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

Abstract

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.

• Authors: Yvonne de Kozak, Serge Camelo, Marika Pla
• Journal: Ophthalmic research (Ophthalmic Res) Vol. 40 Issue 3-4 Pg. 175-80 ( 2008) ISSN: 1423-0259 [Electronic] Switzerland
• PMID: 18421235 (Publication Type: Comparative Study, Journal Article)
• Copyright: 2008 S. Karger AG, Basel.

Chemical References

• HLA-A Antigens
• HLA-A29 antigen
• beta 2-Microglobulin

Topics

• Animals
• Autoimmune Diseases (immunology, pathology)
• Autoimmunity (immunology)
• Disease Models, Animal
• Disease Progression
• Female
• Follow-Up Studies
• HLA-A Antigens (immunology)
• Humans
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Rats
• Rats, Inbred Lew
• Retina (immunology)
• Severity of Illness Index
• Uveitis (immunology, pathology)
• beta 2-Microglobulin (immunology)