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T. Chan-Ling, M. Koina, J. R. McColm, J. Dahlstrom, E. Bean, L. Baxter; Limited Pericyte Ensheathment Predisposes Human Choroidal Vessels to Vascular Instability & Poor Blood Flow Regulation. Invest. Ophthalmol. Vis. Sci. 2010;51(13):44.
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During development, smooth muscle cells (SMCs) and pericytes are thought to play an important role in regulating endothelial proliferation, vascular remodelling, vessel stabilisation and synthesis of the extracellular matrix. We sought to examine normal mural cell differentiation and its relationship to vascular formation and related our findings to the different ability of the retina and choroid to autoregulate.
Mural cells were investigated following triple-label immunohistochemistry applied to human retinal and choroidal wholemounts and histological cross sections, aged 8 to 40 weeks gestation (WG). Antibodies to αSMA, Desmin, NG2, Calponin, Caldesmon, CD34 and CD39 were used to visualise the relationship between smooth muscle cells, pericytes and the forming vasculature. Transmission Electron Microscopy (TEM) was also undertaken.
SMA+ mural precursor cells were found scattered and isolated over the primordial vascular tree at 12WG. αSMA+ smooth muscle cells were restricted to major arteries and veins. At 16WG, SMA aggregated into concentric filaments, forming a continuous sheath around large choroidal arteries, whilst in the veins there were gaps in SMA expression. At 18WG the choriocapillaris had an extensive CD34+ vascular bed, but only a small portion of these vessels were ensheathed by SMA+ and NG2+ mural cells. Calponin and Caldesmon (calcium regulating proteins) were expressed only on large arteries, not the veins. Pericyte ensheathment of human adult capillaries as sampled with TEM was 11% in the choroid versus 94.5% in the retina. Desmin is seen on ultrastructural examination as an intermediate filament. In adult choroidal pericytes no intermediate filaments were observed. Remarkably, pericytes, as indicated by Desmin and NG2 labeling and visualisation of intermediate filaments with TEM, were absent on human choroidal capillaries.
We provide evidence in support of the role of CD44+ stem cells in the formation of mural cells of the human choroidal vasculature. Vast amounts of non-vascular associated SMA filaments were observed throughout the stroma, suggestive of a possible role in rapid changes in choroidal volume in emmetroprisation. Moreover, we have provided evidence of a marked difference in pericyte ensheathment between choroidal and retinal vessels, underlying the marked difference in vessel stability and autoregulatory ability reported between the two vascular plexii.
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