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Fibrosis, gene expression and orbital inflammatory disease
  1. James T Rosenbaum1,2,3,
  2. Dongseok Choi1,4,
  3. David J Wilson1,
  4. Hans E Grossniklaus5,
  5. Christina A Harrington6,
  6. Roger A Dailey1,
  7. John D Ng1,
  8. Eric A Steele1,
  9. Craig N Czyz7,
  10. Jill A Foster8,
  11. David Tse9,
  12. Chris Alabiad9,
  13. Sander Dubovy9,
  14. Prashant Parekh9,
  15. Gerald J Harris10,
  16. Michael Kazim11,
  17. Payal Patel11,
  18. Valerie White12,
  19. Peter Dolman12,
  20. Deepak P Edward13,
  21. Hind Alkatan13,
  22. Hailah al Hussain13,
  23. Dinesh Selva14,
  24. Patrick Yeatts15,
  25. Bobby Korn16,
  26. Don Kikkawa16,
  27. Patrick Stauffer1,
  28. Stephen R Planck1,2,3
  1. 1Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA
  2. 2Department of Medicine, Oregon Health & Science University, Portland, Oregon, USA
  3. 3Devers Eye Institute, Legacy Health Systems, Portland, Oregon, USA
  4. 4Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, Oregon, USA
  5. 5Department of Ophthalmology, Emory University, Atlanta, Georgia, USA
  6. 6Integrated Genomics Laboratory, Oregon Health & Science University, Portland, Oregon, USA
  7. 7Division of Ophthalmology, Ohio University, Columbus, Ohio, USA
  8. 8Department of Ophthalmology, The Ohio State University, Columbus, Ohio, USA
  9. 9Department of Ophthalmology, University of Miami, Miami, Florida, USA
  10. 10Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
  11. 11Department of Ophthalmology, Columbia University, New York, New York, USA
  12. 12Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada
  13. 13Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia
  14. 14Department of Ophthalmology Network, Royal Adelaide Hospital, Adelaide, South Australia, Australia
  15. 15Department of Ophthalmology, Wake Forest University, Winston-Salem, North Carolina, USA
  16. 16Department of Ophthalmology, University of California, San Diego, La Jolla, California, USA
  1. Correspondence to Dr James T Rosenbaum, Casey Eye Institute, Oregon Health & Science University, 3375 SW Terwilliger Blvd, Portland, OR 97239, USA; rosenbaj{at}ohsu.edu

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.

  • Orbit
  • Inflammation
  • Lacrimal gland

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