D014605:Uveitis / Q000276:immunology / Q000473:pathology*; D001613:beta 2-Microglobulin / Q000276:immunology
D015234:HLA-A Antigens; C035524:HLA-A29 antigen; D001613:beta 2-Microglobulin