Fibrosis, gene expression and orbital inflammatory disease

• Type of Material: Article
• Authors: James T. Rosenbaum, Oregon Health and Science University; Dongseok Choi, Oregon Health and Science University; David J. Wilson, Oregon Health and Science University; Hans Grossniklaus, Emory University; Christina A. Harrington, Oregon Health and Science University; Roger A. Dailey, Oregon Health and Science University; John D. Ng, Oregon Health and Science University; Eric A. Steele, Oregon Health and Science University; Craig N. Czyz, Ohio University; Jill A. Foster, Ohio State University; David Tse, University of Miami; Chris Alabiad, University of Miami; Sander Dubovy, University of Miami; Prashant Parekh, University of Miami; Gerald J. Harris, Medical College of Wisconsin; Michael Kazim, Columbia University; Payal Patel, Columbia University; Valerie White, University of British Columbia; Peter Dolman, University of British Columbia; Deepak P. Edward, King Khaled Eye Specialist Hospital; Hind Alkatan, King Khaled Eye Specialist Hospital; Hailah al Hussain, King Khaled Eye Specialist Hospital; Dinesh Selva, Royal Adelaide Hospital; Patrick Yeatts, Wake Forest University; Bobby Korn, University of California, San Diego; Don Kikkawa, University of California San Diego; Patrick Stauffer, Oregon Health and Science University; Stephen R. Planck, Oregon Health and Science University
• Language: English
• Date: 2015-10-01
• Publisher: BMJ Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015, British Medical Journal Publishing Group.
• Final Published Version (URL): http://dx.doi.org/10.1136/bjophthalmol-2015-306614
• Title of Journal or Parent Work: British Journal of Ophthalmology
• ISSN: 0007-1161
• Volume: 99
• Issue: 10
• Start Page: 1424
• End Page: 1429
• Grant/Funding Information: NIH Grants EY020249, EY010572 and RR024140, Research to Prevent Blindness, the William and Mary Bauman Foundation, the Mas Family Foundation, and the Stan and Madelle Rosenfeld Family Trust.
• Keywords: orbital inflammation; lacrimal gland; Science & Technology; fibrosis; gene expression; Life Sciences & Biomedicine; Ophthalmology
• Research Categories: Health Sciences, Pathology; Health Sciences, Opthamology

Abstract

Background/Aims: To clarify the pathogenesis of fibrosis in inflammatory orbital diseases, we analysed the gene expression in orbital biopsies and compared our Results: with those reported for idiopathic pulmonary fibrosis. Methods: We collected 140 biopsies from 138 patients (58 lacrimal glands; 82 orbital fat). Diagnoses included healthy controls (n=27), non-specific orbital inflammation (NSOI) (n=61), thyroid eye disease (TED) (n=29), sarcoidosis (n=14) and granulomatosis with polyangiitis (GPA) (n=7). Fibrosis was scored on a 0-3 scale by two experts, ophthalmic pathologists. Gene expression was quantified using Affymetrix U133 plus 2.0 microarray. Results: 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 sarcoidosis ( p<0.01), but not for TED, compared with healthy controls (1.13±0.69). For lacrimal gland, the average score among controls (1.36±0.48) did not differ statistically from any of the four disease groups. Seventy three probe sets identified transcripts correlating with fibrosis in orbital fat (false discovery rate <0.05) after accounting for batch effects, disease type, age and sex. Transcripts with increased expression included fibronectin, lumican, thrombospondin and collagen types I and VIII, each of which has been reported upregulated in pulmonary fibrosis. Conclusions: A pathologist's recognition of fibrosis in orbital tissue correlates well with increased expression of transcripts that are considered essential in fibrosis. Many transcripts implicated in orbital fibrosis have been previously implicated in pulmonary fibrosis. TED differs from other causes of orbital fat inflammation because fibrosis is not a major component. Marked fibrosis is less common in the lacrimal gland compared with orbital adipose tissue.