Role of CD44⁺Stem Cells in Mural Cell Formation in the Human Choroid: Evidence of Vascular Instability Due to Limited Pericyte Ensheathment

Abstract

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.

Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease

“…Larger choroidal vessels, however, are SMA positive Fig. 4C; (Chan-Ling et al, 2011b). Immunohistochemistry staining for desmin, an accepted pericyte marker, confirmed this negative result in human choroidal pericytes (Fig.…”

“…Further, large numbers of proliferating astrocytes were shown to accompany the developing vessels as they migrate across the primate retina from the optic nerve (Sandercoe et al, 1999; Chan-Ling et al, 2009). For details on the relationship between the astrocytic and vascular cells lineages see Chan-Ling et al (2011b, 2004a) and Dorrell et al, 2002. Although not directly proven, the close correlation in topography and timing between VEGF expression by neuroglia and vessel growth (Stone et al, 1995) supports the contribution of glial cells to vessel formation and survival.…”

“…While less is known about the cellular mechanisms and molecular cues that regulate the growth of blood vessels in the choroid than in the retina, recent studies have added to the understanding of the formation of the human choroidal vasculature (Hasegawa et al, 2007; Chan-Ling et al, 2011b, 2011a). It is evident, that choroidal vessels form earlier than those in the retina.…”

“…Both cell types are in direct communication via gap junctional complexes (Oku et al, 2001) and share a common basement membrane. Regarding pericyte-to-endothelial cell ratios, a recent study of the human retina, utilizing ultrastructural criteria, showed a 94.5% frequency of pericyte coverage on human retinal capillaries (Chan-Ling et al, 2011b). Therefore, the retinal microvasculature is characterized by a uniquely high density of pericytes, substantially greater than that of human choriocapillaris, with an 11% relative frequency of pericyte coverage (Tilton et al, 1985; Chan-Ling et al, 2011b) or cerebral capillaries (Frank et al, 1987).…”

“…Regarding pericyte-to-endothelial cell ratios, a recent study of the human retina, utilizing ultrastructural criteria, showed a 94.5% frequency of pericyte coverage on human retinal capillaries (Chan-Ling et al, 2011b). Therefore, the retinal microvasculature is characterized by a uniquely high density of pericytes, substantially greater than that of human choriocapillaris, with an 11% relative frequency of pericyte coverage (Tilton et al, 1985; Chan-Ling et al, 2011b) or cerebral capillaries (Frank et al, 1987). In addition to numerous morphological characteristics, venules can be distinguished from arterioles by the size of the capillary-free zone around them; the zone is narrower around venules (Hogan and Feeney, 1963).…”