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Valentina Marchetti, Matthew Wang, Edith Aguilar, Mauricio Rosenfeld, Glen Nemerow, Martin Friedlander; Human Myeloid Progenitor Cells Target And Accelerate The Regression Of Hyaloid Vasculature In Normal And Pathological Eyes. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4855.
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During the initial development of the eye, oxygenation and consequent development of the retina is provided by the choroidal and hyaloidal vasculature. We previously demonstrated that human cord blood (hCB)-derived myeloid cells target retinal vasculature and provide trophic rescue in a model of Oxygen Induced Retinopathy (OIR). We wanted to examine the targeting of these cells to hyaloidal vessels under normal and pathological growth conditions and their role during hyaloidal vessel growth and/or regression.
HCB CD14+ cells, infected with Adenovirus 5-GFP, were injected intravitreally in postnatal day seven (P7) mice. Human eGFP+ cells and murine vessels were visualized in vivo using the Heidelberg Spectralis and characterized ex vivo by confocal microscopy at different time points after injection. Branch points and total pixel counts were quantified for each animal. Z-stacks acquired by confocal microscopy were constructed and visualized by Volocity software.
EGFP+ cells target the hyaloidal vessels exhibiting morphological differentiation around and along the vasculature. Human eGFP+ cells were found incorporating within the vessel lumen. Thin elongated endothelial-like cells were observed within narrow and small vessels; ramified human cells were seen wrapping around large dilated vessels. EGFP+ cells reduced hyaloidal branch points by 60% and the total vessel area by 35% compared to untreated eyes. Targeting, morphology and accelerated hyaloidal vascular regression after treatment with CD14+ cells was similar under conditions of OIR.
We have identified a human CB-derived CD14+ population that targets hyaloidal vasculature and promotes accelerated regression in normal eyes. Human cells also accelerated hyaloidal vascular regression in the OIR model and, thus, modify the level of oxygen perfusion through the vessels at an early stage in the retinal development. Transcriptomic analysis of injected human cells and target murine tissue reveals differential gene expression associated with the CD14+ cells activities. The use of Adenoviral vectors encoding various trophic factors could modulate the role of CB derived CD14+, providing more efficient and safer methods of ocular gene delivery.
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