Chemokine Profile and the Alterations in CCR5-CCL5 Axis in Geographic Atrophy Secondary to Age-Related Macular Degeneration

Abstract

Purpose: Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) is a progressive disease with no treatment option. Previous studies show chemokine-mediated recruitment of immune cells in the retina, and therefore we investigated systemic levels of chemokines and chemokine receptors in patients with GA.

Methods: This observational prospective study was conducted at a single center. We included 122 participants with no immune disease: 41 participants with GA and no choroidal neovascularization, 51 patients with neovascular AMD, and 30 healthy control individuals. Flow cytometric analysis was used to detect expression level of C-C chemokine receptor (CCR)1, CCR2, CCR3, CCR5, and C-X-C motif chemokine receptor (CXCR)3 on peripheral blood mononuclear cells (CD14+ monocytes, CD4+ T cells, CD8+ T cells). Plasma levels of C-C motif ligand (CCL)11, C-X-C motif chemokine (CXCL)10, and CCL5 were measured by specific immunoassays. Enlargement rate of GA lesion was measured from autofluorescence images.

Results: Participants with GA have a specific chemokine profile with a higher expression of CCR5 than healthy controls in peripheral blood mononuclear cells, and a higher plasma levels of CCL-5. Further, GA was associated with higher monocytic expression of CCR2 than in neovascular AMD. We found that a high expression level of CCR5 on CD8+ T cells was associated with slower enlargement rate of atrophic lesion.

Conclusions: The study showed an association between systemic chemokine profile and GA formation. Further studies are needed to fully elucidate the possible role of systemic chemokine regulation in mediating pathogenesis of GA.

Figure.

Enlargement rate of GA during 1 year was square root transformed (SQRT) for baseline area and plotted against plasma levels of CCL5, CCR5+ CD14+ monocytes, CCR2+ CD14+ monocytes, CXCR3+ CD14+ monocytes, CCR5+ CD4+ T cells, and CD8 CCR5+ T cells). This revealed a moderate but significant association between progression rate and CCR5 expression on CD8+ T cells.