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Daniel G. Ezra, Geoffrey E. Rose, Maryse Bailly; Genome Level Microarray Expression Profiling Implicates IGF-1 And Wnt Signalling Dysregulation In The Pathogenesis Of Thyroid Associated Ophthalmopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5100. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
The pathogenesis of thyroid associated ophthalmopathy (TAO) remains unclear. The purpose of this study is to elucidate the gene expression profile of orbital fat in untreated TAO.
This study was conducted at the Moorfields and UCL Institute of Ophthalmology NIHR Biomedical Research Centre for Ophthalmology, London, UK. 5 test samples of orbital fat from TAO patients and 4 control orbital fat specimens were identified from the pathology library at the UCL Institute of Ophthalmology, UCL, London. None of the patients had received any previous treatments for TAO. RNA extraction was performed using the Qiagen Rneasy extraction kit according to manufacturers protocols. cDNA Expression analysis was performed using a GeneChip® Human Genome U133 Plus 2.0 Affymetrix genome level cDNA microarray platform. The Human Genome U133 Plus 2.0 platform covers expression of over 47,000 transcripts and variants including 38,500 characterised human genes, providing expression analysis of an extremely wide range of potential genes. Expression data was normalised using a Robust Multiarray Average analysis. ANOVA was used to compare normalised gene expression levels.
The highest ranked gene expression differences identified were dominated by IGF-1 signalling genes, including: IGF-1 and IGFBP6; IGF1-R binding/signalling genes such as SOCS3 and IRS2 (cytoplasmic signalling molecules binding to IGF-1R); and also downstream signalling and transcriptional regulators such as SGK (PDK/Akt signalling) and c-JUN. Our microarray data also confirms Wnt signalling gene dysregulation including wnt5a, sFRPs, dkk and WIF1.
Altered Wnt signalling confirms confirming previous array findings. Further investigation of the role of Wnt signalling in TAO pathogenesis warranted. These data also provide the first evidence of dysregulation of IGF-1 pathway genes in TAO tissue, further strengthening the evidence for the role of IGF-1 signalling in the pathogenesis and potential treatment of TAO.
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