Abstract
The C-C chemokine receptor type 3 (CCR3) is the receptor for eotaxins (CCL-11, 24, 26), RANTES (CCL-5) and MCP-3 (CCL-7). It was reported that an inhibition of CCR3 by antagonists or antibodies reduces the degree of laser-induced choroidal neovascularization in mice, a model for wet age-related macular degeneration (AMD). Although several chemokine receptors have the potential of reducing the degree of the chronic inflammation in experimental dry AMD, the association of CCR3 remains unknown. The purpose of this study was to determine the role played by CCR3 in the death of 661W cells which are cells of a murine photoreceptor-derived cell line as an in vitro model of dry AMD. The expression of CCR3 was increased in the 661W cells after light exposure. Inhibition of CCR3 reduced the rate of cell death induced by light exposure. A blockade of CCR3 signaling by CCR3 silencing and two kinds of CCR3 antagonists, SB 328437 and SB 297006, reduced the rate of light-induced cell death. In addition, CCR3 inhibition decreased the level of reactive oxygen species and the activation of caspase-3/7 induced by light exposure. These findings indicated that the CCR3 blockade should be considered for the treatment of the dry AMD.
Highlights
There are two types of age-related macular degeneration (AMD), atrophic and exudative AMD
C-C chemokine receptor type 3 is expressed in normal murine retinas (Wang et al, 2016) and our western blotting results showed that CCR3 was expressed in 661W cells, a mouse photoreceptor-derived cell line
The level of the mRNA of Ccr3 was increased at 6 h after light exposure without the increase of Ccl11 which is the ligand of CCR3 (Figures 1B,C)
Summary
There are two types of age-related macular degeneration (AMD), atrophic (dry) and exudative (wet) AMD. AMD is an important retinal disease because it causes a severe decrease of central vision, and it affects more than 10 million people in the world. The pathological processes in eyes with dry AMD induce retinal pigment epithelium (RPE) atrophy (Liang and Godley, 2003) and enhance the degree of photoreceptor cell death caused by excessive light exposure and oxidative stress (Shahinfar et al, 1991; Beatty et al, 2000). The photoreceptor cell death that is accelerated by oxidative stress leads to a generation of reactive oxygen species (ROS) (Dunaief et al, 2002). The damage of the photoreceptors and RPE cells in the macula is the cause of the reduced vision, and geographic atrophy of the fundus in eyes with dry AMD
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