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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 2

BM subpopulations accelerate retinal revascularization and reduce preretinal neovascular tuft formation in OIR.

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BM subpopulations accelerate retinal revascularization and reduce preret...
(A–D) Computer-assisted image analysis was used to calculate the area of retinal vessel obliteration (yellow) and preretinal neovascular tuft formation (red) in whole mounts from OIR eyes at P17 (17). (E) Retinas treated with Lin–HSC prior to hyperoxia showed an almost 6-fold reduction in obliterated area versus uninjected controls and an approximately 5-fold reduction compared with vehicle-treated controls. (F) Lin–HSC treatment significantly reduced neovascular tufts compared with uninjected and vehicle-treated eyes. (G) Lin–HSCs reduced obliteration when administered prior to hyperoxia and during hyperoxia (P9 or P11) or just after return to normoxia (P12). inj, injected. (H) Mouse BM contained CD44hi and CD44lo fractions and the Lin–HSC population was enriched for CD44hi cells (red). Insets: Light-scattering properties of the CD44hi cells were typical of monocytes and granulocytes, while those of CD44lo cells were typical of lymphocytes. (I and J) Representative P17 retinas from eyes treated with CD44lo and CD44hi BM cells at P7. (K and L) Areas of obliteration (yellow) and neovascularization (red) at P17. When treated at P7, vascular obliteration (M) and neovascularization (N) were reduced in eyes treated with CD44hi cells with efficacy similar to eyes treated with Lin–HSC cells. Obliteration was similar between eyes treated with Lin–HSC and CD44hi cells, and neovascularization did not differ significantly between these groups (P = 0.25). Values represent mean ± SEM. *P < 10–5; **P ≤ 0.006. Magnification, ×4.

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

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