Evaluation of the protective effects of PACAP with cell-specific markers in ischemia-induced retinal degeneration
Evaluation of the protective effects of PACAP with cell-specific markers in ischemia-induced retinal degeneration
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DOI：
10.1016/j.brainresbull.2009.09.004
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发表时间：
2010-03-16
影响因子：
3.8
通讯作者：
Gabriel, Robert
中科院分区：
文献类型：
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作者：
Atlasz, Tamas;Szabadfi, Krisztina;Gabriel, Robert
腺苷酸环化酶激活多肽（PACAP）是一种神经营养和神经保护肽，在创伤性脑损伤、神经退行性疾病模型和脑缺血等多种神经元损伤中发挥保护作用。我们提供的证据表明，PACAP是在体内视网膜变性的几种模型的神经保护。在我们以前的研究中，我们发现PACAP治疗显著改善了永久性双侧颈总动脉闭塞（BCCAO）的损伤效应。在本研究中，在相同的模型中使用细胞类型特异性标记物，以进一步说明PACAP的保护作用。在大鼠中，BCCAO导致所有视网膜层的严重变性，在BCCAO后立即单侧给予PACAP（100 pmol）至一只眼睛的玻璃体中，可使其减弱。3周后对视网膜进行免疫组织化学处理。对囊泡谷氨酸转运蛋白1（VGLUT 1）、囊泡γ-氨基丁酸转运蛋白（VGAT）、蛋白激酶C α（PKC α）、胶质细胞酸性蛋白（GFAP）和钙结合蛋白（如钙结合蛋白、钙视网膜蛋白、小清蛋白）进行免疫标记。在BCCAO视网膜，强度的免疫阳性的所有抗血清显着下降，除了在GFAP的情况下。在PACAP处理的视网膜中，免疫染色与对照动物相似。总之，我们的研究提出了慢性视网膜灌注不足敏感的细胞类型的免疫组化鉴定和PACAP的保护作用。该分析表明，PACAP的视网膜保护作用不是表型特异性的，而是影响一般的细胞保护途径，而不管慢性低灌注视网膜中的神经元亚型。(C)2009 Elsevier Inc. All rights reserved.
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and neuroprotective peptide that has been shown to exert protective effects in different neuronal injuries, such as traumatic brain injury, models of neurodegenerative diseases and cerebral ischemia. We have provided evidence that PACAP is neuroprotective in several models of retinal degeneration in vivo. In our previous studies we showed that PACAP treatment significantly ameliorated the damaging effects of permanent bilateral common carotid artery occlusion (BCCAO). In the present study cell-type-specific markers were used in the same models in order to further specify the protective effects of PACAP. In rats BCCAO led to severe degeneration of all retinal layers that was attenuated by PACAP (100 pmol) administered unilaterally immediately following BCCAO into the vitreous body of one eye. Retinas were processed for immunohistochemistry after 3 weeks. Immunolabeling was executed for vesicular glutamate transporter 1 (VGLUT 1), vesicular gamma-aminobutyric acid transporter (VGAT), protein kinase C alpha (PKC alpha), glial fibrillary acidic protein (GFAP) and calcium-binding proteins, such as calbindin, calretinin, parvalbumin. In BCCAO retinas, intensity of immunopositivity for all antisera was dramatically decreased, except in the case of GFAP. In PACAP-treated retinas, immunostaining was similar to that of the control animals. In summary, our study presented immunohistochemical identification of cell types sensitive to chronic retinal hypoperfusion and the protective effects of PACAP. This analysis revealed that the retinoprotective effects of PACAP are not phenotype-specific, but it rather influences general cytoprotective pathways irrespective of the neuronal subtypes in the retina subjected to chronic hypoperfusion. (C) 2009 Elsevier Inc. All rights reserved.