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Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy
Matthew R. Ritter, … , Michael I. Dorrell, Martin Friedlander
Matthew R. Ritter, … , Michael I. Dorrell, Martin Friedlander
Published December 1, 2006
Citation Information: J Clin Invest. 2006;116(12):3266-3276. https://doi.org/10.1172/JCI29683.
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Research Article

Myeloid progenitors differentiate into microglia and promote vascular repair in a model of ischemic retinopathy

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Abstract

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 1α (HIF-1α) 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.

Authors

Matthew R. Ritter, Eyal Banin, Stacey K. Moreno, Edith Aguilar, Michael I. Dorrell, Martin Friedlander

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Figure 1

Retinal vascular development in normal and OIR mice.

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Retinal vascular development in normal and OIR mice.
The mouse is born w...
The mouse is born with a largely avascular retina (A and B). During the first postnatal week, superficial retinal vessels grow radially from the optic nerve head (C). The deep retinal vasculature is established through branching of the superficial layer during the second week (D). A third intermediate plexus of vessels forms, and the mature retinal vasculature is established at around P30 (E and F). Exposure to hyperoxia causes central vaso-obliteration (G), and after returning to normoxia at P12, characteristic preretinal neovascular tufts form at the interface between the vascularized (peripheral) and avascular (central) retina (H). (I–N) Lin–HSCs promote vascular repair in the OIR model. Lin–HSC injected intravitreally prior to oxygen exposure dramatically accelerated revascularization compared with the vehicle-treated fellow eye at P17. While retinas treated with vehicle showed partial absence of the superficial vasculature (I) and complete absence of the deep retinal vasculature (K and M), the Lin–HSC-treated eye showed relatively normal retinal vasculature (J, L, and N). (O) A dramatically higher proportion of eyes treated with Lin–HSC were fully revascularized at P17 compared with control eyes. Vessels were visualized by cardiac perfusion of fluorescein-dextran in A–F, I, and J (B, D, and F are images taken from 3D renderings rotated 90 degrees), and by GS lectin in G, H, and K–N. Nuclei in K–N were labeled with DAPI (blue). RE, right eye; LE, left eye. Magnification, ×4 (A, C, E, G, and H), ×10 (I and J), ×60 (B, D, and F).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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