Impact of type 1 diabetes mellitus and sitagliptin treatment on the neuropeptide Y system of rat retina

Campos, Elisa J.; Martins, João; Brudzewsky, Dan; Correia, Sandra; Santiago, Ana Raquel; Woldbye, David P.D.; Ambrósio, António Francisco

doi:10.1111/ceo.13176

Cited by 3 publications

(4 citation statements)

References 44 publications

(116 reference statements)

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“…The study by Christiansen demonstrates that NPY has a detrimental effect in ischaemic retina, a model induced by acutely raising intraocular pressure and restricting ocular perfusion. However, in diabetic retinas (and seen in the STZ model) more insidious pathophysiological changes are observed, which show reduced NPY (gene and protein) expression in the mouse retina, more relevant to human diabetes, and emphasize the importance of the context and how the results are interpreted. In the current study, our approach was to investigate the adjunctive effect of extracellular NPY as a therapy to restore homeostasis, opposed to an association with a specific SNP in the NPY gene that may indicate causality in DR.…”

Section: Discussionmentioning

confidence: 99%

“…In light of the reported decrease in mRNA and protein levels for NPY in diabetic retina, as well as observations of NPY function, we examined whether administration of NPY would extend and offer protection of the neurovascular multicellular complex in the diabetic retina. Using in vitro platforms, we first assessed whether neuroprotective actions of NPY could reduce the sensitivity of retinal neurons to glutamate‐induced excitotoxicity.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of diabetic retinopathy through neuropeptide Y‐mediated enhancement of neurovascular microenvironment

Copland

Theodoropoulou

et al. 2020

J Cellular Molecular Medi

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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. K E Y W O R D S diabetic retinopathy, neurovascular unit, NPY, retinal ganglion cells, vascular permeability, ZO-1 | 3959 OU et al. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section. How to cite this article: Ou K, Copland DA, Theodoropoulou S, et al. Treatment of diabetic retinopathy through neuropeptide Y-mediated enhancement of neurovascular microenvironment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Treatment of diabetic retinopathy through neuropeptide Y‐mediated enhancement of neurovascular microenvironment

Copland

Theodoropoulou

et al. 2020

J Cellular Molecular Medi

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“…It was suggested that activated microglia contributed to the pathology of HD, and microglial activation was likely to increase over the course of the disease using [11C] (R)-PK11195 PET ([11C] raclopride positron emission computed tomography, a marker for dopamine D2 receptor binding) as an in vivo marker for activated microglia (Hansen et al, 2018). The distribution of NPY in retinal and cortical macroglial as well as the levels of NPY and the number of Y1 receptors were increased upon microglial activation (Li et al, 2014; Thorsell and Mathe, 2017; Campos et al, 2018). Increasing evidence was found to support the role of NPY in modulating microglial inflammatory responses (Ferreira et al, 2011, 2012).…”

Section: Roles Of Npy In Neurodegenerative Diseasesmentioning

confidence: 99%

Roles of Neuropeptide Y in Neurodegenerative and Neuroimmune Diseases

Liu

et al. 2019

Front. Neurosci.

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Neuropeptide Y (NPY) is a neurotransmitter or neuromodulator that mainly exists in the nervous system. It plays a neuroprotective role in organisms and widely participates in the regulation of various physiological processes in vivo . Studies in both humans and animal models have been revealed that NPY levels are altered in some neurodegenerative and neuroimmune disorders. NPY plays various roles in these diseases, such as exerting a neuroprotective effect, increasing trophic support, decreasing excitotoxicity, regulating calcium homeostasis, and attenuating neuroinflammation. In this review, we will focus on the roles of NPY in the pathological mechanisms of neurodegenerative and neuroimmune diseases, highlighting NPY as a potential therapeutic target in these diseases.

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“…The induction of diabetes in rats (as in STZ-treated animals) decreased the retinal NPY mRNA levels, as well as the protein levels of NPY and of NPY Y 5 receptor [91]. Of interest, NPY was demonstrated a neuroprotective agent against necrotic and apoptotic cell death induced by cytotoxic glutamate in rat retinal cells both in vitro and in vivo.…”

Section: Neuropeptide Ymentioning

confidence: 99%

Neuroprotective Peptides in Retinal Disease

Cervia

Catalani

Casini

2019

JCM

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In the pathogenesis of many disorders, neuronal death plays a key role. It is now assumed that neurodegeneration is caused by multiple and somewhat converging/overlapping death mechanisms, and that neurons are sensitive to unique death styles. In this respect, major advances in the knowledge of different types, mechanisms, and roles of neurodegeneration are crucial to restore the neuronal functions involved in neuroprotection. Several novel concepts have emerged recently, suggesting that the modulation of the neuropeptide system may provide an entirely new set of pharmacological approaches. Neuropeptides and their receptors are expressed widely in mammalian retinas, where they exert neuromodulatory functions including the processing of visual information. In multiple models of retinal diseases, different peptidergic substances play neuroprotective actions. Herein, we describe the novel advances on the protective roles of neuropeptides in the retina. In particular, we focus on the mechanisms by which peptides affect neuronal death/survival and the vascular lesions commonly associated with retinal neurodegenerative pathologies. The goal is to highlight the therapeutic potential of neuropeptide systems as neuroprotectants in retinal diseases.

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Impact of type 1 diabetes mellitus and sitagliptin treatment on the neuropeptide Y system of rat retina

Abstract: DM modestly affects the NPY system in the retina and these effects are not prevented by sitagliptin treatment. These observations suggest that DPP-IV enzyme is not underlying the NPY changes detected in the retina induced by type 1 DM.

Cited by 3 publications

References 44 publications

Treatment of diabetic retinopathy through neuropeptide Y‐mediated enhancement of neurovascular microenvironment

Treatment of diabetic retinopathy through neuropeptide Y‐mediated enhancement of neurovascular microenvironment

Roles of Neuropeptide Y in Neurodegenerative and Neuroimmune Diseases

Neuroprotective Peptides in Retinal Disease

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