Brain and Retinal Pericytes: Origin, Function and Role

Abstract

Pericytes are specialized mural cells located at the abluminal surface of capillary blood vessels, embedded within the basement membrane. In the vascular network these multifunctional cells fulfil diverse functions, which are indispensable for proper homoeostasis. They serve as microvascular stabilizers, are potential regulators of microvascular blood flow and have a central role in angiogenesis, as they for example regulate endothelial cell proliferation. Furthermore, pericytes, as part of the neurovascular unit, are a major component of the blood-retina/brain barrier. CNS pericytes are a heterogenic cell population derived from mesodermal and neuro-ectodermal germ layers acting as modulators of stromal and niche environmental properties. In addition, they display multipotent differentiation potential making them an intriguing target for regenerative therapies. Pericyte-deficiencies can be cause or consequence of many kinds of diseases. In diabetes, for instance, pericyte-loss is a severe pathological process in diabetic retinopathy (DR) with detrimental consequences for eye sight in millions of patients. In this review, we provide an overview of our current understanding of CNS pericyte origin and function, with a special focus on the retina in the healthy and diseased. Finally, we highlight the role of pericytes in de- and regenerative processes.

Keywords: blood flow regulation; blood retina barrier; pericytes; retinal diseases; tissue regeneration.

Figure 1

Localization of pericytes within the retinal vasculature. (A) Retinal vasculature, showing a single neural glial antigen 2 (NG2)-positive (green) vSMCs layer on arterioles (art) and single NG2-positive pericytes on capillaries (c, arrowheads; in accordance with results in Trost et al., 2015). (B) Illustration of the localization of pericytes on capillaries. (B′) Pericytes are located abluminal of endothelial cells, (B″) wrapping around the capillary, embedded within the same basement membrane as demonstrated in a capillary cross-section.

Figure 2

Identification and discrimination of pericytes from vascular smooth muscle cells (vSMCs) in the retina visualizing NG2 and alpha smooth muscle actin (aSMA) protein expression. (A) NG2 immunopositivity can be detected in both, retinal pericytes (representative arrow) and aSMA positive arteriolar SMCs (representative arrowhead). (B) Retinal capillary pericytes lack the aSMA signal (arrows) and (C) can be therefore discriminated from vSMCs as illustrated in the merged picture (in accordance with results in Trost et al., 2013).

Figure 3

Schematic overview of (the main) pericyte functions.