Anny M S Cheng1, Han Y Yin2, Angus Chen3, Ya-Wen Liu4, Mei-Chun Chuang4, Hua He1, Sean Tighe1, Hosam Sheha1, Shu-Lang Liao5. 1. Ocular Surface Center, Miami, Florida, United States. 2. Florida International University Herbert Wertheim College of Medicine, Miami, Florida, United States. 3. School of Medicine, National Taiwan University, Taipei, Taiwan. 4. Institute of Molecular Medicine, National Taiwan University, Taipei, Taiwan. 5. School of Medicine, National Taiwan University, Taipei, Taiwan 5Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.
Abstract
PURPOSE: To investigate the role of extraocular muscles (EOM) myoblasts in Graves ophthalmopathy (GO) pathology and the effect of a cyclooxygenase (COX)-2 inhibitor and a peroxisome proliferator-activated receptor (PPAR)-γ agonist in its treatment. METHODS: Myoblasts were isolated and cultured from EOM of 10 patients with GO and 4 without (non-GO). The cultured myoblasts were treated with IFN-γ, insulin-like growth factor (IGF)-1, IL-1β, and TNF-α, and the effect on PPAR-γ, COX-2, TGF-β, and thyroid stimulating hormone receptor (TSH-R) expressions were assessed using real-time (RT)-PCR, ELISA, and Western blot. The effect of a COX-2 inhibitor and a PPAR-γ agonist on the expression of TGF-β, hyaluronan synthases (HAS)-1, -2, and -3, and hyaluronan (HA) were further evaluated. RESULTS: Real-time PCR showed significant upregulation in PPAR-γ, COX-2, TGF-β, and TSH-R mRNA expression in GO myoblasts when treated with TNF-α but not in the non-GO. While IFN-γ and IGF-1 had no significant effect, IL-1β did upregulate COX-2 expression. These results were further confirmed by ELISA and Western blotting. Tumor necrosis factor α-induced TGF-β in turn significantly increased HA expression and HAS3 level, but not HAS1 and HAS2. The cyclooxygenase 2 inhibitor and PPAR-γ agonist substantially diminished this TNF-α-induced TGF-β, HA, and HAS3 expression. CONCLUSIONS: These results demonstrate the role of EOM myoblasts in the pathogenesis of GO. The cyclooxygenase 2 inhibitor and PPAR-γ agonist in this study are potential treatments for GO due to their ability to suppress TNF-α-induced TGF-β, HAS, and HA upregulation.
PURPOSE: To investigate the role of extraocular muscles (EOM) myoblasts in Graves ophthalmopathy (GO) pathology and the effect of a cyclooxygenase (COX)-2 inhibitor and a peroxisome proliferator-activated receptor (PPAR)-γ agonist in its treatment. METHODS: Myoblasts were isolated and cultured from EOM of 10 patients with GO and 4 without (non-GO). The cultured myoblasts were treated with IFN-γ, insulin-like growth factor (IGF)-1, IL-1β, and TNF-α, and the effect on PPAR-γ, COX-2, TGF-β, and thyroid stimulating hormone receptor (TSH-R) expressions were assessed using real-time (RT)-PCR, ELISA, and Western blot. The effect of a COX-2 inhibitor and a PPAR-γ agonist on the expression of TGF-β, hyaluronan synthases (HAS)-1, -2, and -3, and hyaluronan (HA) were further evaluated. RESULTS: Real-time PCR showed significant upregulation in PPAR-γ, COX-2, TGF-β, and TSH-R mRNA expression in GO myoblasts when treated with TNF-α but not in the non-GO. While IFN-γ and IGF-1 had no significant effect, IL-1β did upregulate COX-2 expression. These results were further confirmed by ELISA and Western blotting. Tumor necrosis factor α-induced TGF-β in turn significantly increased HA expression and HAS3 level, but not HAS1 and HAS2. The cyclooxygenase 2 inhibitor and PPAR-γ agonist substantially diminished this TNF-α-induced TGF-β, HA, and HAS3 expression. CONCLUSIONS: These results demonstrate the role of EOM myoblasts in the pathogenesis of GO. The cyclooxygenase 2 inhibitor and PPAR-γ agonist in this study are potential treatments for GO due to their ability to suppress TNF-α-induced TGF-β, HAS, and HA upregulation.
Authors: Vardaan Gupta; Christine L Hammond; Elisa Roztocil; Mithra O Gonzalez; Steven E Feldon; Collynn F Woeller Journal: Surv Ophthalmol Date: 2021-09-04 Impact factor: 6.197
Authors: Catherine J Choi; Wensi Tao; Ravi Doddapaneni; Zenith Acosta-Torres; Nathan W Blessing; Bradford W Lee; Daniel Pelaez; Sara T Wester Journal: Invest Ophthalmol Vis Sci Date: 2018-12-03 Impact factor: 4.799