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PACAP 可改善兴奋性视网膜病变的功能预后:一项视网膜电图研究。

PACAP improves functional outcome in excitotoxic retinal lesion: an electroretinographic study.

机构信息

Department of Pharmacology, University of Debrecen, Debrecen, Hungary.

出版信息

J Mol Neurosci. 2011 Jan;43(1):44-50. doi: 10.1007/s12031-010-9406-1. Epub 2010 Jun 22.

DOI:10.1007/s12031-010-9406-1
PMID:20567936
Abstract

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.

摘要

垂体腺苷酸环化酶激活肽 (PACAP) 及其受体存在于整个神经系统中,包括视网膜。PACAP 在眼睛中发挥多种作用:它影响眼血流、睫状肌收缩,并具有视网膜保护作用。这已在不同的视网膜变性模型中得到证实。在红藻氨酸、视神经横断和缺血诱导的视网膜变性中,体内 PACAP 的保护作用已得到证明。我们之前通过形态学、形态计量学和免疫组织化学分析表明,玻璃体内给予 PACAP 可预防新生大鼠中谷氨酸单钠 (MSG) 诱导的损伤。问题是 PACAP 给药引起的这些明显的形态改善是否也导致 MSG 诱导的视网膜损伤的功能改善。本研究的目的是使用视网膜电图测量来研究 MSG 处理后的功能后果和随后的 PACAP 给药。组织学和形态计量学分析支持了先前的发现,即 PACAP 可保护 MSG 诱导的兴奋性毒性中的视网膜。ERG 记录显示 b-和 a-波值明显降低,分别反映了内视网膜层和光感受器的功能。在接受玻璃体内 PACAP 治疗的视网膜中,这些值显着增加。因此,尽管与形态学不平行,但 PACAP 治疗后的功能结果显着改善。从临床角度来看,这些观察结果很重要,首次表明 PACAP 治疗能够改善兴奋性损伤中视网膜的功能特性。

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本文引用的文献

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Ann N Y Acad Sci. 2010 Jul;1200:128-39. doi: 10.1111/j.1749-6632.2010.05512.x.
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Electrophysiological evidence of early functional damage in glaucoma and ocular hypertension.青光眼和高眼压症早期功能损伤的电生理学证据。
Invest Ophthalmol Vis Sci. 2010 Feb;51(2):1216-22. doi: 10.1167/iovs.09-3409. Epub 2009 Oct 22.
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Evaluation of the protective effects of PACAP with cell-specific markers in ischemia-induced retinal degeneration.
BGP-15,一种羟肟酸衍生物,对 2 型糖尿病大鼠模型的视网膜保护作用优于格列本脲、二甲双胍和吡格列酮。
Int J Mol Sci. 2020 Mar 19;21(6):2124. doi: 10.3390/ijms21062124.
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Spatiotemporal Expression Changes of PACAP and Its Receptors in Retinal Ganglion Cells After Optic Nerve Crush.视神经挤压后 PACAP 及其受体在视网膜神经节细胞中的时空表达变化。
J Mol Neurosci. 2019 Jul;68(3):465-474. doi: 10.1007/s12031-018-1203-2. Epub 2018 Nov 10.
5
New GABA modulators protect photoreceptor cells from light-induced degeneration in mouse models.新型 GABA 调节剂可保护光诱导模型小鼠中的光感受器细胞免于变性。
FASEB J. 2018 Jun;32(6):3289-3300. doi: 10.1096/fj.201701250R. Epub 2018 Jan 24.
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Protective Effect of Prunus Cerasus (Sour Cherry) Seed Extract on the Recovery of Ischemia/Reperfusion-Induced Retinal Damage in Zucker Diabetic Fatty Rat.樱桃李籽油对 Zucker 糖尿病肥胖大鼠缺血再灌注诱导的视网膜损伤恢复的保护作用。
Molecules. 2017 Oct 21;22(10):1782. doi: 10.3390/molecules22101782.
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PACAP Is Protective in a Rat Model of Retinopathy of Prematurity.垂体腺苷酸环化酶激活肽对早产儿视网膜病变大鼠模型具有保护作用。
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PLoS One. 2014 Jan 6;9(1):e84800. doi: 10.1371/journal.pone.0084800. eCollection 2014.
评估 PACAP 及其细胞特异性标记物在缺血性诱导的视网膜变性中的保护作用。
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Non-mitogenic human acidic fibroblast growth factor reduces retinal degeneration induced by sodium iodate.无促有丝分裂作用的人酸性成纤维细胞生长因子可减轻碘酸钠诱导的视网膜变性。
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Ann N Y Acad Sci. 2009 Apr;1163:348-52. doi: 10.1111/j.1749-6632.2008.03650.x.
6
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