PURPOSE: Chemokine signaling and monocytes/macrophages were implicated in the pathogenesis of AMD. We tested the association between chemokines involved in monocyte recruitment and AMD. METHODS: Immunophenotyping for white blood cell (WBC) populations including CD14++CD16- and CD14+CD16+ monocytes, CD19+, CD3+, and CD16+ lymphocytes, and chemokine receptors CCR1, CCR2, CCR5, CX(3)CR1, and CXCR4 was performed on peripheral blood from treatment-naïve neovascular AMD (NV-AMD) patients and controls. The mRNA level of chemokine receptors in monocytes was measured with quantitative-PCR. Systemic levels of major chemokine ligands CCL2, CCL5, CCL3, and CXCL10 were evaluated by ELISA. Genotyping was performed for risk SNPs for AMD in the CFH, C3, and HTRA1 genes. RESULTS: The percentage of WBC subpopulations tested was similar between NV-AMD patients (n = 18) and controls (n = 20). CD14+CD16+ monocyte subpopulation showed a 3.5-fold increased expression of CCR1 (P = 0.039; t-test) and a 2.2-fold increased expression of CCR2 (P = 0.027) in patients compared with controls. Increased CCR1 and CCR2 expression was correlated with each other in patients (R(2) = 0.64, P < 0.0001), but not controls (R(2) = 0.02, P = 0.57). Increased mRNA levels of CCR1 (1.6-fold, P = 0.037) and CCR2 (1.6-fold, P = 0.007) were found in monocytes from NV-AMD patients. Chemokine receptor expression was not correlated with the presence of risk SNPs, and was not associated with blood chemokine levels. CONCLUSIONS: CCR1 and CCR2 are coupregulated on the CD14+CD16+ monocyte population in NV-AMD patients. These data implicate CD14+CD16+ monocytes and chemokine signaling in AMD. Additional investigation is needed to elucidate the role of these monocytes and their potential as a biomarker or therapeutic target for AMD.
PURPOSE: Chemokine signaling and monocytes/macrophages were implicated in the pathogenesis of AMD. We tested the association between chemokines involved in monocyte recruitment and AMD. METHODS: Immunophenotyping for white blood cell (WBC) populations including CD14++CD16- and CD14+CD16+ monocytes, CD19+, CD3+, and CD16+ lymphocytes, and chemokine receptors CCR1, CCR2, CCR5, CX(3)CR1, and CXCR4 was performed on peripheral blood from treatment-naïve neovascular AMD (NV-AMD) patients and controls. The mRNA level of chemokine receptors in monocytes was measured with quantitative-PCR. Systemic levels of major chemokine ligands CCL2, CCL5, CCL3, and CXCL10 were evaluated by ELISA. Genotyping was performed for risk SNPs for AMD in the CFH, C3, and HTRA1 genes. RESULTS: The percentage of WBC subpopulations tested was similar between NV-AMDpatients (n = 18) and controls (n = 20). CD14+CD16+ monocyte subpopulation showed a 3.5-fold increased expression of CCR1 (P = 0.039; t-test) and a 2.2-fold increased expression of CCR2 (P = 0.027) in patients compared with controls. Increased CCR1 and CCR2 expression was correlated with each other in patients (R(2) = 0.64, P < 0.0001), but not controls (R(2) = 0.02, P = 0.57). Increased mRNA levels of CCR1 (1.6-fold, P = 0.037) and CCR2 (1.6-fold, P = 0.007) were found in monocytes from NV-AMDpatients. Chemokine receptor expression was not correlated with the presence of risk SNPs, and was not associated with blood chemokine levels. CONCLUSIONS:CCR1 and CCR2 are coupregulated on the CD14+CD16+ monocyte population in NV-AMDpatients. These data implicate CD14+CD16+ monocytes and chemokine signaling in AMD. Additional investigation is needed to elucidate the role of these monocytes and their potential as a biomarker or therapeutic target for AMD.
Authors: Jeroen Bastiaans; Jan C van Meurs; Conny van Holten-Neelen; Marja Smits-Te Nijenhuis; Marion J Kolijn-Couwenberg; P Martin van Hagen; Robert W A M Kuijpers; Herbert Hooijkaas; Willem A Dik Journal: Graefes Arch Clin Exp Ophthalmol Date: 2013-04-20 Impact factor: 3.117
Authors: Shayma Jawad; Baoying Liu; Zhiyu Li; Robert Katamay; Mercedes Campos; Lai Wei; H Nida Sen; Diamond Ling; Fernando Martinez Estrada; Juan Amaral; Chi-Chao Chan; Robert Fariss; Siamon Gordon; Robert B Nussenblatt Journal: Invest Ophthalmol Vis Sci Date: 2013-09-05 Impact factor: 4.799
Authors: Mayur Choudhary; Ebraheim N Ismail; Pei-Li Yao; Faryan Tayyari; Roxana A Radu; Steven Nusinowitz; Michael E Boulton; Rajendra S Apte; Jeffrey W Ruberti; James T Handa; Peter Tontonoz; Goldis Malek Journal: JCI Insight Date: 2020-01-16
Authors: Christopher B Toomey; Una Kelly; Daniel R Saban; Catherine Bowes Rickman Journal: Proc Natl Acad Sci U S A Date: 2015-05-19 Impact factor: 11.205