Suppression of Ganglion Cell Death by PACAP Following Optic Nerve Transection in the Rat

Seki, Tamotsu; Itoh, Hiroyuki; Nakamachi, Tomoya; Shioda, Seiji

doi:10.1007/s12031-008-9091-5

Cited by 49 publications

(32 citation statements)

References 16 publications

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“…A similar role of PACAP in the eye has also been reported, and we have previously demonstrated that PACAP prevents the retinal ganglion cell death induced by optic nerve transection in the rat (Seki et al 2008). However, the retinoprotective actions of PACAP in response to high intraocular pressure remain unclear.…”

Section: Introductionsupporting

confidence: 74%

Suppression of Rat Retinal Ganglion Cell Death by PACAP Following Transient Ischemia Induced by High Intraocular Pressure

et al. 2010

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Glaucoma is a neurodegenerative disease in which increasing intraocular pressure leads to the progressive loss of retinal ganglion cells (RGCs) and blindness. Here, we report a neuroprotective effect of pituitary adenylate cyclase-activating polypeptide (PACAP) against RGC loss induced by high intraocular pressure in the rat. Vehicle or PACAP (1 fM to 1,000 pM) solution was injected into the vitreous body once after induction of a high intraocular pressure (110 mmHg). Seven days later, the number of viable RGCs was reduced to 45% of that in the intact control. However, PACAP treatment significantly reduced this RGC death in a bimodal manner, with peaks at 10 fM and 10-100 pM. The cAMP antagonist Rp-cAMP significantly blocked the neuroprotective effect of PACAP at both high and low doses, whereas the MAP kinase inhibitor PD-98059 only prevented the effect of the low dose of PACAP. These findings suggest that PACAP has bimodal effects in the neuroprotection of RGCs against ischemia and that these effects are mediated via different signaling pathways.

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Section: Introductionsupporting

confidence: 74%

Suppression of Rat Retinal Ganglion Cell Death by PACAP Following Transient Ischemia Induced by High Intraocular Pressure

et al. 2010

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“…PACAP has been shown to have various effects in the retina and in the retinal pathways (Atlasz et al 2007(Atlasz et al , 2008(Atlasz et al , 2009Babai et al 2005Babai et al , 2006Racz et al 2006aRacz et al , b, 2007Seki et al 2006Seki et al , 2008. PACAP protected all inner retinal layers, in correlation with previous results showing the distribution of PAC1 receptor in the retina (Seki et al 2000).…”

Section: Discussionsupporting

confidence: 87%

“…In vivo, PACAP counteracts the damaging effects of kainate, hypoperfusion, optic nerve transection and UVAinduced degeneration (Atlasz et al 2007, Atlasz et al 2010aSeki et al 2006Seki et al , 2008. We have provided several lines of evidence that PACAP is protective in MSG-induced retinal lesion (Tamas et al 2004).…”

Section: Introductionmentioning

confidence: 98%

PACAP Improves Functional Outcome in Excitotoxic Retinal Lesion: An Electroretinographic Study

et al. 2010

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Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors occur throughout the nervous system, including the retina. PACAP exerts diverse actions in the eye: it influences ocular blood flow, contraction of the ciliary muscle, and has retinoprotective effects. This has been proven in different models of retinal degeneration. The in vivo protective effects of PACAP have been shown in retinal degeneration induced by kainic acid, optic nerve transection and ischemia. We have previously shown by morphological, morphometrical and immunohistochemical analyses that intravitreal PACAP administration protects against monosodium glutamate (MSG)-induced damage in neonatal rats. The question was raised whether these apparent morphological improvements by PACAP administration also lead to functional amelioration in MSG-induced retinal damage. The aim of the present study was to investigate the functional consequences of MSG treatment and the subsequent PACAP administration using electroretinographic measurements. The histological and morphometrical analyses supported the earlier findings that PACAP protected the retina in MSG-induced excitotoxicity. ERG recordings revealed a marked decrease in both the b- and a-wave values, reflecting the function of the inner retinal layers and the photoreceptors, respectively. In retinas receiving intravitreal PACAP treatment, these values were significantly increased. Thus, the functional outcome, although not parallel with the morphology, was significantly improved after PACAP treatment. The present observations are important from the clinical point of view showing, for the first time, that PACAP treatment is able to improve the functional properties of the retina in excitotoxic damage.

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“…Seki et al [ 88 ] reported that optic nerve trauma resulted approximately 55 % loss of cells in the GCL. In this model, the number of cells in the GCL in animals treated before the operation with PACAP1-38 at 10 and 100 pmol in 3 μl saline (dose-dependent) intravitreally, was signifi cantly increased compared with the control group on the 14th day after surgery [ 88 ], providing evidence that PACAP is protective in this injury model.…”

Section: Optic Nerve Injury In the Retinamentioning

confidence: 99%

Protective Effects of PACAP in the Retina

Atlasz

Vaczy

Werling

et al. 2016

Current Topics in Neurotoxicity

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a widespread neuropeptide that is well known for its general cytoprotective effects in different neuronal injuries, such as traumatic brain and spinal cord injury, models of neurodegenerative diseases, and cerebral ischemia. PACAP and its receptors also occur in the retina. In this review, we summarize the retinoprotective effects of PACAP. In vitro, PACAP is protective against glutamate, thapsigargin, anisomycin, oxidative stress, UV light, high glucose, infl ammation, and anoxia. Both the neural retina and the pigment epithelial cells can be protected by PACAP in various experimental paradigms. In vivo, the protective effects of intravitreal PACAP treatment have been shown in the following models in rats and mice: excitotoxic injury induced by glutamate, N -methyl-D -aspartate (NMDA) or kainate, ischemic injury induced by carotid artery ligation and high intraocular pressure, degeneration caused by UV-A light, optic nerve transection, and streptozotocin-induced diabetic retinopathy as well as retinopathy of prematurity. Molecular biological methods have revealed that PACAP activates anti-apoptotic, while inhibits pro-apoptotic signaling pathways, and it also stimulates an anti-infl ammatory environment in the retina. Altogether, PACAP is suggested to be a potential therapeutic retinoprotective agent in various retinal diseases.

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Suppression of Ganglion Cell Death by PACAP Following Optic Nerve Transection in the Rat

Cited by 49 publications

References 16 publications

Suppression of Rat Retinal Ganglion Cell Death by PACAP Following Transient Ischemia Induced by High Intraocular Pressure

Suppression of Rat Retinal Ganglion Cell Death by PACAP Following Transient Ischemia Induced by High Intraocular Pressure

PACAP Improves Functional Outcome in Excitotoxic Retinal Lesion: An Electroretinographic Study

Protective Effects of PACAP in the Retina

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