Amyloid β Enhances Migration of Endothelial Progenitor Cells by Upregulating CX3CR1 in Response to Fractalkine, Which May Be Associated With Development of Choroidal Neovascularization

Objective—Deposits that accumulate beneath retinal pigment epithelium, called drusen, are early signs of age-related macular degeneration (AMD). We have shown that amyloid β (Aβ) is present in drusen, and Aβ may be involved in AMD development. We have also shown that endothelial progenitor cells (EPCs) may contribute to the development of choroidal neovascularization (CNV). Thus, the purpose of this study was to investigate the role played by CX3CR1, a chemokine receptor, in EPC migration and CNV formation.

Methods and Results—EPCs collected from human umbilical cords were found to express higher levels of CX3CR1 than human umbilical vein endothelial cells, and exposure of EPCs to Aβ caused further upregulation of CX3CR1. This upregulation was decreased by blocking fractalkine, a ligand of CX3CR1. Exposure of EPCs to fractalkine increased their migration, but pretreatment with Aβ enhanced the migration. The fractalkine-induced EPC migration was more inhibited by EPCs derived from CX3CR1^−/− mice than wild-type mice. The area of laser-induced CNV was significantly smaller in wild-type mice that received bone marrow transplantation from CX3CR1^−/− mice than in those that received transplantation from wild-type mice.

Conclusion—These data suggest that Aβ enhances EPC migration through the upregulation of CX3CR1. This upregulation might play a role in development of CNV.