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Restoring retinal neurovascular health via substance P

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Restoring retinal neurovascular health via substance P. / Ou, Kepeng; Mertsch, Sonia; Theodoropoulou, Sofia; Wu, Jiahui; Liu, Jian; Copland, Dave; Schrader, Stefan; Liu, Lei; Dick, Andrew.

In: Experimental Cell Research, Vol. 380, No. 2, 15.07.2019, p. 115-123.

Research output: Contribution to journalArticle

Harvard

Ou, K, Mertsch, S, Theodoropoulou, S, Wu, J, Liu, J, Copland, D, Schrader, S, Liu, L & Dick, A 2019, 'Restoring retinal neurovascular health via substance P', Experimental Cell Research, vol. 380, no. 2, pp. 115-123. https://doi.org/10.1016/j.yexcr.2019.04.008

APA

Ou, K., Mertsch, S., Theodoropoulou, S., Wu, J., Liu, J., Copland, D., ... Dick, A. (2019). Restoring retinal neurovascular health via substance P. Experimental Cell Research, 380(2), 115-123. https://doi.org/10.1016/j.yexcr.2019.04.008

Vancouver

Ou K, Mertsch S, Theodoropoulou S, Wu J, Liu J, Copland D et al. Restoring retinal neurovascular health via substance P. Experimental Cell Research. 2019 Jul 15;380(2):115-123. https://doi.org/10.1016/j.yexcr.2019.04.008

Author

Ou, Kepeng ; Mertsch, Sonia ; Theodoropoulou, Sofia ; Wu, Jiahui ; Liu, Jian ; Copland, Dave ; Schrader, Stefan ; Liu, Lei ; Dick, Andrew. / Restoring retinal neurovascular health via substance P. In: Experimental Cell Research. 2019 ; Vol. 380, No. 2. pp. 115-123.

Bibtex

@article{8da7c5a42eae49ef9b142f797cb329c6,
title = "Restoring retinal neurovascular health via substance P",
abstract = "Regulation of vascular permeability plays a major role in the pathophysiology of visually threatening conditions such as retinal vein occlusion and diabetic retinopathy. Principally, several factors such as vascular endothelial growth factor (VEGF), are up-regulated or induced in response to hypoxia thus adversely affecting the blood-retinal barrier (BRB), resulting in retinal edema and neovascularisation. Furthermore, current evidence supports a dysregulation of the inner retinal neural-vascular integrity as a critical factor driving retinal ganglion cell (RGC) death and visual loss. The principal objective of this study was to interrogate whether Substance P (SP), a constitutive neurotransmitter of amacrine and ganglion cells, may protect against N-methyl-d-aspartate (NMDA)-induced excitotoxic apoptosis of ganglion cells and VEGF-induced vessel leakage in the retina. Tight junctional protein expression and a Vascular Permeability Image Assay were used to determine vascular integrity in vitro. The protective effect of SP on RGC was established in ex vivo retinal explants and in vivo murine models. After NMDA administration, a reduction in TUNEL+ cells and a maintained number of Brn-3a+ cells were found, indicating an inhibition of RGC apoptosis mediated by SP. Additionally, SP maintained endothelial tight junctions and decreased VEGF-induced vascular permeability. In conclusion, administration of SP protects against NMDA apoptosis of RGC and VEGF-induced endothelial barrier breakdown.",
keywords = "Substance P, Retinal ganglion cell, Vascular permeability, ZO-1",
author = "Kepeng Ou and Sonia Mertsch and Sofia Theodoropoulou and Jiahui Wu and Jian Liu and Dave Copland and Stefan Schrader and Lei Liu and Andrew Dick",
year = "2019",
month = "7",
day = "15",
doi = "10.1016/j.yexcr.2019.04.008",
language = "English",
volume = "380",
pages = "115--123",
journal = "Experimental Cell Research",
issn = "0014-4827",
publisher = "Academic Press",
number = "2",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Restoring retinal neurovascular health via substance P

AU - Ou, Kepeng

AU - Mertsch, Sonia

AU - Theodoropoulou, Sofia

AU - Wu, Jiahui

AU - Liu, Jian

AU - Copland, Dave

AU - Schrader, Stefan

AU - Liu, Lei

AU - Dick, Andrew

PY - 2019/7/15

Y1 - 2019/7/15

N2 - Regulation of vascular permeability plays a major role in the pathophysiology of visually threatening conditions such as retinal vein occlusion and diabetic retinopathy. Principally, several factors such as vascular endothelial growth factor (VEGF), are up-regulated or induced in response to hypoxia thus adversely affecting the blood-retinal barrier (BRB), resulting in retinal edema and neovascularisation. Furthermore, current evidence supports a dysregulation of the inner retinal neural-vascular integrity as a critical factor driving retinal ganglion cell (RGC) death and visual loss. The principal objective of this study was to interrogate whether Substance P (SP), a constitutive neurotransmitter of amacrine and ganglion cells, may protect against N-methyl-d-aspartate (NMDA)-induced excitotoxic apoptosis of ganglion cells and VEGF-induced vessel leakage in the retina. Tight junctional protein expression and a Vascular Permeability Image Assay were used to determine vascular integrity in vitro. The protective effect of SP on RGC was established in ex vivo retinal explants and in vivo murine models. After NMDA administration, a reduction in TUNEL+ cells and a maintained number of Brn-3a+ cells were found, indicating an inhibition of RGC apoptosis mediated by SP. Additionally, SP maintained endothelial tight junctions and decreased VEGF-induced vascular permeability. In conclusion, administration of SP protects against NMDA apoptosis of RGC and VEGF-induced endothelial barrier breakdown.

AB - Regulation of vascular permeability plays a major role in the pathophysiology of visually threatening conditions such as retinal vein occlusion and diabetic retinopathy. Principally, several factors such as vascular endothelial growth factor (VEGF), are up-regulated or induced in response to hypoxia thus adversely affecting the blood-retinal barrier (BRB), resulting in retinal edema and neovascularisation. Furthermore, current evidence supports a dysregulation of the inner retinal neural-vascular integrity as a critical factor driving retinal ganglion cell (RGC) death and visual loss. The principal objective of this study was to interrogate whether Substance P (SP), a constitutive neurotransmitter of amacrine and ganglion cells, may protect against N-methyl-d-aspartate (NMDA)-induced excitotoxic apoptosis of ganglion cells and VEGF-induced vessel leakage in the retina. Tight junctional protein expression and a Vascular Permeability Image Assay were used to determine vascular integrity in vitro. The protective effect of SP on RGC was established in ex vivo retinal explants and in vivo murine models. After NMDA administration, a reduction in TUNEL+ cells and a maintained number of Brn-3a+ cells were found, indicating an inhibition of RGC apoptosis mediated by SP. Additionally, SP maintained endothelial tight junctions and decreased VEGF-induced vascular permeability. In conclusion, administration of SP protects against NMDA apoptosis of RGC and VEGF-induced endothelial barrier breakdown.

KW - Substance P

KW - Retinal ganglion cell

KW - Vascular permeability

KW - ZO-1

UR - http://www.scopus.com/inward/record.url?scp=85064195962&partnerID=8YFLogxK

U2 - 10.1016/j.yexcr.2019.04.008

DO - 10.1016/j.yexcr.2019.04.008

M3 - Article

VL - 380

SP - 115

EP - 123

JO - Experimental Cell Research

JF - Experimental Cell Research

SN - 0014-4827

IS - 2

ER -