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Anatomical Science International

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20.06.2016 | Review Article

Pleiotropic and retinoprotective functions of PACAP

verfasst von: Seiji Shioda, Fumiko Takenoya, Nobuhiro Wada, Takahiro Hirabayashi, Tamotsu Seki, Tomoya Nakamachi

Erschienen in: Anatomical Science International | Ausgabe 4/2016

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Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a 27- or 38-amino acid neuropeptide, which belongs to the vasoactive intestinal polypeptide/glucagon/secretin family. PACAP and its three receptor subtypes are expressed in neural tissues of the eye, including the retina, cornea and lacrimal gland, and PACAP is known to exert pleiotropic effects throughout the central nervous system. This review provides an overview of current knowledge regarding the cell protective effects, mechanisms of action and therapeutic potential of PACAP in response to several types of eye injury.

Arimura A (1992) Pituitary adenylate cyclase activating polypeptide (PACAP): discovery and current status of research. Regul Pept 37:287–303PubMed

Arimura A, Shioda S (1995) Pituitary adenylate cyclase activating polypeptide (PACAP) and its receptors: neuroendocrine and endocrine interactions. Front Neuroendocrinol 16:53–88CrossRefPubMed

Asghar MS, Hansen AE, Amin FM et al (2011) Evidence for a vascular factor in migraine. Ann Neurol 69:635–645CrossRefPubMed

Atlasz T, Szabadfi K, Kiss P et al (2008) PACAP-mediated neuroprotection of neurochemically identified cell types in MSG-induced retinal degeneration. J Mol Neurosci 36:97–104CrossRefPubMed

Atlasz T, Szabadfi K, Kiss P et al (2010) Evaluation of the protective effects of PACAP with cell-specific markers in ischemia-induced retinal degeneration. Brain Res Bull 81:497–504CrossRefPubMed

Atlasz T, Szabadfi K, Kiss P et al (2011) Effects of PACAP in UV-A radiation-induced retinal degeneration models in rats. J Mol Neurosci 43:51–57CrossRefPubMed

Babai N, Atlasz T, Tamas A et al (2005) Degree of damage compensation by various PACAP treatments in monosodium glutamate-induced retinal degeneration. Neurotox Res 8:227–233CrossRefPubMed

Bangnoli P, Dal Monte M, Casini G (2003) Expression of neuropeptides and their receptors in the developing retina of mammals. Histol Histopathol 18:1219–1242

Banks WA, Kastin AJ, Komaki G, Arimura A (1993) Passage of pituitary adenylate cyclase activating polypeptide1-27 and pituitary adenylate cyclase activating polypeptide1-38 across the blood-brain barrier. J Pharmacol Exp Ther 267:690–696PubMed

Banks WA, Uchida D, Arimura A, Somogyvari-Vigh A, Shioda S (1996) Transport of pituitary adenylate cyclase-activating polypeptide across the blood-brain barrier and the prevention of ischemia-induced death of hippocampal neurons. Ann NY Acad Sci 805:270–277CrossRefPubMed

Birk S, Sitarz JT, Petersen KA et al (2007) The effect of intravenous PACAP38 on cerebral hemodynamics in healthy volunteers. Regul Pept 140:185–191CrossRefPubMed

Boni LJ, Ploug KB, Olesen J, Jansen-Olesen I, Gupta S (2009) The in vivo effect of VIP, PACAP-38 and PACAP-27 and mRNA expression of their receptors in rat middle meningeal artery. Cephalalgia 29:837–847CrossRefPubMed

Borba JC, Henze IP, Silveira MS et al (2005) Pituitary adenylate cyclase-activating polypeptide (PACAP) can act as deteminant of the tyrosine hydroxylase phenotype of dopaminergic cells during retina development. Brain Res Dev Brain Res 156:193–201CrossRefPubMed

Boyd ZS, Kriatchko A, Yang J, Agarwal N, Wax MB, Patil RV (2003) Interleukin-10 receptor signaling through STAT-3 regulates the apoptosis of retinal ganglion cells in response to stress. Invest Ophthalmol Vis Sci 44:5206–5211CrossRefPubMed

Colton CA (2009) Heterogeneity of microglial activation in the innate immune response in the brain. J Neuroimmune Pharmacol 4:399–418CrossRefPubMedPubMedCentral

D’Agata V, Cavallaro S (1998) Functional and molecular expression of PACAP/VIP receptors in the rat retina. Brain Res Mol Brain Res 54:161–164CrossRefPubMed

D’Alessandrom A, Cerivia D, Catalanni E, Gevi F, Zolla L, Casini G (2014) Protective effects of the neuropeptides PACAP, substance P and the somatostatin analogue octreotide in retinal ischemia: a metabolomic analysis. Mol Biosystem 10:1290–1304CrossRef

Danyadi B, Szabadfi K, Reglodi D et al (2014) PACAP application improves functional outcome of chronic retinal ischemic injury in rats—evidence from electroretinographic measurements. J Mol Neurosci 54:293–299CrossRefPubMed

Ding Y, Cheng H, Yu R, Tang C, Liu X, Chen J (2012) Effects of cyclopeptide C*HSDGIC* from the cyclization of PACAP (1–5) on the proliferation and UVB-induced apoptosis of the retinal ganglion cell line RGC-5. Peptides 36:280–285CrossRefPubMed

Drago F, Valzelli S, Emmi I, Marino A, Scalia CC, Marino V (2001) Latanoprost exerts neuroprotective activity in vitro and in vivo. Surv Opthalmol Suppl 1:S162–S175

Elsas T, Uddman R, Sundler F (1996) Pituitary adenylate cyclase-activating peptide immunoreactive nerve fibers in the cat eye. Graefes Arch Clin Opthalmol 234:573–580CrossRef

Endo K, Nakamachi T, Seki T et al (2011) Neuroprotective effect of PACAP against NMDA-induced retinal damage in the mouse. J Mol Neurosci 43:22–29CrossRefPubMed

Fabian E, Reglodi D, Mester L et al (2012) Effects of PACAP on intracellular signaling pathways in human retinal pigment epithelia cells exposed to oxidative stress. J Mol Neurosci 48:493–500CrossRefPubMed

Gaal V, Mark L, Kiss P et al (2008) Investigation of the effects of PACAP on the composition of tear and endolymph proteins. J Mol Neurosci 36:321–329CrossRefPubMed

Gordon S, Taylor PR (2005) Monocyte and macrophage heterogeneity. Nat Rev Immunol 5:953–964CrossRefPubMed

Grone BP, Zhao S, Chen CC, Fernald RD (2007) Localization and diurnal expression of melanopsin, vertebrate ancient opsin, and pituitary adenylate cyclase activating peptide mRNA in a teleost retina. J Biol Rhythm 22:558–561CrossRef

Harmar AJ, Fahrenkrug J, Gozes I et al (2012) Pharmacology and functions of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide: IUPHAR review 1. Br J Pharmacol 166:4–17CrossRefPubMedPubMedCentral

Hori M, Nakamachi T, Rakwal R et al (2012a) Unraveling the ischemic brain transcriptome in a permanent middle cerebral artery occlusion mouse model by DNA microarray analysis. Dis Model Mech 5:270–283CrossRefPubMed

Hori M, Nakamachi T, Rakwal R et al (2012b) Transcriptomics and proteomics analyses of the PACAP38 influenced ischemic brain in permanent middle cerebral artery occlusion model mice. J Neuroinflamm 9:256–274CrossRef

Hori M, Nakamachi T, Shibato J et al (2014) PACAP38 differentially effects genes and CRMP2 protein expression in ischemic core and penumbra regions of permanent middle cerebral artery occlusion model mice brain. Int J Mol Sci 15:17014–17034CrossRefPubMedPubMedCentral

Izumi S, Seki T, Shioda S, Zhou CJ, Arimura A, Koide R (2000) Ultrastructural localization of PACAP immunoreactivity in the rat retina. Ann NY Acad Sci 921:317–320CrossRefPubMed

Jarkman S, Kato M, Bragadottir R (1998) Effects of adenylate cyclase-activating-polypeptide on the direct-current electroretinogram of the rabbit eye. Ophthalmic Res 30:199–206CrossRefPubMed

Jozsa R, Somogyvary-Vigh A, Reglodi D, Hollosy Arimura A (2001) Distribution and daily variations of PACAP in the chicken brain. Peptides 22:1371–1377CrossRefPubMed

Karlstetter M, Ebert S, Langmann T (2010) Microglia in the healthy and degenerating retina: insights from novel mouse models. Immunobiology 215:685–691CrossRefPubMed

Kettenmann H, Hanisch UK, Noda M, Verkhratsky A (2011) Physiology of microglia. Physiol Rev 91:461–553CrossRefPubMed

Kido N, Tanihara H, Honjo M (2000) Neuroprotective effects of brain-derived neurotrophic factor in eyes with NMDA-induced neuronal death. Brain Res 884:59–67CrossRefPubMed

Kubrusly RC, da Cunha MC, Reis RA et al (2005) Expression of functional receptors and transmitter enzymes in cultured Muller cells. Brain Res 1038:141–149CrossRefPubMed

Lakk M, Szabo B, Volgyi B, Gabriel R, Denes V (2012) Development-related splicing regulates pituitary adenylate cyclase-activating polypeptide (PACAP) receptors in the retina. Invest Opthalmol Vis Sci 53:7825–7832CrossRef

Lang B, Zhao L, Cai L et al (2010) GABAergic amacrine cells and visual function are reduced in PAC1R trangenic mice. Neuropharmacol 58:215–225CrossRef

Langmann T (2007) Microglia activation in retinal degeneration. J Leukoc Biol 81:1345–1351CrossRefPubMed

Lee WR, Grierson I (1977) Macrophage infiltration in the human retina. Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 203:293–309CrossRefPubMed

Li M, David C, Kikuta T, Somogyvari-Vigh A, Arimura A (2005) Signaling cascades involved in neuroprotection by subpicomolar pituitary adenylate cyclase-activating polypeptide 38. J Mol Neurosci 27:91–105CrossRefPubMed

Ma Y, Zhao S, Wang X et al (2015) A new recombinant PACAP-derived peptide efficiently promotes corneal wound repairing and lacrimal secretion. Invest Opthalmol Vis Sci 56:43336–44349

Markhotina N, Liu GJ, Martin DK (2007) Contractility of retinal pericytes grown on sillicone elastomer substrates is through a protein kinase A-mediated intracellular pathway in response to vasoactive peptides. IET Nanobiotechnol 1:44–51CrossRefPubMed

Martinez FO, Sica A, Mantovani A, Locati M (2008) Macrophage activation and polarization. Front Biosci 13:453–461CrossRefPubMed

Mathieu M, Ciario M, Trucco N et al (2004) Pituitary adenylate cyclase-activating polypeptide in the brain, spinal cord and sensory organs of the zebrafish, Danio rerio, during development. Brain Res Dev Brain Res 151:169–185CrossRefPubMed

Mathieu M, Girosi L, Vallarino M, Tagliafierro G (2005) PACAP in developing sensory and peripheral organs of the zebrafish, Danio rerio. Eur J Histochem 49:167–178PubMed

Mathis U, Schaeffel F (2007) Glucagon-related peptides in the mouse retina and the effects of deprivation of form vision. Graef’s Arch Clin Exp Opthalmol 245:267–275CrossRef

Matsumoto M, Nakamachi T, Watanabe J et al (2016) Pituitary adenylte cyclase-activating polypeptide (PACAP) is involved in adult mouse hippocampal neurogenesis after stroke. J Mol Neurosci 59:270–279CrossRefPubMed

Mester L, Kovacs K, Racz B et al (2011) Pituitary adenylate cyclase-activating polypeptide is protective against oxidative stress in human retinal pigment epithelial cells. J Mol Neurosci 43:35–43CrossRefPubMed

Miyata A, Arimura A, Dahl RR et al (1989) Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun 16:567–574CrossRef

Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969CrossRefPubMedPubMedCentral

Nakamachi T, Li M, Shioda S, Arimura A (2006) Signaling involved in pituitary adenylate cyclase-activating polypeptide-stimulated ADNP expression. Peptides 27:1859–1864CrossRefPubMed

Nakamachi T, Ohtaki H, Seki T et al (2016) PACAP suppressed dry eye signs by stimulating tear secretion. Nat Commun (in press)

Nakatani M, Seki T, Shinohara Y et al (2006) Pituitary adenylate cyclase-activating peptide (PACAP) stimulates production of interleukin-6 in rat Muller cells. Peptides 27:1871–1876CrossRefPubMed

Nilsson SF (2014) PACAP-27 and PACAP-38: vascular effects in the eye and some other tissues in the rabbit. Eur J Pharmacol 253:17–25CrossRef

Nilsson SF, De Neef P, Robberrecht P, Christophe L (1994) Characterization of ocular receptors for adenylate cyclase activating polypeptide (PACAP) and their coupling to adenylate cyclase. Exp Eye Res 58:459–467CrossRefPubMed

Njaine B, Martins RA, Santiago MF, Linden R, Silveira MS (2010) Pituitary adenylyl cyclase-activating polypeptide controls the proliferation of retinal progenitor cells through downregulation of cyclin D1. Eur J Neurosci 32:311–321CrossRefPubMed

Njaine B, Rocha-Martins M, Vieira-Vieira CH et al (2014) Pleiotropic functions of pituitary adenylyl cyclase-activating polypeptide on retinal ontogenesis: involovement of KLF4 in the control of progenitor cell proliferation. J Mol Neurosci 54:430–432CrossRefPubMed

Ohtaki H, Nakamachi T, Dohi K et al (2006) Pituitary adenylate cyclase-activating polypeptide (PACAP) decreases ischemic neuronal cell death in association with IL-6. Proc Natl Acad Sci USA 103:7488–7493CrossRefPubMedPubMedCentral

Olianas MC, Ennas MG, Lampis G, Onali P (1996) Presence of pituitary adenylate cyclase activating polypeptide in Y-79 human retinoblastoma cells. J Neurochem 67:1293–1300CrossRefPubMed

Olianas MC, Ingianni A, Sogos V, Onali P (1997) Expression of pituitary adenylate cyclase-activating polypeptide (PACAP) receptors and PACAP in human fetal retina. J Neurochem 69:1213–1218CrossRefPubMed

Onali P, Olianas MC (1994) PACAP is a potent and highly effective stimulation of adenylyl cyclase activity in the retinas of different mammalian species. Brain Res 641:132–134CrossRefPubMed

Racz B, Tamas A, Kiss P et al (2006) Involvement of ERK and CREB signaling pathways in the protective effect of PACAP in monosodium glutamate-induced retinal lesion. Ann NY Acad Sci 1070:507–511CrossRefPubMed

Racz B, Gasz B, Borsiczky B et al (2007) Protective effects of pituitary adenylate cyclase activating polypeptide in endothelia cells against oxidative stress-induced apoptosis. Gen Comp Endocrinol 153:115–123CrossRefPubMed

Reglodi D, Somogyvari-Vigh A, Vigh J et al (2001) Pituitary adenylate cyclase activating polypeptide is highly abundant in the nervous system of the anoxia-tolerant turtle, Pseudemys scripta elegans. Peptides 22:873–878CrossRefPubMed

Rocz B, Tamas A, Kiss P et al (2006) Involvement of ERK and CREB signaling pathways in the protective effect of PACAP in monosodium glutamate-induced retinal lesion. Ann NY Acad Sci 1070:507–511CrossRef

Schwartz M (2003) Macrophages and microglia in central nervous system injury: are they helpful or harmful? J Cereb Blood Flow Metab 223:385–394CrossRef

Seki T, Shioda S, Ogino D, Nakai Y, Arimura A, Koide R (1997) Distribution and ultrastructural localization of a receptor for pituitary adenylate cyclase activating polypeptide and its mRNA in the rat retina. Neurosci Lett 238:127–130CrossRefPubMed

Seki T, Shioda S, Nakai Y, Arimura A, Koide R (1998) Distribution and ultrastructural localization of pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor in the rat retina. Ann NY Acad Sci 865:408–411CrossRefPubMed

Seki T, Izumi S, Shioda S, Zhou CJ, Arimura A, Koide R (2000a) Gene expression for PACAP receptor mRNA in the rat retina by in situ hybridization and in situ RT-PCR. Ann NY Acad Sci 921:366–369CrossRefPubMed

Seki T, Shioda S, Izumi S, Arimura A, Koide R (2000b) Electron microscopic observation of pituitary adenylate cyclase-activating polypeptide (PACAP)-containing neurons in the rat retina. Peptides 21:109–113CrossRefPubMed

Seki M, Tanaka T, Nawa H et al (2004) Involvement of brain-derived neurotrophic factor in early retinal neuropathy of streptozotocin-induced diabetes in rats. Diabetes 53:2412–2419CrossRefPubMed

Seki T, Nakatani M, Taki C et al (2006) Neuroprotective effect of PACAP against kainic acid-induced neurotoxicity in rat retina. Ann NY Acad Sci 1070:531–534CrossRefPubMed

Seki T, Itoh H, Nakamachi T, Shioda S (2008) Suppression of rat retinal ganglion cell death by PACAP following optic nerve transection in the rat. J Mol Neurosci 36:57–60CrossRefPubMed

Seki T, Itoh H, Nakamachi T et al (2011) Suppression of rat retinal ganglion cell death by PACAP following transient ischemia induced by high intraocular pressure. J Mol Neurosci 43:30–34CrossRefPubMed

Sherwood NM, Krueckl SL, McRory JE (2000) The origin and function of the pituitary adenylate cyclase-activating polypeptide (PACAP)/glucagon superfamily. Endocr Rev 21:619–670PubMed

Shioda S, Nakamachi T (2015) PACAP as a neuroprotective factor in ischemic neuronal injuries. Peptides 72:202–207CrossRefPubMed

Shioda S, Ohtaki H, Nakamachi T et al (2006) Pleiotropic functions of PACAP in the CNS: neuroprotection and neurodevelopment. Ann NY Acad Sci 1070:550–560CrossRefPubMed

Shoge K, Mishima HK, Saitoh T et al (1999) Attenuation by PACAP of glutamate-induced neurotoxicity in cultured retinal neurons. Brain Res 839:66–73CrossRefPubMed

Silveira MS, Costa MR, Bossa M, Linden R (2002) Pituitary adenylyl cyclase-activating polypeptide prevents induced cell death in retinal tissue through activation of cyclic AMP-dependent protein kinase. J Biol Chem 277:16075–16080CrossRefPubMed

Skoglosa Y, Takei N, Lindholm D (1999) Distribution of pituitary adenylate cyclase activating polypeptide mRNA in the developing rat brain. Mol Brain Res 65:1–13CrossRefPubMed

Szabadfi K, Atlasz T, Kiss P et al (2012) Mice deficient in pituitary adenylate cyclase activating polypeptide (PACAP) are more suceptible to retinal ischemic injury in vivo. Neurotox Res 21:41–48CrossRefPubMed

Szabadfi K, Szabo A, Kiss P et al (2014) PACAP promotes neuron survival in early experimental diabetic retinopathy. Neurochem Int 64:84–91CrossRefPubMed

Szabo A, Danyadil B, Bognar E et al (2012) Effect of PACAP on MAP kinases, Akt and cytokine expressions in rat retinal hypoperfusion. Neurosci Lett 523:93–98CrossRefPubMed

Varga B, Szabadfi K, Kiss P et al (2011) PACAP improves functional outcome in excitotoxic retinal lesion: an electroretinographic study. J Mol Neurosci 43:44–50CrossRefPubMed

Vaudry D, Gonzalez BJ, Basille M, Yon L, Fournier A, Vaudry H (2000) Pituitary adenylate cyclase-activating polypeptide and its receptors: from structure to functions. Pharmacol Rev 52:269–324PubMed

Vaudry D, Falluel-Morel A, Bourgault S et al (2009) Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery. Pharmacol Rev 61:283–357CrossRefPubMed

Vrabec F (1975) Activated human retinal microglia under pathological conditions. Albrecht von Graefes Arch Klin Exp Ophthalmol 196:49–60CrossRefPubMed

Wada Y, Nakamachi T, Endo K et al (2013) PACAP attenuates NMDA-induced retinal damage in association with modulation of the microglia/macrophage status into an acquired deactivation subtype. J Mol Neurosci 51:493–502CrossRefPubMed

Walshe TE, Leach LL, D’Amore PA (2011) TGF-beta signaling is required for maintenance of retinal ganglion cell differentiation and survival. Neuroscience 189:123–131CrossRefPubMedPubMedCentral

Wang XY, Alm P, Hokanson R (1995) Distribution and effects of pituitay adenylate cyclase-activating peptide in the rabbit eye. Neuroscience 69:297–308CrossRefPubMed

Yamaji K, Yoshitomi T, Usui S (2005) Action of biologically active peptides on monkey iris sphincter and dilator muscles. Exp Eye Res 80:815–820CrossRefPubMed

Yoshitomi T, Yamaji K, Ishikawa H, Ohnishi Y (2002) Effect of pituitary adenylate cyclase-activating peptide on isolated rabbit iris sphincter and dilator muscles. Invest Ophthalmol Vis Sci 43:780–783PubMed

Zhang XY, Hayasaka S, Chi ZL, Cui HS, Hayasaka Y (2005) Effect of pituitary adenylate cyclase activating polypeptide (PACAP) on IL-6 and MCP-1 expression in human retinal pigment epithelial cell line. Curr Eye Res 30:1105–1111CrossRefPubMed

Titel: Pleiotropic and retinoprotective functions of PACAP
verfasst von: Seiji Shioda
Fumiko Takenoya
Nobuhiro Wada
Takahiro Hirabayashi
Tamotsu Seki
Tomoya Nakamachi
Publikationsdatum: 20.06.2016
Verlag: Springer Japan
Erschienen in: Anatomical Science International / Ausgabe 4/2016
Print ISSN: 1447-6959
Elektronische ISSN: 1447-073X
DOI: https://doi.org/10.1007/s12565-016-0351-0

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Pleiotropic and retinoprotective functions of PACAP

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