VIP Family Members Prevent Outer Blood Retinal Barrier Damage in a Model of Diabetic Macular Edema

Maugeri, Grazia; D’Amico, Agata Grazia; Gagliano, Caterina; Saccone, Salvatore; Federico, Concetta; Cavallaro, Sebastiano; D’Agata, Velia

doi:10.1002/jcp.25510

Cited by 39 publications

(35 citation statements)

References 37 publications

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“…As previously demonstrated, the barrier breakdown is correlated to increased cellular death induced by the combinatorial action of hyperglycemia and hypoxia [He et al, ; Maugeri et al, ,]. Caffeine's role on programmed cell death seems ambiguous.…”

Section: Discussionmentioning

confidence: 95%

“…Cells were treated with 25 mM glucose (HG) in the presence or absence of 100 μM DFX (HG+DFX), alone or in combination with caffeine for 24 h. The typical morphological features of apoptotic degeneration were analyzed by the use of confocal microscopy with the nuclear dye Hoechst 33342 as previously described by Maugeri et al (). Cells were fixed with a solution of methanol/acetic acid (3:1 v/v) for 30 min, washed three times in PBS, and incubated for 15 min at 37°C with 0,4 μg/ml Hoechst 33342 dye.…”

Section: Methodsmentioning

confidence: 99%

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Caffeine Prevents Blood Retinal Barrier Damage in a Model, In Vitro, of Diabetic Macular Edema

et al. 2017

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Diabetic macular edema (DME) is the major cause of vision loss in patients affected by diabetic retinopathy. Hyperglycemia and hypoxia represent the key elements in the progression of these pathologies, leading to breakdown of the blood-retinal barrier (BRB). Caffeine, a psychoactive substance largely consumed in the world, is a nonselective antagonist of adenosine receptors (AR) and it possesses a protective effect in various diseases, including eye pathologies. Here, we have investigated the effect of this substance on BRB integrity following exposure to hyperglycemic/hypoxic insult. Retinal pigmented epithelial cells, ARPE-19, have been grown on semi-permeable supports mimicking an experimental model, in vitro, of outer BRB. Caffeine treatment has reduced cell monolayer permeability after exposure to high glucose and desferoxamine as shown by TEER and FITC-dextran permeability assays. This effect is also mediated through the restoration of membrane's tight junction expression, ZO-1. Moreover, we have demonstrated that caffeine is able to prevent outer BRB damage by inhibiting apoptotic cell death induced by hyperglycemic/hypoxic insult since it downregulates the proapoptotic Bax and upregulates the anti-apoptotic Bcl-2 genes. Although further studies are needed to better comprise the beneficial effect of caffeine, we can speculate that it might be used as an innovative drug for DME treatment. J. Cell. Biochem. 118: 2371-2379, 2017. © 2017 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

Caffeine Prevents Blood Retinal Barrier Damage in a Model, In Vitro, of Diabetic Macular Edema

et al. 2017

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“…Different papers have suggested that PACAP and VIP through the binding to three G‐protein coupled receptors, perform a protective role against several types of retinal injuries, including DME, which is the leading cause of blindness in the diabetic population (Yonekura et al, ). In our recent paper, we have demonstrated that these peptides through the interaction with their own receptors prevent the damage to the outer BRB by activating two protective signaling pathways: the PI3K/Akt and the MAPK/ERK (Maugeri et al, ). In the present study, we have furtherly deepened the characterization of the mechanism exerted by these peptides on RPE, when this latter is exposed to the hyperglycemia/hypoxia insult, a condition mimicking tightly the microenvironment which triggers the DME pathology.…”

Section: Discussionmentioning

confidence: 99%

PACAP and VIP Inhibit HIF‐1α‐Mediated VEGF Expression in a Model of Diabetic Macular Edema

Maugeri

D’Amico

Saccone

et al. 2016

Journal Cellular Physiology

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Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) exert a protective role against retinal injuries, including diabetic macular edema (DME). The macular damage is induced by hyperglycemia, which damages vessels supplying blood to the retina and induces hypoxia. The microenvironmental changes stimulate the expression of hypoxia-inducible factors (HIFs), which promote the choroidal endothelial cell transmigration across the retinal pigmented epithelium (RPE) into neurosensory retina, where they proliferate into new vessels under stimulation of the vascular endothelial growth factor (VEGF). In the present study, we have investigated whether PACAP and VIP prevent retinal damage by modulating the expression of HIFs, VEGF, and its receptors. In accord to our hypothesis, we have shown that both peptides are able to significantly reduce HIF-1α and increase HIF-3α expression in ARPE-19 cells exposed to hyperglycemic/hypoxic insult. This effect is also related to a reduction of VEGF and its receptors expression. Moreover, both peptides also reduce the activation of p38 mitogen-activated protein kinase (MAPK), a pro-apoptotic signaling pathway, which is activated by VEGFR-1 and 2 receptors. In conclusion, our study has further elucidated the protective role performed by PACAP and VIP, against the harmful combined effect of hyperglycemia/hypoxia characterizing the DME microenvironment. J. Cell. Physiol. 232: 1209-1215, 2017. © 2016 Wiley Periodicals, Inc.

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“…Most of its effects are mediated through the activation of PAC1R, whereas others are due to VPAC1 or VPAC2 receptors, which bind also VIP (Arimura, ; Arimura & Shioda, ; Zhou et al, ). PACAP is a pleiotropic molecule, involved in a wide range of physiological processes, including cell survival during neurodegenerative conditions, stress response and cell division (Canonico et al, ; Castorina et al, ; Castorina, Giunta, Mazzone, Cardile, & D'Agata, ; Castorina, Scuderi, D'Amico, Drago, & D'Agata, ; Cavallaro et al, , ; D'Agata & Cavallaro, ; D'Agata, Cavallaro, Stivala, Travali, & Canonico, ; D'Amico et al, , ; Giunta et al, ; Maino et al, ; Maugeri, D'Amico, & Gagliano, ; Maugeri, D'Amico, & Saccone, ; Scuderi et al, ). Moreover, it is known to act as a neurotransmitter and/or a neuromodulator in the peripheral and central nervous system (Jóźwiak‐Bębenista, Kowalczyk, & Nowak, ; Shioda et al, , ; Yang et al, ).…”

Section: Introductionmentioning

confidence: 99%

PACAP and PAC1R are differentially expressed in motor cortex of amyotrophic lateral sclerosis patients and support survival of iPSC‐derived motor neurons

Bonaventura

Iemmolo

D’Amico

et al. 2017

Journal Cellular Physiology

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Amyotrophic lateral sclerosis (ALS) is a fatal and disabling neurodegenerative disease characterized by upper and lower motor neurons depletion. In our previous work, comprehensive genomic profiling of 41 motor cortex samples enabled to discriminate controls from sporadic ALS patients, and segregated these latter into two distinct subgroups (SALS1 and SALS2), each associated with different deregulated genes. In the present study, we focused our attention on two of them, Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) and its type 1 receptor (PAC1R), and validated the results of the transcriptome experiments by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), immunohistochemistry and Western blot analysis. To assess the functional role of PACAP and PAC1R in ALS, we developed an in vitro model of human induced pluripotent stem cells (iPSC)-derived motor neurons and examined the trophic effects of exogenous PACAP following neurodegenerative stimuli. Treatment with 100 nm PACAP was able to effectively rescue iPSC-derived motor neurons from apoptosis, as shown by cell viability assay and protein dosage of the apoptotic marker (BAX). All together, these data suggest that perturbations in the PACAP-PAC1R pathway may be involved in ALS pathology and represent a potential drug target to enhance motor neuron viability.

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VIP Family Members Prevent Outer Blood Retinal Barrier Damage in a Model of Diabetic Macular Edema

Cited by 39 publications

References 37 publications

Caffeine Prevents Blood Retinal Barrier Damage in a Model, In Vitro, of Diabetic Macular Edema

Caffeine Prevents Blood Retinal Barrier Damage in a Model, In Vitro, of Diabetic Macular Edema

PACAP and VIP Inhibit HIF‐1α‐Mediated VEGF Expression in a Model of Diabetic Macular Edema

PACAP and PAC1R are differentially expressed in motor cortex of amyotrophic lateral sclerosis patients and support survival of iPSC‐derived motor neurons

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