Suppression of Autoimmune Retinal Inflammation by an Antiangiogenic Drug |
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| Authors: | Takeru Yoshimura Ofra Benny Lauren Bazinet Robert J D’Amato |
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| Institution: | 1. Department of Surgery, Vascular Biology Program, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.; 2. Department of Ophthalmology, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.; New York University, United States of America, |
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| Abstract: | Chronic and recurrent uveitis account for approximately 10% of legal blindness in the western world. Autoimmune uveitis is driven by activated CD4+ T cells that differentiate into effector T helper cells (Th1, Th2, and Th17) which release proinflammatory cytokines that damage the retina. In this study we investigated the effect of the methionine aminopeptidase 2 (MetAP2) inhibitor, Lodamin, on T cell activation and differentiation. MetAp2 is an enzyme which regulates cellular protein synthesis and is highly expressed in T cells. Lodamin was found to suppress T cell receptor (TCR) mediated T cell proliferation and reduced the production of Th1 and Th17 cells. Further, Lodamin suppressed overall inflammation in the mouse model of experimental autoimmune uveitis (EAU) by a six fold. This effect was attributed in part to a reduction in retinal proinflammatory cytokines, down regulation of MetAP2 expression in purified lymph node CD4+ T cells, and a general normalization of the systemic immune reaction. |
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