Abstract
Retinal microvasculature is crucial for the visual function of the neural retina. Pericytes and endothelial cells (ECs) are the two main cellular constituents in the retinal microvessels. Formation, maturation, and stabilization of the micro-vasculatures require pericyte-endothelial interactions, which are perturbed in many retinal vascular disorders, such as retinopathy of prematurity, retinal vein occlusion, and diabetic retinopathy. Understanding the cellular and molecular mechanisms of pericyte-endothelial interaction and perturbation can facilitate the design of therapeutic intervention for the prevention and treatment of retinal vascular disorders. Pericyte-endothelial interactions are indispensable for the integrity and functionality of retinal neurovascular unit (NVU), including vascular cells, retinal neurons, and glial cells. The essential autocrine and paracrine signaling pathways, such as Vascular endothelial growth factor (VEGF), Platelet-derived growth factor subunit B (PDGFB), Notch, Angipointein, Norrin, and Transforming growth factor-beta (TGF-β), have been well characterized for the regulation of pericyte-endothelial interactions in the neo-vessel formation processes (vasculogenesis and angiogenesis) during embryonic development. They also play a vital role in stabilizing and remodeling mature vasculature under pathological conditions. Awry signals, aberrant metabolisms, and pathological conditions, such as oxidative stress and inflammation, can disrupt the communication between pericytes and endothelial cells, thereby resulting in the breakdown of the blood-retinal barrier (BRB) and other microangiopathies. The emerging evidence supports extracellular exosomes’ roles in the (mis)communications between the two cell types. This review summarizes the essential knowledge and updates about new advancements in pericyte-EC interaction and communication, emphasizing the retinal microvasculature.
Highlights
Retinal microvasculature supports the neural retina’s visual function by supplying the retinal cells with nutrients and oxygen and draining the waste out of the tissues
The superfamily of TGF-β contains more than 30 members, including TGF-β1, activin, nodals, and bone morphogenetic proteins (BMP 1-20), and they can bind with several classes of receptors: activin-like kinases (ALKs), TGF-β receptors (TGFBRs), and BMP receptors (BMPRs) [31]
Our study further revealed that PlGF negatively regulates human retinal ECs (HRECs) barrier function by suppressing the pentose phosphate pathway (PPP) and glucose-6-phosphate dehydrogenase (G6PD) activity, which generates NADPH and reinforces antioxidant defense [60]
Summary
Retinal microvasculature supports the neural retina’s visual function by supplying the retinal cells with nutrients and oxygen and draining the waste out of the tissues This is critically important because the retina is a metabolically active neural tissue, consuming high levels of oxygen. Retinal microvasculature possesses the specialized features necessary for the maintenance of environmental homeostasis in the retina One such feature is the blood-retinal barrier (BRB), an analog of the blood-brain barrier (BBB) in the brain, which prevents the free access of blood, especially large molecular weight blood substances, to the delicate neural tissue. Various disease and stress conditions, such as ischemia, inflammation, and diabetic retinopathy (DR), can cause the breakdown of BRB, perturb the communication of NVU cells, and disrupt the architecture of retinal microvasculature, thereby exacerbating inflammation, ischemic damage, and pathological process [2,3,4]. Pericyte-endothelial interactions in pathological conditions are disturbed by various factors, such as altered oxygen levels, reactive oxygen species, advanced glycation end products, increased leukocytes adhesion, inflammatory cytokines, and chemokines
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