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Jiying Wang, Kyoko Ohno-Matsui, Takeshi Yoshida, Noriaki Shimada, Manabu Mochizuki, Ikuo Morita; Amyloid β Enhances Migration Of Endothelial Progenitor Cells Via Upregulation Of CX3CR1. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3194.
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© ARVO (1962-2015); The Authors (2016-present)
Amyloid β (Aβ) is accumulated within drusen and reportedly critical for pathogenesis of age-related macular degeneration (AMD). Endothelial progenitor cells (EPC) contributed to the development of CNV via matrix degrading enzyme; cathepsin L. We previously reported that Aβ enhanced the production of pro-inflammatory cytokines in EPC (ARVO2010). In the present study we investigated the molecular mechanism of the recruitment of EPC to subretinal space secondary to Aβ accumulation.
EPC were isolated from the cultivation of mononuclear cells in human cord blood from healthy newborns. EPC were stimulated by Aβ or pro-inflammatory cytokines (IL-1β, TNF-α) . The mRNA expression and protein production of fractalkine and its receptor; CX3CR1 was analyzed by real-time PCR and western blot. Migratory activity was measured by Boyden chamber assay. The role of CX3CR1 in choroidal neovascularization (CNV) development was analyzed using laser-induced CNV model.
IL-1β, TNF-α significantly increased the expression and protein production of fractalkine. Aβ treatment induced a significant increase of CX3CR1 expression and protein production. In Boyden chamber assay, fractalkine caused a remarkable migration of EPC in a dose-dependent manner. Fractalkine-induced migration of EPC was significantly enhanced in Aβ-treated EPC compared to non-treated EPC. Laser-induced CNV was significantly suppressed in CX3CR1-/- mice compared to wild type mice.
These results suggest the possibility that Aβ causes the migration of EPC to the area of drusen via up-regulation of CX3CR1 as well as cytokine-induced up-regulation of fractalkine. This phenomenon might be an important process for the CNV development in AMD.
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