Abstract
Purpose: :
Experimental data from Age- related Macular Degeneration (AMD) patients and rodent models of the disease have implicated both chemokines receptors signaling and macrophages in the pathogenesis of AMD. However, their specific roles in the disease are not well understood. We aim to test the association among expression of chemokines receptors in sub-populations of white blood cells and AMD.
Methods: :
Peripheral blood was drawn from treatment-naïve neovascular AMD (NV-AMD) patients (n=17; 9 females, 8 males) and age- matched control subjects (n=15; 8 females, 7 males). Immunophenotyping was performed on whole blood using antibodies recognizing various white blood cell types (T, B, and NK lymphocytes, CD14+CD16- and CD14+CD16+ monocytes). Expression of CCR1, CCR2, CCR5, CX3CR1, and CXCR4 chemokines receptors was assayed on each cell type by flow cytometry.
Results: :
The number of cells belonging to each of the white blood cell sub-populations tested was similar in NV-AMD patients and controls. Average (±SEM) percentage of cells expressing CCR2 was increased in the sub-population of CD14+CD16+ monocytes from AMD patients (15.9±3.6) compared with controls (6.1±1.6; P=0.02; T-test). A trend towards increased CCR1 expression on CD14+CD16+ monocytes from AMD patients (7.4±2.5) vs. controls (2.5±0.8; P= 0.09; T-test) was also observed. CCR2 and CCR1 expression on T cells, B cells, NK cells, and CD14+CD16- subpopulation of monocytes were similar between patients and controls. Similarly, expression of CCR5, CX3CR1, and CXCR4 was similar in patients and controls on every cell type tested.
Conclusions: :
Expression of the CCR2 chemokine receptor is up-regulated by the CD14+CD16+ subset of monocytes in NV-AMD patients. This data implicates CCR2 in the pathogenesis of NV-AMD. Additional investigation is required to elucidate whether increased CCR2 expression on monocytes underlie macrophage accumulation in retinas of AMD patients.
Keywords: age-related macular degeneration • gene/expression • inflammation