title: Fibrosis, gene expression and orbital inflammatory disease.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA Department of Public Health and Preventive Medicine, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Dongseok
authors.initials: D
authors.lastname: Choi
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Wilson
authors.affiliation: Department of Ophthalmology, Emory University, Atlanta, Georgia, USA.
authors.forename: Hans E
authors.initials: HE
authors.lastname: Grossniklaus
authors.affiliation: Integrated Genomics Laboratory, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Harrington
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Roger A
authors.initials: RA
authors.lastname: Dailey
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Ng
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Steele
authors.affiliation: Division of Ophthalmology, Ohio University, Columbus, Ohio, USA.
authors.forename: Craig N
authors.initials: CN
authors.lastname: Czyz
authors.affiliation: Department of Ophthalmology, The Ohio State University, Columbus, Ohio, USA.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Foster
authors.affiliation: Department of Ophthalmology, University of Miami, Miami, Florida, USA.
authors.forename: David
authors.initials: D
authors.lastname: Tse
authors.affiliation: Department of Ophthalmology, University of Miami, Miami, Florida, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Alabiad
authors.affiliation: Department of Ophthalmology, University of Miami, Miami, Florida, USA.
authors.forename: Sander
authors.initials: S
authors.lastname: Dubovy
authors.affiliation: Department of Ophthalmology, University of Miami, Miami, Florida, USA.
authors.forename: Prashant
authors.initials: P
authors.lastname: Parekh
authors.affiliation: Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Harris
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Kazim
authors.affiliation: Department of Ophthalmology, Columbia University, New York, New York, USA.
authors.forename: Payal
authors.initials: P
authors.lastname: Patel
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Valerie
authors.initials: V
authors.lastname: White
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Dolman
authors.affiliation: Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Deepak P
authors.initials: DP
authors.lastname: Edward
authors.affiliation: Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Hind
authors.initials: H
authors.lastname: Alkatan
authors.affiliation: Research Department, King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia.
authors.forename: Hailah
authors.initials: H
authors.lastname: Al Hussain
authors.affiliation: Department of Ophthalmology Network, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Selva
authors.affiliation: Department of Ophthalmology, Wake Forest University, Winston-Salem, North Carolina, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Yeatts
authors.affiliation: Department of Ophthalmology, University of California, San Diego, La Jolla, California, USA.
authors.forename: Bobby
authors.initials: B
authors.lastname: Korn
authors.affiliation: Department of Ophthalmology, University of California, San Diego, La Jolla, California, USA.
authors.forename: Don
authors.initials: D
authors.lastname: Kikkawa
authors.affiliation: Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Stauffer
authors.affiliation: 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.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Planck
mesh_terms: D000328:Adult; D001706:Biopsy; D005260:Female; D005355:Fibrosis / Q000235:genetics / Q000473:pathology; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007765:Lacrimal Apparatus / Q000473:pathology; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D009915:Orbit / Q000473:pathology*; D016727:Orbital Pseudotumor / Q000175:diagnosis / Q000235:genetics; D012313:RNA / Q000235:genetics*
chemical_list: D012313:RNA
keywords: Inflammation; Lacrimal gland; Orbit