Graves ophthalmopathy: low-dose glucocorticoid increases peroxisome proliferator-activated receptor-gamma gene expression Oftalmopatia de Graves: dose baixa de glicorticoide aumenta a expressão gênica do peroxisome proliferator-activated receptor gamma

Dear Editor: In the study of the pathophysiology for Graves ophthalmopathy (GO), a growing interest has been demonstrated in the role of nuclear receptors related to adipocyte differentiation (1) , with an emphasis on peroxisome proliferator-activated receptor-gamma (PPAR-γ) (2) . Another point of concern has been the inflammatory response, a result of the release by monocytes and macrophages of cytokines and other mediators, which can contribute significantly to the progression of the condition and implies that corticotherapy should be the main therapeutic approach (3) . Unlike what happens in the adipocyte pathway, PPAR-g activation has been associated with inhibition of the inflammatory process induced by certain cytokines (4) , which raises doubts about the final balance of receptor stimulation regarding the evolution of GO. Furthermore, the possible relation of PPAR-g with the treatment of an ocular condition with glucocorticoids remain to be clarified. Here, we have reported our experience with PPAR-g gene expression, observed in orbital fibroblast cultures from a patient with GO, in the presence of different glucocorticoid dosages. It was a white female patient, 62 years old, who had been diagnosed with Graves disease (GD) for 11 years, and was currently using methima zole (30 mg/day). She presented with inactive GO (Clinical Active Score (CAS): 2), with moderate to severe ocular involvement (3) and with bilateral proptosis (exophthalmometer reading of 24 mm and 23 mm in right and left eyes, respectively), and without strabismus or optic neuropathy. Computed tomography showed only bilateral ocular proptosis. Patient underwent orbital decompression surgery at the Clinics Hospital (CH) of the Botucatu Medical School (FMB)-Unesp. She was, at the time of the surgery, clinically controlled from the thyrotoxicosis, with serum free thyroxin levels of 1.64 ng/dL (reference ranges: 0.8-1.9 ng/dL) and thyrotropin (TSH) of 0.20 µIU/mL (reference ranges: 0.4-4.0 µIU/mL). The fibroconjunctive material extracted from the orbital space during surgery was seeded on 199 media, with bovine fetal serum (Gibco®) and antibiotic/antimycotic solution (Sigma®); the fibroblasts resultant from this initial procedure were cultured until confluence of approximately 80%. Next they were submitted to treatment with either 10 nM or 100 nM of dexamethasone, in biological triplicate, compared for PPAR-g gene expression, and evaluated through real time polymerase chain reaction (real time-PCR) with non-treated fibroblasts. The treatments were compared using two-factor analysis of variance (ANOVA), complemented with Tukey’s multiple comparison test. The value of p<0.05 was considered statistically significant. The fibroblasts presented a 65% greater PPAR-g gene expression on the cells treated with 10 nM of dexamethasone compared to those not treated. The fibroblasts treated with 100 nM of dexamethasone did not differ in PPAR- g gene expression from those who received 10nM and from those not treated (Figure 1). Thus, considering the importance of the PPAR-g receptor to the adipocyte