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Bliss O'Bryhim, R. Sid White, Robert Symons; Endothelial Progenitor Cells in Bone Marrow, Blood, and Retina Respond Dynamically to Murine Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):4536.
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Bone marrow-derived endothelial progenitor cells (EPCs) have been shown to contribute to angiogenesis in a variety of pathologies, including metastatic disease, wound healing, and diabetic vascular disorders. Recent work has indicated that EPCs additionally play an important role in both retinopathy of prematurity (ROP) and in the murine model of ROP, oxygen-induced retinopathy (OIR). The purpose of this study is to characterize response of this cell population to OIR during vaso-obliteration and revascularization.
C57BL/6J pups were exposed to 75% oxygen for 120 hours beginning on post-natal day 7 (P7). Mice were sacrificed at daily time points from P7 to P13, and also at P7.5 and P9.5. Live, CD45-/CD34+/CD133+ EPCs were enumerated in bone marrow and blood samples using flow cytometry and expressed as a fraction of all live/CD45- cells. Left retinas were stained for the presence of CD34+/CD133+ EPCs and were counted by an observer blinded to date. Corresponding right retinas were stained with isolectin B4, and the avascular area was measured using ImageJ software.
The number of CD34+/CD133+ cells in the bone marrow decreased initially in response to hyperoxia from P7 to P8, with a peak increase on P9 (0.817%) followed by a gradual decline to 0.270% on P13 (Figure). Circulating CD34+/CD133+ cells increased early in OIR but declined ten-fold from P8 (0.310%) to P10 (0.030%), after which the number increased through P12. The number of CD34+/CD133+ cells recruited to the retina mirrored patterns of circulating cells, with 2 peaks of recruitment on P7.5 (53.7cells/mm2) and P11 (40.3cells/mm2). Retinal avascular areas increased ten-fold from P7 to a maximum on P11 (5.14mm2), and began to decrease by P12.
Bone marrow-derived EPCs are a dynamic population of cells that respond to tissue injury caused by extended hyperoxic stress. Further studies are needed to clarify if the influx of EPCs into the retina on P11 is directly responsible for reduction in avascular area between P11 and P12. A better understanding of their recruitment from the bone marrow to the retina where they contribute to vascular repair may serve to improve therapies available for vasoproliferative retinopathies, including ROP.
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