The immunopathogenesis of birdshot chorioretinopathy; a bird of many feathers.

Birdshot chorioretinopathy (BSCR) is a bilateral chronic intraocular inflammation or posterior uveitis that preferentially affects middle-aged Caucasians. BSCR is characterized by distinctive multiple choroidal hypopigmented lesions in combination with retinal vasculitis and vitritis, and the extraordinary feature that virtually all patients are HLA-A29 positive. Its pathophysiology is still poorly understood. BSCR is the strongest documented association between HLA and disease in humans, which makes it an excellent model for studying the underlying immuno-genetic mechanisms of HLA class I-associated diseases. Although the association with HLA-A29 suggests that it is directly involved in the presentation of peptide antigens to T cells, the exact contribution of HLA-A29 to the pathophysiology of BSCR remains enigmatic. This article revisits the HLA-A29 peptidome using insights from recent studies and discusses why HLA-A29 can be considered a canonical antigen presenting molecule. The first genome-wide association study facilitated novel concepts into a disease mechanism beyond HLA-A29 that includes strong genetic predisposition for the ERAP2 gene that affects antigen processing for HLA class I. Furthermore, patients manifest with pro-inflammatory cytokine profiles and pathogenic T cell subsets that are associated with IL-17-linked inflammation. We are beginning to understand that the underlying biology of BSCR comprises various pathologic aspects branched into multiple molecular pathways. We propose to employ Systems Medicine to reveal their dynamic interplay for a holistic view of the immunopathology of this intriguing archetypal HLA class I-associated disease.

Effect of melatonin and zinc on the immune response in experimental Toxoplasma retinochoroiditis.

OBJECTIVES: To investigate the possible effect of melatonin (MEL) and zinc on the immune response to Toxoplasma gondii retinochoroiditis in the rat model of infection and to establish the possible value of artificial MEL and/or zinc supplementation as adjunctive therapeutic agents in the treatment of T. gondii retinochoroiditis. METHODS: Eighty-four Sprague-Dawley male rats were divided into 12 equal groups. All groups, except controls were infected with T. gondii parasite by intraperitoneal injection. Combinations of zinc-deficient diet, pinealectomy (Px), and artificial zinc and MEL were supplied during a 1-month period. At the end of the experiment, retinal and choroidal total lymphocytes, CD3+, CD4+, and CD8+ cell numbers were counted in histological sections. RESULTS: The highest amount of cellular infiltration (lymphocytes, CD3+, CD4+, CD8+ cells) in the choroid and retina was detected in infected + MEL + zinc-treated rats, and the least amount of cellular infiltration was observed in Px + zinc-deficient diet-treated rats. Although single zinc or MEL supplementation had no significant impact on the cellular infiltration in the retina and choroid in Px rats, combined therapy significantly improved these responses. CONCLUSION: Artificial supplementation of MEL and zinc should be considered as an adjunctive therapy to classic treatment of Toxoplasma retinochoroiditis especially in immunosuppressed and elderly patients if our data are confirmed in a clinical setting.