title: Dysregulation of CXCR3 expression on peripheral blood leukocytes in patients with neovascular age-related macular degeneration.
abstract: OBJECTIVE
  The chemokine receptor CXCR3 has been strongly related to inhibition of angiogenesis. The purpose of this study was to investigate the association between expression of CXCR3 on peripheral blood leukocytes and age-related wet macular degeneration. Furthermore, we measured the plasma concentration of chemokines CXCL9 to -11.
  
  
  METHODS
  The study group consisted of patients with age-related macular degeneration (AMD) attending our department. Patients referred for reasons other than AMD were enrolled as control subjects. The expression of CXCR3 on T cells and the plasma concentration of CXCL9 to -11 were measured using flow cytometry.
  
  
  RESULTS
  We looked at all CD8(+) T cells expressing CXCR3 and found a significantly lower percentage of these cells in the neovascular AMD group compared to the age-matched control group (P = 0.05). When dividing the CD8(+) cells into functional groups according to their expression of CXCR3, we found a significantly lower percentage of CD8(+) CXCR3(high) cells in the group with neovascular AMD compared to the control group (P = 0.038). We found a lower percentage of CD4(+)CD69(+)CXCR3(+) T cells in the group of patients with neovascular AMD when compared to the age-matched control group (P = 0.052).
  
  
  CONCLUSIONS
  Our results point toward a systemic dysregulation of CXCR3 in patients with neovascular AMD. Since there is evidence to suggest that CXCR3 is able to alter the response of VEGF, the primary driver of choroidal neovascularization (CNV) formation, low levels of CXCR3 could potentially drive some patients toward a more angiogenic profile leading to CNV formation and growth. CXCR3-enhancing molecules could therefore be a possible target for treatment of AMD.
authors.affiliation: Clinical Eye Research Unit, Department of Ophthalmology, Copenhagen University Hospital Roskilde, Roskilde, Denmark, and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mads Krüger
authors.initials: MK
authors.lastname: Falk
authors.affiliation: Clinical Eye Research Unit, Department of Ophthalmology, Copenhagen University Hospital Roskilde, Roskilde, Denmark, and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Amardeep
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Microbiology, Immunology and International Health, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Faber
authors.affiliation: Department of Microbiology, Immunology and International Health, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mogens Holst
authors.initials: MH
authors.lastname: Nissen
authors.affiliation: Department of Clinical Biochemistry, Centre for Immune Regulation and Reproductive Immunology, Copenhagen University Hospital Roskilde, Roskilde, Denmark, and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hviid
authors.affiliation: Clinical Eye Research Unit, Department of Ophthalmology, Copenhagen University Hospital Roskilde, Roskilde, Denmark, and Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Torben Lykke
authors.initials: TL
authors.lastname: Sørensen
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008268:Macular Degeneration / Q000097:blood* / Q000473:pathology; D008297:Male; D054367:Receptors, CXCR3 / Q000096:biosynthesis*; D015861:Retinal Neovascularization / Q000097:blood* / Q000473:pathology; D041623:Tomography, Optical Coherence
chemical_list: D015415:Biomarkers; C515187:CXCR3 protein, human; D054367:Receptors, CXCR3
keywords: AMD; VEGF; chemokines; neovascularization