Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy.
Vision loss associated with ischemic diseases such as retinopathy of prematurity and diabetic retinopathy are often due to retinal neovascularization. While significant progress has been made in the development of compounds useful for the treatment of abnormal vascular permeability and proliferation, such therapies do not address the underlying hypoxia that stimulates the observed vascular growth. Using a model of oxygen-induced retinopathy, we demonstrate that a population of adult BM-derived myeloid progenitor cells migrated to avascular regions of the retina, differentiated into microglia, and facilitated normalization of the vasculature. Myeloid-specific hypoxia-inducible factor 1alpha (HIF-1alpha) expression was required for this function, and we also demonstrate that endogenous microglia participated in retinal vascularization. These findings suggest what we believe to be a novel therapeutic approach for the treatment of ischemic retinopathies that promotes vascular repair rather than destruction.
Ritter
Matthew R
MR
Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Banin
Eyal
E
Moreno
Stacey K
SK
Aguilar
Edith
E
Dorrell
Michael I
MI
Friedlander
Martin
M
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004596:Electroretinography / Q000379:methods; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism / Q000502:physiology; D007150:Immunohistochemistry; D007511:Ischemia / Q000150:complications; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology* / Q000378:metabolism; D023461:Myeloid Progenitor Cells / Q000166:cytology* / Q000502:physiology; D012160:Retina / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012164:Retinal Diseases / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D015861:Retinal Neovascularization / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D014945:Wound Healing / Q000502:physiology
D051795:Hypoxia-Inducible Factor 1, alpha Subunit