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Journal of Molecular Neuroscience

, Volume 60, Issue 2, pp 186–194 | Cite as

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

  • A. Vaczy
  • D. Reglodi
  • T. Somoskeoy
  • K. Kovacs
  • E. Lokos
  • E. Szabo
  • A. Tamas
  • T. AtlaszEmail author
Article

Abstract

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 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 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 expression (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.

Keywords

Ischemia Retinoprotection Maxadilan PAC1 receptor 

Notes

Acknowledgments

This study was supported by OTKA K104984, K119759, Bolyai Scholarship of the Hungarian Academy of Sciences, PTE AOK Research Grant, National Brain Research Program KTIA_13_NAP-A-III/5., “New National Excellence Program,” Astellas Foundation 2016, The present scientific contribution is dedicated to the 650th anniversary of the foundation of the University of Pecs, Hungary.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • A. Vaczy
    • 1
  • D. Reglodi
    • 1
  • T. Somoskeoy
    • 1
  • K. Kovacs
    • 3
  • E. Lokos
    • 1
  • E. Szabo
    • 1
  • A. Tamas
    • 1
  • T. Atlasz
    • 1
    • 2
    • 4
    Email author
  1. 1.Department of Anatomy, MTA-PTE PACAP Research TeamUniversity of PecsPecsHungary
  2. 2.Department of SportbiologyUniversity of PecsPecsHungary
  3. 3.Department of Biochemistry and Medical ChemistryUniversity of PecsPecsHungary
  4. 4.Janos Szentagothai Research CenterUniversity of PecsPecsHungary

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