Glucocorticoid receptors and inflammatory pathway gene expression in intraorbital fat and extrinsical ocular muscle in patients with Graves' orbitopathy

Abstract

Graves' orbitopathy (GO) is an auto-immune disease that occurs frequently in patients with Graves' disease and that features increased volume of extrinsical ocular musculature and orbital fat. Glucocorticoid (CG) use is efficient in many GO patients, however glucocorticoid receptors expression has not been studied at the muscular level, so far. Studies with limited number of cases showed lowered 11-beta-hidroxisteroid dehydrogenase type1 and increased expression of the active glucocorticoid receptor isoform (GR-alpha) in GO fat tissue. However, little is known about the relationship of GC-mediated inflammatory pathway (especially nuclear factor kappa-B [NF-kB] and activator protein-1) and glucocorticoid receptor expression (both GR-alpha and the competitive inhibitory form, GR-beta). In this case-control study, we will evaluate 60 patients at the ophtalmological surgery: 30 patients with GO and 30 controls - with non-tumoral indication of enucleation, allowing the collection of both muscle and fat fragments; or patients submitted to blefaroplasty, with collection of only orbital fat. We will study the mRNA expression of glucocortioid receptor alpha and beta isoforms, NF-kB, NF-kB inhibitor (NFKBIA, formerly IkBA), IkBA kinase (IKKA, recently named CHUK - conserved helix-loop-helix ubiquitous kinase), cFOS and 11²-HSD1, using real-time PCR technique. (AU)