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Stephen R Planck, Dongseok Choi, Christina A. Harrington, David J Wilson, Hans E Grossniklaus, Patrick Stauffer, James T Rosenbaum, Orbital Inflammatory Disease Consortium; Fibrosis, Gene Expression, and Orbital Inflammatory Disease. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3425.
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© ARVO (1962-2015); The Authors (2016-present)
Fibrosis is an important association with inflammation that affects the orbital tissue. To clarify the pathogenesis of fibrosis in orbital diseases, we analyzed the gene expression in orbital biopsies and compared our results to those reported for idiopathic pulmonary fibrosis.
We collected 153 biopsies including 68 from the lacrimal gland and 85 from orbital fat. Diagnoses included healthy controls (n=27), nonspecific orbital inflammation (NSOI) (n=64), thyroid eye disease (TED) (n=33), sarcoidosis (n=20), and granulomatosis with polyangiitis (GPA) (n=9). Fibrosis was scored on a zero to three scale by two expert, ophthalmic pathologists. Gene expression was quantified using Affymetrix U133 plus 2.0 microarray.
Within orbital fat, fibrosis was greatest among subjects with GPA (2.75±0.46) and significantly increased in tissue from subjects with GPA, NSOI, or sarcoid (p<0.01), but not for TED, compared to controls (1.13±0.69). For the lacrimal gland, the average fibrosis score among healthy controls (1.36±0.48) did not differ statistically from any of the 4 disease groups. 73 probe sets identified transcripts (~54 genes) correlating with fibrosis in orbital fat (false discovery rate < 0.05 and fold-difference >1.5). Transcripts with increased expression included fibronectin, lumican, thrombospondin, and collagen types I and VIII. Many of these transcripts were also increased in pulmonary fibrosis.
A pathologist’s recognition of fibrosis in orbital tissue correlates well with increased expression of transcripts considered essential in fibrosis. Furthermore, overlapping genes have been detected in pulmonary fibrosis. The study supports the accuracy of histological scoring of fibrosis and conversely, the results help to validate gene expression analysis from formalin-fixed tissue as an accurate methodology to understand pathophysiology.
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