Restoring retinal neurovascular health via substance P.

Authors:
Kepeng Ou
Kepeng Ou
Bristol Heart Institute
Bristol | United Kingdom
Sonja Mertsch
Sonja Mertsch
Institute of Neuropathology
Germany
Sofia Theodoropoulou
Sofia Theodoropoulou
University of Athens
Greece
Jiahui Wu
Jiahui Wu
University of Alberta
Edmonton | Canada
Dr Jian Liu, PhD
Dr Jian Liu, PhD
Curtin University
Senior Lecturer
Nanoporous materials
Perth, WA | Australia
David A Copland
David A Copland
The University of Queensland
Australia
Stefan Schrader
Stefan Schrader
UCL Institute of Ophthalmology
Lei Liu
Lei Liu
Sichuan University
China

Exp Cell Res 2019 Jul 14;380(2):115-123. Epub 2019 Apr 14.

Academic Unit of Ophthalmology, Bristol Medical School, University of Bristol, Bristol, UK; National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London, UK. Electronic address:

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.

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Source
https://linkinghub.elsevier.com/retrieve/pii/S00144827193015
Publisher Site
http://dx.doi.org/10.1016/j.yexcr.2019.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548993PMC
July 2019
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