title: Dry eye syndrome in thyroid-associated ophthalmopathy: lacrimal expression of TSH receptor suggests involvement of TSHR-specific autoantibodies.
abstract: OBJECTIVE
  We evaluated the relationship between ocular surface damage, elevated lid aperture/impaired Bell's phenomenon and reduced tear production in thyroid-associated ophthalmopathy (TAO). Suspecting a possible role of autoantibodies specific for TSH receptor (TSHR), we further investigated TSHR expression in the healthy lacrimal gland (LG).
  
  
  METHODS
  A total of 48 patients with active TAO and 26 controls were examined for basal tear secretion, Rose Bengal and fluorescein staining, impression cytology (IPC), break-up time (BUT), and blinking (lid width, lid closure, ocular surface, upward excursion). Healthy LGs were investigated immunohistochemically for expression of TSHR.
  
  
  RESULTS
  Thyroid-associated ophthalmopathy patients showed significant ocular surface damage (Rose Bengal staining score: TAO: 2.0 [0-5] versus controls: 0 [0-0.4]; IPC score: TAO 3.0 [0-8] versus controls: 0 [0-1], and BUT: TAO: 3.0 seconds [0-9 seconds] versus controls: 19.5 seconds [13-35.4 seconds]), and significantly reduced tear secretion (TAO: 10 mm [3-20 mm] versus controls: 17 mm [10-27 mm]). Ocular surface damage correlated significantly with tear secretion (r = - 0.35) but not significantly with mechanical alterations (impaired upgaze [r = - 0.34] and ocular surface increase [r = 0.32]). We firstly demonstrate that lacrimal acinar cells physiologically express TSHR.
  
  
  CONCLUSIONS
  As ocular surface damage in TAO significantly correlates with reduced tear production, LG impairment appears to be a major cause of ocular surface drying. Intriguingly, physiological expression of TSHR by LG suggests that, in thyroid disease, autoantibodies may bind to lacrimal TSHR and, perhaps via aberrant signal transduction, contribute to LG impairment and, hence, dry eye syndrome.
authors.affiliation: Department of Ophthalmology, Essen University Hospital, Germany. anja.eckstein@uni-essen.de
authors.forename: Anja K
authors.initials: AK
authors.lastname: Eckstein
authors.forename: Andreas
authors.initials: A
authors.lastname: Finkenrath
authors.forename: Arnd
authors.initials: A
authors.lastname: Heiligenhaus
authors.forename: Katrin
authors.initials: K
authors.lastname: Renzing-Köhler
authors.forename: Joachim
authors.initials: J
authors.lastname: Esser
authors.forename: Carsten
authors.initials: C
authors.lastname: Krüger
authors.forename: Beate
authors.initials: B
authors.lastname: Quadbeck
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Steuhl
authors.forename: Robert K
authors.initials: RK
authors.lastname: Gieseler
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000378:metabolism*; D001324:Autoantigens / Q000378:metabolism*; D001767:Blinking; D015352:Dry Eye Syndromes / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005456:Fluorescent Dyes; D006111:Graves Disease / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007765:Lacrimal Apparatus / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011989:Receptors, Thyrotropin / Q000276:immunology*; D012395:Rose Bengal; D013666:Tears / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D005456:Fluorescent Dyes; D011989:Receptors, Thyrotropin; D012395:Rose Bengal