title: Bone marrow-derived monocyte lineage cells recruited by MIP-1β promote physiological revascularization in mouse model of oxygen-induced retinopathy.
abstract: Recent clinical observations have indicated that vascular endothelial growth factor (VEGF) is a key factor that stimulates the development of preretinal pathological neovascularization (NV). However, it has not been established how intraretinal physiological revascularization of hypoxic avascular areas is regulated. Our earlier study on the gene expression profile of hypoxic retinas in a mouse model of oxygen-induced retinopathy (OIR) showed that macrophage inflammatory protein-1β (MIP-1β) was the most upregulated protein. The purpose of this study was to investigate the role played by MIP-1β in recruiting bone marrow-derived monocyte lineage cells (BM-MLCs) in a mouse model of OIR. Our results showed that MIP-1β was upregulated, and its receptor, CCR5, was expressed in BM-MLCs in the hypoxic inner retina. Neutralizing Ab against MIP-1β reduced the infiltration of BM-MLCs into the OIR retinas and increased the avascular area and preretinal neovascular tufts. A very strong significant correlation was found between the area of the preretinal neovascular tufts and the avascular area, regardless of the extent of BM-MLC infiltration into the OIR retinas. Additional treatment with VEGF-A-neutralizing Ab showed that the MIP-1β-regulated pathological NV strongly depended on VEGF-A, which was probably secreted by the hypoxic avascular retinas. These results indicate that MIP-1β is involved in the recruitment of BM-MLCs, which have a significant role in the physiological revascularization of hypoxic avascular retinas. Overall, these findings indicate that the MIP-1β induction of BM-MLCs might possibly be used to promote intraretinal revascularization and thus prevent the abnormal NV in ischemic vision-threatening retinal diseases.
authors.affiliation: Department of Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Keijiro
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Shigeo
authors.initials: S
authors.lastname: Yoshida
authors.forename: Shintaro
authors.initials: S
authors.lastname: Nakao
authors.forename: Yukio
authors.initials: Y
authors.lastname: Sassa
authors.forename: Ryo
authors.initials: R
authors.lastname: Asato
authors.forename: Riichiro
authors.initials: R
authors.lastname: Kohno
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Arima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kita
authors.forename: Ayako
authors.initials: A
authors.lastname: Yoshida
authors.forename: Kenoki
authors.initials: K
authors.lastname: Ohuchida
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Ishibashi
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D019070:Cell Lineage; D002465:Cell Movement; D054407:Chemokine CCL4 / Q000032:analysis / Q000502:physiology*; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000502:physiology*; D010100:Oxygen / Q000633:toxicity*; D019713:Receptors, CCR5 / Q000032:analysis; D012160:Retina / Q000737:chemistry / Q000378:metabolism; D012164:Retinal Diseases / Q000503:physiopathology*; D015861:Retinal Neovascularization / Q000209:etiology*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: C496535:Ccl4 protein, mouse; D054407:Chemokine CCL4; D019713:Receptors, CCR5; D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen