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Tailoi Chan-Ling, Mark E. Koina, Janet R. McColm, Jane E. Dahlstrom, Elaine Bean, Sam Adamson, Steven Yun, Louise Baxter; Role of CD44+ Stem Cells in Mural Cell Formation in the Human Choroid: Evidence of Vascular Instability Due to Limited Pericyte Ensheathment. Invest. Ophthalmol. Vis. Sci. 2011;52(1):399-410. doi: 10.1167/iovs.10-5403.
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To examine mural cell differentiation and pericyte ensheathment during human choroidal vascular formation and into adulthood.
Triple- and double-labeled immunohistochemistry (alpha-smooth muscle actin [αSMA], desmin, NG2, calponin, caldesmon, CD44, CD34, and CD39) were applied to human fetal (8–32 weeks' gestation) and adult choroidal and retinal wholemounts and histologic cross-sections. Transmission electron microscopy (TEM) was also undertaken.
Early in development CD44+ stem cells also stained with αSMA and CD39, suggesting a common precursor. At 12 weeks' gestation, αSMA+ mural precursor cells, confirmed by TEM, were found scattered and isolated over the primordial vascular tree. During development, αSMA+ cells formed a continuous sheath around large arterioles; in veins there were gaps in αSMA expression. The choriocapillaris had an extensive vascular bed but limited coverage by αSMA+ and NG2+ mural cells. Calponin was expressed only on large vessels, and no caldesmon was detected. Pericyte ensheathment of adult capillaries was 11% for choroid versus 94% for retina. Remarkably, choroidal pericytes had no visible intermediate filaments (IFs) on TEM, though IFs were present in retinal pericytes. Neither retinal nor choroidal pericytes stained with desmin.
CD44+ stem cells are involved in the formation of mural cells in the human choroidal vasculature. A marked reduction in pericyte ensheathment of human choroidal vessels suggests a permanently open “plasticity window” and a predisposition to vascular instability and poor autoregulatory ability.
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