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Dysregulation of CXCR3 expression on peripheral blood leukocytes in patients with neovascular age-related macular degeneration

Falk, Mads Krüger; Singh, Amardeep LU ; Faber, Carsten; Nissen, Mogens Holst; Hviid, Thomas and Sørensen, Torben Lykke (2014) In Investigative Ophthalmology & Visual Science 55(7). p.4050-4056
Abstract

PURPOSE: 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... (More)

PURPOSE: 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.

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author
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aged, Biomarkers/blood, Disease Progression, Female, Flow Cytometry, Fluorescein Angiography, Fundus Oculi, Humans, Leukocytes/metabolism, Macular Degeneration/blood, Male, Receptors, CXCR3/biosynthesis, Retinal Neovascularization/blood, Tomography, Optical Coherence
in
Investigative Ophthalmology & Visual Science
volume
55
issue
7
pages
7 pages
publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
external identifiers
  • scopus:84903997634
ISSN
1552-5783
DOI
10.1167/iovs.14-14107
language
English
LU publication?
no
id
79968016-ad1f-49f1-800f-9c071f274aa9
date added to LUP
2019-05-21 10:52:52
date last changed
2019-09-17 04:54:21
@article{79968016-ad1f-49f1-800f-9c071f274aa9,
  abstract     = {<p>PURPOSE: 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.</p><p>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.</p><p>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).</p><p>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.</p>},
  author       = {Falk, Mads Krüger and Singh, Amardeep and Faber, Carsten and Nissen, Mogens Holst and Hviid, Thomas and Sørensen, Torben Lykke},
  issn         = {1552-5783},
  keyword      = {Aged,Biomarkers/blood,Disease Progression,Female,Flow Cytometry,Fluorescein Angiography,Fundus Oculi,Humans,Leukocytes/metabolism,Macular Degeneration/blood,Male,Receptors, CXCR3/biosynthesis,Retinal Neovascularization/blood,Tomography, Optical Coherence},
  language     = {eng},
  month        = {05},
  number       = {7},
  pages        = {4050--4056},
  publisher    = {ASSOC RESEARCH VISION OPHTHALMOLOGY INC},
  series       = {Investigative Ophthalmology & Visual Science},
  title        = {Dysregulation of CXCR3 expression on peripheral blood leukocytes in patients with neovascular age-related macular degeneration},
  url          = {http://dx.doi.org/10.1167/iovs.14-14107},
  volume       = {55},
  year         = {2014},
}