Molecular Genetic Advances in Uveitis

Uveitis is usually considered as an intraocular inflammation characterized by variety of clinical features. Behcet's disease (BD), Vogt-Koyanagi-Harada (VKH) syndrome, acute anterior uveitis (AAU), and birdshot chorioretinopathy (BCR) are examples of noninfectious forms of uveitis. Although the precise pathogenesis remains unclear, accumulating evidence shows that complex genetic backgrounds coupled with an aberrant immune response may be implicated in the development of uveitis. The complement and pattern recognition systems are both important factors of the innate immune system and are involved in the pathogenesis of uveitis. Copy number variants (CNVs) of complement component 4 have been found to be associated with BD and VKH syndrome, but not with AAU. Several CNVs and gene polymorphisms of toll-like receptors were found to be associated with BD. Leukocytes are an important part of the adaptive immune system and various molecules on these cells play an important role in the development of uveitis. Genes encoding for human leukocyte antigens (HLAs) have been shown to be associated with certain uveitis entities, including BD (HLA-B51), VKH syndrome (HLA-DR4, DRB1/DQA1), AAU (HLA-B27), and BCR (HLA-A29). Genome wide association studies showed that the IL-23R locus was a shared risk factor for multiple uveitis entities including BD, AAU, and VKH syndrome. In addition, various other non-HLA genes are also associated with BD or VKH syndrome, such as IL-10, STAT4, STAT3, and UBAC2. These studies support the hypothesis that genetic factors play a key role in the pathogenesis of uveitis.