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

TY - JOUR

T1 - Dysregulation of CXCR3 expression on peripheral blood leukocytes in patients with neovascular age-related macular degeneration

AU - Falk, Mads Krüger

AU - Singh, Amardeep

AU - Faber, Carsten

AU - Nissen, Mogens H

AU - Hviid, Thomas

AU - Sørensen, Torben Lykke

PY - 2014/5/8

Y1 - 2014/5/8

N2 - 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+ CXCR3high 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.

AB - 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+ CXCR3high 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.

U2 - 10.1167/iovs.14-14107

DO - 10.1167/iovs.14-14107

M3 - Journal article

C2 - 24812555

SN - 0146-0404

VL - 55

SP - 4050

EP - 4056

JO - Investigative Ophthalmology & Visual Science

JF - Investigative Ophthalmology & Visual Science

IS - 7

ER -