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Treatment of diabetic retinopathy through neuropeptide Y-mediated enhancement of neurovascular microenvironment.
- Source :
-
Journal of cellular and molecular medicine [J Cell Mol Med] 2020 Apr; Vol. 24 (7), pp. 3958-3970. Date of Electronic Publication: 2020 Mar 06. - Publication Year :
- 2020
-
Abstract
- Diabetic retinopathy (DR) is one of the most severe clinical manifestations of diabetes mellitus and a major cause of blindness. DR is principally a microvascular disease, although the pathogenesis also involves metabolic reactive intermediates which induce neuronal and glial activation resulting in disruption of the neurovascular unit and regulation of the microvasculature. However, the impact of neural/glial activation in DR remains controversial, notwithstanding our understanding as to when neural/glial activation occurs in the course of disease. The objective of this study was to determine a potential protective role of neuropeptide Y (NPY) using an established model of DR permissive to N-methyl-D-aspartate (NMDA)-induced excitotoxic apoptosis of retinal ganglion cells (RGC) and vascular endothelial growth factor (VEGF)-induced vascular leakage. In vitro evaluation using primary retinal endothelial cells demonstrates that NPY promotes vascular integrity, demonstrated by maintained tight junction protein expression and reduced permeability in response to VEGF treatment. Furthermore, ex vivo assessment of retinal tissue explants shows that NPY can protect RGC from excitotoxic-induced apoptosis. In vivo clinical imaging and ex vivo tissue analysis in the diabetic model permitted assessment of NPY treatment in relation to neural and endothelial changes. The neuroprotective effects of NPY were confirmed by attenuating NMDA-induced retinal neural apoptosis and able to maintain inner retinal vascular integrity. These findings could have important clinical implications and offer novel therapeutic approaches for the treatment in the early stages of DR.<br /> (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
- Subjects :
- Animals
Apoptosis drug effects
Cellular Microenvironment drug effects
Diabetes Mellitus, Experimental drug therapy
Diabetes Mellitus, Experimental genetics
Diabetes Mellitus, Experimental pathology
Diabetic Retinopathy genetics
Diabetic Retinopathy pathology
Endothelial Cells drug effects
Humans
Mice
N-Methylaspartate pharmacology
Neuropeptide Y genetics
Rats
Retina drug effects
Retina pathology
Retinal Ganglion Cells drug effects
Retinal Ganglion Cells pathology
Retinal Neovascularization genetics
Retinal Neovascularization pathology
Vascular Endothelial Growth Factor A pharmacology
Diabetic Retinopathy drug therapy
N-Methylaspartate genetics
Neuropeptide Y pharmacology
Retinal Neovascularization drug therapy
Vascular Endothelial Growth Factor A genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1582-4934
- Volume :
- 24
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of cellular and molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 32141716
- Full Text :
- https://doi.org/10.1111/jcmm.15016