title: Amyloid beta enhances migration of endothelial progenitor cells by upregulating CX3CR1 in response to fractalkine, which may be associated with development of choroidal neovascularization.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  These data suggest that Aβ enhances EPC migration through the upregulation of CX3CR1. This upregulation might play a role in development of CNV.
authors.affiliation: Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113, Japan.
authors.forename: Jiying
authors.initials: J
authors.lastname: Wang
authors.forename: Kyoko
authors.initials: K
authors.lastname: Ohno-Matsui
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nakahama
authors.forename: Aikou
authors.initials: A
authors.lastname: Okamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Noriaki
authors.initials: N
authors.lastname: Shimada
authors.forename: Manabu
authors.initials: M
authors.lastname: Mochizuki
authors.forename: Ikuo
authors.initials: I
authors.lastname: Morita
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016026:Bone Marrow Transplantation; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D020256:Choroidal Neovascularization / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D054023:Lasers, Semiconductor; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016229:Amyloid beta-Peptides; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; C471885:Cx3cr1 protein, mouse; D053583:Interleukin-1beta; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha