Blood-retinal barrier protection against high glucose damage: The role of P2X7 receptor

Platania, Chiara Bianca Maria; Lazzara, Francesca; Fidilio, Annamaria; Fresta, Claudia G.; Conti, Federica; Giurdanella, Giovanni; Leggio, Gian Marco; Salomone, Salvatore; Drago, Filippo; Bucolo, Claudio

doi:10.1016/j.bcp.2019.07.010

Cited by 43 publications

(45 citation statements)

References 49 publications

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“…The loss of pericytes has been associated with microcirculation damage and inflammation processes[ 11 , 12 ], such as those occurring in diabetic retinopathy (DR). Loss of pericytes is one of the earliest hallmarks of DR[ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Pericyte-like differentiation of human adipose-derived mesenchymal stem cells: An in vitro study

Mannino

Gennuso

Giurdanella

et al. 2020

WJSC

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BACKGROUND Adipose-derived mesenchymal stem cells (ASCs) are characterized by long-term self-renewal and a high proliferation rate. Under adequate conditions, they may differentiate into cells belonging to mesodermal, endodermal or ectodermal lineages. Pericytes support endothelial cells and play an important role in stabilizing the vessel wall at the microcirculation level. The loss of pericytes, as occurs in diabetic retinopathy, results in a breakdown of the blood-retina barrier (BRB) and infiltration of inflammatory cells. In this context, the use of pericyte-like differentiated ASCs may represent a valuable therapeutic strategy for restoring BRB damage. AIM To test in vitro strategies to obtain pericyte-like differentiation of human ASCs (hASCs). METHODS Different culture conditions were tested: hASCs cultured in a basal medium supplemented with transforming growth factor β1; and hASCs cultured in a specific pericyte medium (PM-hASCs). In a further sample, pericyte growth supplement was omitted from the PM. In addition, cultures of human retinal pericytes (hRPCs) were used for comparison. Pericyte-like differentiation of hASCs was tested by immunocytochemical staining and western blotting to evaluate the expression of α-smooth muscle actin (α-SMA) and neural/glial antigen 2 (NG2). Interactions between human retinal endothelial cells (hRECs) and different groups of hASCs were investigated in co-culture experiments. In these cases, the expression of typical junctional proteins such as vascular endothelial-Cadherin, zonula occludens-1 and Occludin were assessed in hRECs. In an in vitro model of the BRB, values of trans-endothelial electrical resistance were measured when hRECs were co-cultured with various groups of pretreated hASCs. The values observed were compared with co-cultures of hRECs and hRPCs as well as with cultures of hRECs alone. Three-dimensional co-cultures of hRECs and hRPCs or pericyte-like hASCs in Matrigel were designed to assess their reciprocal localization. RESULTS After 3-6 d of culture, α-SMA and NG2 immunocytochemistry showed that the closest pericyte-like phenotype was observed when hASCs were cultured in Pericyte Medium (PM-hASCs). In particular, α-SMA immunoreactivity, already visible at the basal level in pericytes and ASCs, was strongly increased only when transforming growth factor was added to the culture medium. NG2 expression, almost undetectable in most conditions, was substantially increased only in PM-hASCs. Immunocytochemical results were confirmed by western blot analysis. The presence of pericyte growth supplement seems to increase NG2 expression rather than α-SMA, in agreement with its role in maintaining pericytes in the proliferative state. In co-culture experiments, immunoreactivity of vascular endothelial-Cadherin, zonula occludens-1 and Occludin was considerably increased in hRECs when hRPCs or PM-hASCs were a...

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Section: Introductionmentioning

confidence: 99%

Pericyte-like differentiation of human adipose-derived mesenchymal stem cells: An in vitro study

Mannino

Gennuso

Giurdanella

et al. 2020

WJSC

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“…It is well established that inflammation contributes to DR development and progression [7][8][9][10][11][12]. Recent computational analyses of microarray datasets have demonstrated that the pathogenesis of DR is linked to inflammation and fibrosis [8].…”

Section: Introductionmentioning

confidence: 99%

“…Increased production of proinflammatory cytokines, such as IL-1, TNF-α and VEGF, have been reported in the vitreous of DR patients and in the retinas of DR animal models [7,9]. High-glucose-induced upregulation of proinflammatory cytokines can cause breakdown of the blood-retinal barrier (BRB), cell death and angiogenesis [7,10]. VEGF-A is the major angiogenic factor and contributes to the pathogenesis of diabetic macular edema [7].…”

Section: Introductionmentioning

confidence: 99%

Protection by vitamin D against high-glucose-induced damage in retinal pigment epithelial cells

Tohari

Almarhoun

Alhasani

et al. 2020

Experimental Cell Research

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Diabetic retinopathy (DR) is a diabetes-associated complication characterized by irreversible deterioration of the microvessels within the retina, leading subsequently to severe retinal damage and vision loss. Vitamin D (VITD), a steroid hormone, plays multiple physiological functions in cellular homeostasis. Deficiency of VITD has been suggested to be associated with DR. To study the potential protective function of VITD in DR, high-glucose-treated ARPE-19 cells and STZ-induced diabetic mice were used as in vitro and in vivo models. The protective effects of VITD were assessed based on the changes of expression of antioxidant enzymes and cytokines in high-glucose-treated RPE cells and in the retina and retinal pigment epithelium (RPE) of diabetic and VITD-treated diabetic mice. The present study demonstrated that exposure to a high level of glucose caused upregulation of pro-inflammatory cytokines and a decrease in anti-oxidant enzyme expression in both in vitro and in vivo models. VITD treatment increased cell viability, reduced reactive oxygen species (ROS) production and caspase-3/7 activities in high-glucose-treated RPE cells. Our data suggest that VITD can protect the retina and RPE from high-glucose-induced oxidative damage and inflammation.

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“…These ATP effects were abrogated by P2X7 receptor antagonist, suggesting that they were P2X7 receptor-dependent. Similarly, hyperglycaemia induced the production of IL-1β via P2X7 receptor activation and caused damage to the retinal endothelial cell-cell junctions and barrier that was abrogated by a selective P2X7 receptor antagonist [118]. Likewise, in an in vivo model of intracranial haemorrhage, an upregulation of P2X7 receptor expression accompanied by the development of cranial oedema was observed.…”

Section: P2x Receptors and Endothelial Barriermentioning

confidence: 96%

Purinergic Regulation of Endothelial Barrier Function

Aslam

Gündüz

Troidl

et al. 2021

IJMS

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Increased vascular permeability is a hallmark of several cardiovascular anomalies, including ischaemia/reperfusion injury and inflammation. During both ischaemia/reperfusion and inflammation, massive amounts of various nucleotides, particularly adenosine 5′-triphosphate (ATP) and adenosine, are released that can induce a plethora of signalling pathways via activation of several purinergic receptors and may affect endothelial barrier properties. The nature of the effects on endothelial barrier function may depend on the prevalence and type of purinergic receptors activated in a particular tissue. In this review, we discuss the influence of the activation of various purinergic receptors and downstream signalling pathways on vascular permeability during pathological conditions.

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Blood-retinal barrier protection against high glucose damage: The role of P2X7 receptor

Cited by 43 publications

References 49 publications

Pericyte-like differentiation of human adipose-derived mesenchymal stem cells: An in vitro study

Pericyte-like differentiation of human adipose-derived mesenchymal stem cells: An in vitro study

Protection by vitamin D against high-glucose-induced damage in retinal pigment epithelial cells

Purinergic Regulation of Endothelial Barrier Function

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