title: Activation of bone marrow-derived microglia promotes photoreceptor survival in inherited retinal degeneration.
abstract: The role of microglia in neurodegeneration is controversial, although microglial activation in the retina has been shown to provide an early response against infection, injury, ischemia, and degeneration. Here we show that endogenous bone marrow (BM)-derived microglia play a protective role in vascular and neural degeneration in the retinitis pigmentosa model of inherited retinal degeneration. BM-derived cells were recruited to the degenerating retina where they differentiated into microglia and subsequently localized to the degenerating vessels and neurons. Inhibition of stromal-derived factor-1 in the retina reduced the number of BM-derived microglia and accelerated the rate of neurovascular degeneration. Systemic depletion of myeloid progenitors also accelerated the degenerative process. Conversely, activation of BM-derived myeloid progenitors by systemic administration of both granulocyte colony-stimulating factor and erythropoietin resulted in the deceleration of retinal degeneration and the promotion of cone cell survival. These data indicate that BM-derived microglia may play a protective role in retinitis pigmentosa. Functional activation of BM-derived myeloid progenitors by cytokine therapy may provide a novel strategy for the treatment of inherited retinal degeneration and other neurodegenerative diseases, regardless of the underlying genetic defect.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8386, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Sasahara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Otani
authors.forename: Akio
authors.initials: A
authors.lastname: Oishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kojima
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yodoi
authors.forename: Takanori
authors.initials: T
authors.lastname: Kameda
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakamura
authors.forename: Nagahisa
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002470:Cell Survival; D054377:Chemokine CXCL12 / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000502:physiology*; D023461:Myeloid Progenitor Cells / Q000473:pathology / Q000502:physiology; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology*; D012160:Retina / Q000473:pathology*; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000378:metabolism / Q000473:pathology
chemical_list: D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse