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

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 5

Intravitreally injected CD44hi cells take on characteristics of retinal microglia.

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Intravitreally injected CD44hi cells take on characteristics of retinal ...
(A) Transplanted CD44hi cells (green) injected at P7 localized to and survived within the avascular central retina at P12. Many cells labeled with GS lectin (red), which labels microglia in the retina, and thus appear yellow. (B) CD44hi cells (green, arrowhead) often assumed a ramified morphology similar to endogenous microglia. Endogenous microglia (arrow) and retinal vessels were stained with GS lectin (red). (C–F) In addition to the intervascular localization shown in B, transplanted CD44hi cells also assumed a perivascular localization and were positive for F4/80 (C) and CD11b (E), markers of macrophages/microglia. D and F are merges with GFP expression (green), GS lectin (blue), and F4/80 (red, D) or CD11b (red, F). (G) CD44hi cells assumed both perivascular and intervascular localization (3D image). Note the ramified, microglia-like morphology of the GFP+ cells. (H and I) CD44hi cells did not form any portion of the vessel lumen, as shown by 3D imaging. The image in H was rotated such that the vessel could be viewed in cross-section. (I) Numbered positions indicated in H show that the GFP+ cell (green) was found on the outside of the CD31-labeled (dotted) endothelial lumen. (J and K) A single transplanted CD44hi cell (3D image) shown en face (J) and in profile (K) demonstrating the highly ramified morphology taken on by these cells after injection into the eye. Magnification, ×10 (A), ×60 (B–I), ×120 (J and K).