Suppression of autoimmune retinal inflammation by an antiangiogenic drug.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 23785488.
- Also identified by DOI 10.1371/journal.pone.0066219 and PMC identifier 3681944.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Angiogenesis Inhibitors
- Autoimmune Diseases
- Polyesters
- Retinitis
- Sesquiterpenes