Pleiotropic and retinoprotective functions of PACAP

Shioda, Seiji; Takenoya, Fumiko; Wada, Nobuhiro; Hirabayashi, Takahiro; Seki, Tamotsu; Nakamachi, Tomoya

doi:10.1007/s12565-016-0351-0

Cited by 48 publications

(37 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study we demonstrated the efficacy of TAT-bound PACAP and VIP peptides to reach the retina and exert a retinoprotective effect in a model of ischemic retinopathy in rats. The retinoprotective effects of PACAP are well-documented in models of many different retinopathies (Atlasz et al 2011 , 2016 ; Shioda et al 2016 ). Intravitreal injections of PACAP have been shown to lead to robust retinoprotective effects in various models of retinal injuries (Atlasz et al 2016 ).…”

Section: Discussionmentioning

confidence: 99%

“…The retinoprotective effects of PACAP are well-documented and have been proven in different injury models, such as excitotoxic, ischemic, UV light-induced, traumatic, diabetic and oxygen-induced injuries (Atlasz et al 2008 , 2011 , 2016 ; Kvarik et al 2016 ; Shioda et al 2016 ; Szabadfi et al 2016 ; Vaczy et al 2016 ). VIP, on the other hand, seems to be a less potent retinoprotective peptide.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Retinoprotective Effects of TAT-Bound Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase Activating Polypeptide

et al. 2018

View full text Add to dashboard Cite

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) belong to the same peptide family and exert a variety of biological functions. Both PACAP and VIP have protective effects in several tissues. While PACAP is known to be a stronger retinoprotective peptide, VIP has very potent anti-inflammatory effects. The need for a non-invasive therapeutic approach has emerged and PACAP has been shown to be retinoprotective when administered in the form of eye drops as well. The cell penetrating peptide TAT is composed of 11 amino acids and tagging of TAT at the C-terminus of neuropeptides PACAP/VIP can enhance the traversing ability of the peptides through the biological barriers. We hypothesized that TAT-bound PACAP and VIP could be more effective in exerting retinoprotective effects when given in eye drops, by increasing the traversing efficacy and enhancing the activation of the PAC1 receptor. Rats were subjected to bilateral carotid artery occlusion (BCCAO), and retinas were processed for histological analysis 14 days later. The efficiency of the TAT-bound peptides to reach the retina was assessed as well as their cAMP increasing ability. Our present study provides evidence, for the first time, that topically administered PACAP and VIP derivatives (PACAP-TAT and VIP-TAT) attenuate ischemic retinal degeneration via the PAC1 receptor presumably due to a multifactorial protective mechanism.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Retinoprotective Effects of TAT-Bound Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase Activating Polypeptide

et al. 2018

View full text Add to dashboard Cite

show abstract

“…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, ). Despite recent findings have revealed that PACAP is able to rescue rat motor neurons against glutamate‐induced excitotoxicity in vitro (Tomimatsu & Arakawa, ), and confers neuroprotection to central visceromotor neurons via autocrine pathways in SOD1(G93A) mice model (Ringer et al, ), the effect of PACAP in ALS still remains unknown.…”

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

View full text Add to dashboard Cite

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.

show abstract

“…PACAP influences the development of the retina [15], and protects against several in vitro and in vivo retinal injuries [16,17,18,19]. In vitro, the peptide has been shown to protect whole retinal tissue cultures [20] and cell cultures from various cell types, including pigment epithelial cells [21,22] and retinal ganglion cells [23].…”

Section: Introductionmentioning

confidence: 99%

Passage through the Ocular Barriers and Beneficial Effects in Retinal Ischemia of Topical Application of PACAP1-38 in Rodents

Werling

Banks

Salameh

et al. 2017

IJMS

View full text Add to dashboard Cite

The neuropeptide pituitary adenylate cyclase activating polypeptide (PACAP) has two active forms, PACAP1-27 and PACAP1-38. Among the well-established actions are PACAP’s neurotrophic and neuroprotective effects, which have also been proven in models of different retinopathies. The route of delivery is usually intravitreal in studies proving PACAP’s retinoprotective effects. Recently, we have shown that PACAP1-27 delivered as eye drops in benzalkonium-chloride was able to cross the ocular barriers and exert retinoprotection in ischemia. Since PACAP1-38 is the dominant form of the naturally occurring PACAP, our aim was to investigate whether the longer form is also able to cross the barriers and exert protective effects in permanent bilateral common carotid artery occlusion (BCCAO), a model of retinal hypoperfusion. Our results show that radioactive PACAP1-38 eye drops could effectively pass through the ocular barriers to reach the retina. Routine histological analysis and immunohistochemical evaluation of the Müller glial cells revealed that PACAP1-38 exerted retinoprotective effects. PACAP1-38 attenuated the damage caused by hypoperfusion, apparent in almost all retinal layers, and it decreased the glial cell overactivation. Overall, our results confirm that PACAP1-38 given in the form of eye drops is a novel protective therapeutic approach to treat retinal diseases.

show abstract

Pleiotropic and retinoprotective functions of PACAP

Cited by 48 publications

References 90 publications

Retinoprotective Effects of TAT-Bound Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase Activating Polypeptide

Retinoprotective Effects of TAT-Bound Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase Activating Polypeptide

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

Passage through the Ocular Barriers and Beneficial Effects in Retinal Ischemia of Topical Application of PACAP1-38 in Rodents

Contact Info

Product

Resources

About