title: The ocular surface of glaucoma patients treated over the long term expresses inflammatory markers related to both T-helper 1 and T-helper 2 pathways.
abstract: OBJECTIVE
  To investigate the expression of CCR5 and CCR4, two chemokine receptors, as markers of the T helper (Th) 1 and Th2 pathways, respectively, and class II antigen HLA-DR as a hallmark of inflammation on conjunctival cells obtained from patients receiving long-term glaucoma treatment.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  A total of 18 normal subjects and 70 glaucoma patients treated with topical antiglaucoma drugs for more than 1 year: 14 receiving a beta-blocker as monotherapy, 38 treated with a prostaglandin analog alone (19 with latanoprost, 6 with travoprost, 13 with bimatoprost), and 18 receiving multiple treatments.
  
  
  METHODS
  Impression cytologic specimens (ICSs) were obtained from 1 eye of the patients and processed for flow cytometry. Conjunctival cells were extracted and incubated with monoclonal antibodies against CCR4, CCR5, HLA-DR, or their specific controls to measure, in a masked manner, the percentages of conjunctival cells positive for the 3 markers.
  
  
  METHODS
  HLA-DR and chemokine receptors (CCR4 and CCR5) in ICSs.
  
  
  RESULTS
  Compared with all other groups, HLA-DR expression was raised significantly in the multitreatment group, whereas all monotherapies showed slight and nonsignificant increases. Both CCR4 and CCR5 were increased significantly in all 5 glaucoma groups compared with normal subjects, with no between-group differences.
  
  
  CONCLUSIONS
  This study demonstrates the overexpression of 2 chemokine receptors in the conjunctival epithelium of glaucoma patients treated over the long term. These results show the simultaneous overexpression of CCR4 and CCR5, suggesting that the chronic use of topical treatments may stimulate both the Th1 and Th2 systems simultaneously. These results also suggest that inflammatory mechanisms combining allergy with toxicity are at work and illustrate the complexity of inflammatory reactions occurring in the ocular surface of glaucoma patients.
authors.affiliation: Department of Ophthalmology, Quinze-Vingts National Ophthalmology Hospital and Ambroise Paré Hospital, APHP, Paris-Ouest School of Medicine, University of Versailles, Versailles, France. baudouin@quinze-vingts.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Baudouin
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
authors.forename: Pascale
authors.initials: P
authors.lastname: Hamard
authors.forename: Luisa
authors.initials: L
authors.lastname: Riancho
authors.forename: Catherine
authors.initials: C
authors.lastname: Creuzot-Garcher
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Warnet
authors.forename: Françoise
authors.initials: F
authors.lastname: Brignole-Baudouin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D002908:Chronic Disease; D003228:Conjunctiva / Q000166:cytology; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D019085:Fluorescent Antibody Technique, Direct; D005902:Glaucoma, Open-Angle / Q000188:drug therapy* / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D054398:Receptors, CCR4 / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D006684:HLA-DR Antigens; D054398:Receptors, CCR4; D019713:Receptors, CCR5