ReviewPericytes and ocular diseases
Introduction
Pericytes are vascular mural cells of mesenchymal origin, embedded in the basement membrane of microvessels (Sims, 1986). For years considered to be the microvessel analogues of vascular smooth muscle cells and to possibly serve the purpose of capillary tone maintenance (Herman and D'Amore, 1985, Joyce et al., 1985a, Joyce et al., 1985b), pericytes have lately been receiving considerable attention as active players in angiogenesis (Hall, 2006, Jain, 2003, von Tell et al., 2006). Genetic studies involving mouse mutants with reduced pericyte coverage of blood vessels showed that these cells have multiple effects on the vasculature: they participate in its development, maturation and remodeling, as well as contribute to normal architecture and regulate permeability (Enge et al., 2002, Hellstrom et al., 2001, Leveen et al., 1994, Lindahl et al., 1997, Soriano, 1994). It is therefore not surprising that pericytes play a role in angiogenic diseases, including those of the eye, and are being considered as targets for treatment.
Section snippets
Pericytes and ocular diseases
Pericytes have been strongly and unequivocally tied to one ocular disease – diabetic retinopathy (DR). Growing evidence implicates these cells in retinopathy of prematurity (ROP), another retinal angiogenic pathology. Consequently, a question whether pericytes are involved in pathological angiogenesis in other parts of the eye, such as the cornea and the choroid, has been raised.
Pericytes as targets for treatment of ocular diseases
In spite of the immense progress in treatment of ocular angiogenic diseases, they still cause a large number of new cases of blindness every year (Antonetti et al., 2006, Drack, 2006). The newest therapies, albeit more efficient at stopping the symptoms, are not always able to restore the vision of patients, and are not without side effects (Bradley et al., 2007). Given the participation of pericytes in angiogenic eye diseases, they appear to be attractive targets for new methods of treatment.
Concluding remarks
Evidence implicating pericytes in the pathology of eye diseases is mounting. The data described above suggests a working hypothesis to explain how pericytes contribute to ocular pathologies: their loss destabilizes vasculature, increasing its responsiveness to angiomodulators in their microenvironment. In the cases of neovascular eye diseases, the balance of angiomodulators shifts to one favoring angiogenesis, and vessels begin to sprout. Loss of pericytes also appears to compromise the
Acknowledgment
We would like to thank Mr. Peter Mallen (Schepens Eye Research Institute) for his help creating Fig. 1. This work was supported by NIH grant EY016385.
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2017, Toxicology and Applied PharmacologyCitation Excerpt :Pericytes, as part of the neurovascular unit, are a major component of the blood-brain barrier/BRB, assigned for vessel stabilization and neurovascular coupling (Trost et al., 2016). The loss of pericytes, which results in BRB disruption as well as reduced perfusion, is a characteristic pathologic feature of early-stage DR (Motiejunaite and Kazlauskas, 2008; Praidou et al., 2010; Fu et al., 2012). The accumulation of cytotoxic AGE in pericytes and decreases in PDGF levels have been suggested as possible causes of pericyte dropout in DR (Motiejunaite and Kazlauskas, 2008).