James T Rosenbaum1, Dongseok Choi2, David J Wilson3, Hans E Grossniklaus4, Christina A Harrington5, Roger A Dailey3, John D Ng3, Eric A Steele3, Craig N Czyz6, Jill A Foster7, David Tse8, Chris Alabiad8, Sander Dubovy8, Prashant Parekh8, Gerald J Harris9, Michael Kazim10, Payal Patel10, Valerie White11, Peter Dolman11, Deepak P Edward12, Hind Alkatan12, Hailah Al Hussain12, Dinesh Selva13, Patrick Yeatts14, Bobby Korn15, Don Kikkawa15, Patrick Stauffer3, Stephen R Planck1. 1. Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA Department of Medicine, Oregon Health & Science University, Portland, Oregon, USA Devers Eye Institute, Legacy Health Systems, Portland, Oregon, USA. 2. Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, Oregon, USA. 3. Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA. 4. Department of Ophthalmology, Emory University, Atlanta, Georgia, USA. 5. Integrated Genomics Laboratory, Oregon Health & Science University, Portland, Oregon, USA. 6. Division of Ophthalmology, Ohio University, Columbus, Ohio, USA. 7. Department of Ophthalmology, The Ohio State University, Columbus, Ohio, USA. 8. Department of Ophthalmology, University of Miami, Miami, Florida, USA. 9. Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. 10. Department of Ophthalmology, Columbia University, New York, New York, USA. 11. Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada. 12. Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. 13. Department of Ophthalmology Network, Royal Adelaide Hospital, Adelaide, South Australia, Australia. 14. Department of Ophthalmology, Wake Forest University, Winston-Salem, North Carolina, USA. 15. Department of Ophthalmology, University of California, San Diego, La Jolla, California, USA.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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