The Protective Role of PAC1-Receptor Agonist Maxadilan in BCCAO-Induced Retinal Degeneration

Vaczy, Alexandra and Reglodi, Dora and Somoskeoy, Tamas and Kovács, Krisztina and Lokos, Emese and Szabo, Edina and Tamas, Andrea and Atlasz, Tamas (2016) The Protective Role of PAC1-Receptor Agonist Maxadilan in BCCAO-Induced Retinal Degeneration. Journal of Molecular Neuroscience (60). pp. 186-194. ISSN 0895-8696, ESSN: 1559-1166

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A number of studies have proven that pituitary adenylate cyclase activating polypeptide (PACAP) is protective in neurodegenerative diseases. Permanent bilateral common carotid artery occlusion (BCCAO) causes severe degeneration in the rat retina. In our previous studies, protective effects were observed with PACAP1-38, PACAP1-27 and VIP, but not with their related peptides, glucagon or secretin in BCCAO. All three PACAP receptors (PAC1, VPAC1, VPAC2) appear in the retina. Molecular and immunohistochemical analysis demonstrated that the retinoprotective effects are most probably mainly mediated by the PAC1 receptor. The aim of the present study was to investigate the retinoprotective effects of a selective PAC1-receptor agonist maxadilan in BCCAO-induced retinopathy. Wistar rats were used in the experiment. After performing BCCAO, the right eye was treated with intravitreal maxadilan (0.1 μM or 1 μM), while the left eye was injected with vehicle. Sham-operated rats received the same treatment. Two weeks after the operation, retinas were processed for standard morphometric- and molecular analysis. Intravitreal injection of 0.1 μM or 1 μM maxadilan caused significant protection in the thickness of most retinal layers and the number of cells in the GCL compared to the BCCAO-operated eyes. In addition, 1 μM maxadilan application was more effective than 0.1 μM maxadilan treatment in the ONL, INL, IPL, and the entire retina (OLM-ILM). Maxadilan treatment significantly decreased cytokine expressions (CINC-1, IL-1α and L-selectin) in ischemia. In summary, our histological and molecular analysis showed that maxadilan, a selective PAC1 receptor agonist, has a protective role in BCCAO-induced retinal degeneration, further supporting the role of PAC1 receptor conveying the retinoprotective effects of PACAP.

Item Type: Article
Uncontrolled Keywords: ischemia, retinoprotection, maxadilan, PAC1 receptor
Subjects: R Medicine / orvostudomány > RE Ophthalmology / szemészet
Depositing User: Dr Tamás Atlasz
Date Deposited: 05 Oct 2016 05:35
Last Modified: 05 Oct 2016 05:35

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