Pericytes

Role of Pericytes in Maintaining Vascular Integrity

Pericytes are the vascular supporting cell type most intimately associated with the retinal vascular endothelium. They are elongated, polymorphic cells of mesenchymal origin that are sandwiched between the vascular endothelial cells and the perivascular astrocytes and are separated from each by a basement membrane, except where pericytes and endothelial cells make direct contact (Figure 1). Pericytes surround the vascular endothelium and help regulate endothelial cell growth, vessel stability, and vascular permeability. Pericyte loss, which occurs in diabetic retinopathy, is accompanied by neovascularization and vascular leakage. Pericytes contain extensive networks of intermediate filaments, which, depending on the species and tissue, consist of vimentin with or without desmin. Pericytes also contain contractile proteins, such as smooth muscle-specific isoforms of actin (a-SMA) and myosin, cyclic GMP-protein kinase, and tropomyosin, which may help in regulating blood flow [1, 2]. a-SMA, which is also found in vascular smooth muscle cells, is the most commonly used marker for the recognition and immunolocalization of pericytes [3, 4], but an RNA probe directed against PDGFb-receptors can also be used to visualize pericytes [5].

Pericyte Development in the Retinal Vasculature

During vascularization of the rat retina, pericytes are recruited after the formation of the primary endothelial cell plexus. Pericytes migrate into the eye from arterioles branching from the hyaloid artery in the optic nerve. As the plexus matures, pericytes migrate from the arterioles toward the venules. In rats and mice, the recruitment of pericytes lags behind the formation of the endothelial plexus by several days to a week [3, 5], although some pericytes have been found in small vessels of the mouse as early as postnatal day 1 (P1)[6]. They are specifically associated with areas of the vascular network that contain collagen IV [5]. By P10, pericytes cover the primary vessel branches of the superficial retinal vascular bed in rats and by P18, they have

Figure 1 Ultrastructure of a normal inner retinal vessel. The tubular configuration of the vascular endothelial cells (E) forms a lumen, which contains a red blood cell. The endothelial cells are connected by tight junctions (zonula occludens) (arrows), which help establish the blood-retinal barrier. Pericytes (P) envelop the vascular endothelium and astrocytes (A) cover the pericytes. A basal lamina separates the astrocytes from the pericytes and the pericytes from the endothelial cells, except where there is direct cell-to-cell contact. The arrowhead shows a point of direct contact between a pericyte and a vascular endothelial cell. (see color insert)

Figure 1 Ultrastructure of a normal inner retinal vessel. The tubular configuration of the vascular endothelial cells (E) forms a lumen, which contains a red blood cell. The endothelial cells are connected by tight junctions (zonula occludens) (arrows), which help establish the blood-retinal barrier. Pericytes (P) envelop the vascular endothelium and astrocytes (A) cover the pericytes. A basal lamina separates the astrocytes from the pericytes and the pericytes from the endothelial cells, except where there is direct cell-to-cell contact. The arrowhead shows a point of direct contact between a pericyte and a vascular endothelial cell. (see color insert)

reached the secondary and tertiary branches. Even though the deep capillary bed is completely formed by P10, pericytes do not cover these vessels until more than three weeks after birth, when no further vascular remodeling occurs [3]. It appears that pericytes are more involved in the maturation and remodeling of retinal vessels than in their formation. After the vasculature has formed, many of the vessels regress in more hyperoxic areas. Covering of the vascular endothelium by pericytes arrests endothelial cell proliferation and appears to stabilize the enveloped capillaries, protecting them from regressing. In mice, pericytes are always found on capillaries adjacent to the regressing segment, but never on the regressing arm [6].

The Role of PDGF-B in Pericyte Recruitment and Development

Platelet-derived growth factor-B (PDGF-B) is necessary for pericyte development, because PDGF-B-deficient mice lack pericytes [7]. Not only is PDGF-B essential for pericyte survival, but it is also critical for their migration along capillary endothelial sprouts and for normal pericyte-endothe-lial interactions. Pericytes are the predominant cell type in the developing retina that expresses PDGF-b receptors, which specifically bind PDGF-B. In studies where PDGF-B has been elevated during the time of vascular remodeling, either by endogenous administration [3] or because of overexpression in transgenic mice [4], the increased PDGF-B leads to a disruption of normal pericyte-endothelial cell interactions and disrupted retinal vascular development. Following intravitreal injection of PDGF-B to mice during the time of vessel remodeling, pericytes, which normally are tightly wrapped around vessels, are disorganized and often connected to more than one vessel. This leads to excessive hemorrhage followed by capillary obliteration and the widening of capillary-free zones and the formation of irregularly spaced vascular loops and capillary tangles. The retinal vasculature of these PDGF-B-treated mice is also more vulnerable to oxygen-induced damage. When PDGF-B is administered during the remodeling phase of the deep capillary plexus, but after the remodeling of the superficial plexus is complete (P18), only the deep vessels are affected [3]. Overexpression of PDGF-B in transgenic mice leads to hyperproliferation of pericytes, astrocytes, and endothelial cells. It also results in the disassociation of pericytes and vascular smooth muscle cells from vascular endothelial cells and an impairment of the formation of the deep capillary bed. These effects result in the formation of an underdeveloped vasculature in the retina. The aSMA-positive pericytes in the retinas of these mice are generally found in clusters and are usually round or oblong with a high nucleus-to-cytoplasm ratio and abundant mitochondria and rough endoplasmic reticulum [4].

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

Get My Free Ebook


Post a comment