Pathological aspects of spontaneous uveitis and retinopathy in HLA-A29 transgenic mice and in animal models of retinal autoimmunity: relevance to human pathologies.

摘要

PURPOSE: 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. MATERIALS AND 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. CONCLUSION: 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.