Pericytes in Vascular Biology A Brief Overview

Retinal capillaries consist of three elementary structures: endothelial cells, basement membrane tubes, and intramural pericytes that are located within the basement membrane (Figure 1). Pericytes both in humans and in rodents are present in the retina at an almost 1: 1 ratio with endothelial cells. Their high numbers in the retina, even higher than the numbers in the brain, has been associated with the tightness of the blood-retinal barrier.

The recruitment of pericytes to the vessel wall has been most extensively studied in rodents. Pericytes arrive in the retinal vessel closely following the sprouting tip of the growing capillary. With improved techniques circumventing the problem that certain markers (such as SMA) are not expressed in pericyte subpopulation invading the CNS, it emerges that the existing window of plasticity of the developing retinal capillary network is not explained by pericytes lagging behind the sprouting of endothelial cells. The resistance of retinal capillaries to regressive signals such as hyperoxia marks the end of the vascular plasticity. From in vivo studies in newborn mice, it is likely a variety of growth factors such as vascular endothelial growth factor (VEGF), the angiopoietins, and others associated with pericyte recruitment such as platelet-derived growth factor (PDGF)-B and TGF-b are involved in the maturation of retinal capillaries. However, the precise mechanisms are not yet defined, and the role of pericytes is still undetermined except for the fact that their attachment to the vessel wall does not coincide with the resistance of the capillaries to regression. With regard to the pathogenesis of diabetic retinopathy, which develops almost exclusively in the mature retina, pericytes are crucially involved in promoting

Figure 1 Retinal digest preparation of a human retina, obtained postmortem, of a patient with type 1 diabetes. A microaneurysm is positioned next to acellular capillaries. Original magnification 600x. Periodic acid-Schiff (PAS) staining.

the survival of retinal capillaries. Active disruption of the cellular cross-talk between ECs and pericytes leads to aberrant remodeling. While pericyte recruitment to capillaries in the developing retina is initially PDGF-Rb dependent, capillaries from older mice become resistant to PDGF-B depletion. From these data, it emerges that pericytes in the developing retina control sprouting and vessel remodeling, whereas in the adult/matured retina, they serve as survival-supporting cells for endothelial cells. This is also reflected by experiments showing that the adult retina is resistant to hyperoxia-induced vascular regression, even when pericyte numbers are reduced, suggesting that mechanisms independent of the physical presence of pericytes determines plasticity.

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