Plastic roles of pericytes in the blood–retinal barrier

Park, Do Young; Lee, Junyeop; Kim, Jae Hui; Kim, Kangsan; Hong, Seonpyo; Han, Sungwon; Kubota, Yoshiaki; Augustin, Hellmut G.; Ding, Lei; Kim, Jin Woo; Kim, Hail; He, Yulong; Adams, Ralf H.; Koh, Gou Young

doi:10.1038/ncomms15296

Cited by 244 publications

(229 citation statements)

References 73 publications

Supporting

Mentioning

214

Contrasting

Unclassified

Order By: Relevance

“…Finally, the expression of Tie2 by pericytes has been fiercely debated in the past decades, with extensive characterization of Tie2 expression in cultured pericytes, but a lack of Tie2 expression noted in pericytes in vivo . However, recent evidence has shown that a pericytes‐specific knockout of Tie2 leads to dramatically altered vascular structure, paired with a demonstration of Tie2 acting as a potent pericyte chemokine in vitro, together suggesting that Tie2 signaling may serve an important role in pericyte function.…”

Section: Markers and Models To Study Microvascular Network Architecturementioning

confidence: 99%

Methods to label, image, and analyze the complex structural architectures of microvascular networks

et al. 2019

View full text Add to dashboard Cite

Microvascular networks play key roles in oxygen transport and nutrient delivery to meet the varied and dynamic metabolic needs of different tissues throughout the body, and their spatial architectures of interconnected blood vessel segments are highly complex. Moreover, functional adaptations of the microcirculation enabled by structural adaptations in microvascular network architecture are required for development, wound healing, and often invoked in disease conditions, including the top eight causes of death in the Unites States. Effective characterization of microvascular network architectures is not only limited by the available techniques to visualize microvessels but also reliant on the available quantitative metrics that accurately delineate between spatial patterns in altered networks. In this review, we survey models used for studying the microvasculature, methods to label and image microvessels, and the metrics and software packages used to quantify microvascular networks. These programs have provided researchers with invaluable tools, yet we estimate that they have collectively attained low adoption rates, possibly due to limitations with basic validation, segmentation performance, and nonstandard sets of quantification metrics. To address these existing constraints, we discuss opportunities to improve effectiveness, rigor, and reproducibility of microvascular network quantification to better serve the current and future needs of microvascular research.

show abstract

Section: Markers and Models To Study Microvascular Network Architecturementioning

confidence: 99%

Methods to label, image, and analyze the complex structural architectures of microvascular networks

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Nonetheless, topographic differences of perivascular mural cells in the normal and diseased retina have not yet been evaluated. Meanwhile, pericyte loss as pathogenesis of DR has been extensively studied, including our group [12][13][14][15][16][17], and the arteriolar VSMC alteration of DR has been established [18]. However, the αSMA positive mural cell changes in the diabetic retinal capillaries have also not been well elucidated yet.…”

Section: Introductionmentioning

confidence: 99%

Alpha-Smooth Muscle Actin-Positive Perivascular Cells in Diabetic Retina and Choroid

Kim

Choi

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Structural alterations of pericytes in microvessels are important features of diabetic retinopathy. Although capillary pericytes had been known not to have α-smooth muscle actin (αSMA), a recent study revealed that a specific fixation method enabled the visualization of αSMA along retinal capillaries. In this study, we applied snap-fixation in wild type and streptozotocin-induced diabetic mice to evaluate the differences in vascular smooth muscle cells of the retina and the choroid. Mice eyeballs were fixed in ice-cold methanol to prevent the depolymerization of filamentous actin. Snap-fixated retina showed αSMA expression in higher-order branches along the capillaries as well as the arterioles and venules, which were not detected by paraformaldehyde fixation. In contrast, most choriocapillaris, except those close to the arterioles, were not covered with αSMA-positive perivascular mural cells. Large choroidal vessels were covered with more αSMA-positive cells in the snap-fixated eyes. Diabetes induced less coverage of αSMA-positive perivascular mural cells overall, but they reached higher-order branches of the retinal capillaries, which was prominent in the aged mice. More αSMA-positive pericytes were observed in the choroid of diabetic mice, but the αSMA-positive expression reduced with aging. This study suggests the potential role of smooth muscle cells in the pathogenesis of age-related diabetic retinopathy and choroidopathy.

show abstract

“…Whether an acute drop-out of pericytes in the adult organism leads to altered BBB permeability and alters the permissiveness of vasculature to leukocyte trafficking needs further studies. Pericyte ablation in adult mice using the Pdgfrb -Cre-Er T2 ; DTA mice was reported not to cause immediate BBB permeability changes in the retina and brain 24 ; however, pericyte loss in the brain was not assessed. Our unpublished data show that using the Pdgfrb -Cre-Er T2 ; DTA approach is not effective to deplete adult brain pericytes.…”

Section: Discussionmentioning

confidence: 99%

Pericytes regulate vascular immune homeostasis in the CNS

Torok

Schreiner

Tsai

et al. 2019

Preprint

View full text Add to dashboard Cite

21Brain endothelium possesses several organ-specific features collectively known as the blood-22 brain barrier (BBB). In addition, trafficking of immune cells in the healthy central nervous 23 system (CNS) is tightly regulated by CNS vasculature. In CNS autoimmune diseases such as 24 multiple sclerosis (MS), these homeostatic mechanisms are overcome by autoreactive 25 2 lymphocyte entry into the CNS causing inflammatory demyelinating immunopathology. 26Previous studies have shown that pericytes regulate the development of organ-specific 27 characteristics of brain vasculature such as the BBB and astrocytic end-feet. Whether pericytes 28 are involved in the control of leukocyte trafficking remains elusive. Using adult, pericyte-29 deficient mice (Pdgfb ret/ret ), we show here that brain vasculature devoid of pericytes shows 30 increased expression of VCAM-1 and ICAM-1, which is accompanied by increased leukocyte 31 infiltration of dendritic cells, monocytes and T cells into the brain, but not spinal cord 32 parenchyma. Regional differences enabling leukocyte trafficking into the brain as opposed to 33 the spinal cord inversely correlate with the pericyte coverage of blood vessels. Upon induction 34 of experimental autoimmune encephalitomyelitis (EAE), pericyte-deficient mice succumb to 35 severe neurological impairment. Treatment with first line MS therapy -fingolimod significantly 36 reverses EAE, indicating that the observed phenotype is due to the massive influx of immune 37 cells into the brain. Furthermore, pericyte-deficiency in mice that express myelin 38 oligodendrocyte glycoprotein peptide (MOG35-55) specific T cell receptor (Pdgfb ret/ret ; 2D2 Tg ) 39 leads to the development of spontaneous neurological symptoms paralleled by massive influx 40 of leukocytes into the brain, suggesting altered brain vascular immune quiescence as a prime 41 cause of exaggerated neuroinflammation. Thus, we show that pericytes indirectly restrict 42 immune cell transmigration into the CNS under homeostatic conditions and during 43 autoimmune-driven neuroinflammation by inducing immune quiescence of brain endothelial 44 cells. 45 46 leukocytes into brain parenchyma, thus contributing to immune privilege of the CNS. BBB 51 function is induced by neural tissue and established by all cell types constituting the 52 neurovascular unit (NVU). Pericytes and mural cells residing on the abluminal side of 53 capillaries and post-capillary venules, regulate several features of the BBB 1, 2 . Studies on Pdgfb 54and Pdgfrb mouse mutants, which exhibit variable pericyte loss, have demonstrated that 55 pericytes negatively regulate endothelial transcytosis which, if not suppressed, leads to 56 increased BBB permeability to plasma proteins 1, 2 . In addition, pericyte-deficient vessels show 57 abnormal astrocyte end-feet polarization 1 . Thus, pericytes regulate several characteristics of 58 brain vasculature during development and in the adult organism 1, 2 . Whether the non-59 permissive properties of brain vasculature to leukocyte traffic...

show abstract

Plastic roles of pericytes in the blood–retinal barrier

Cited by 244 publications

References 73 publications

Methods to label, image, and analyze the complex structural architectures of microvascular networks

Methods to label, image, and analyze the complex structural architectures of microvascular networks

Alpha-Smooth Muscle Actin-Positive Perivascular Cells in Diabetic Retina and Choroid

Pericytes regulate vascular immune homeostasis in the CNS

Contact Info

Product

Resources

About