Neurotoxicity Research

, Volume 21, Issue 1, pp 41–48

Mice Deficient in Pituitary Adenylate Cyclase Activating Polypeptide (PACAP) are More Susceptible to Retinal Ischemic Injury In Vivo

  • K. Szabadfi
  • T. Atlasz
  • P. Kiss
  • B. Danyadi
  • A. Tamas
  • Zs. Helyes
  • H. Hashimoto
  • N. Shintani
  • A. Baba
  • G. Toth
  • R. Gabriel
  • D. Reglodi
Article

DOI: 10.1007/s12640-011-9254-y

Cite this article as:
Szabadfi, K., Atlasz, T., Kiss, P. et al. Neurotox Res (2012) 21: 41. doi:10.1007/s12640-011-9254-y

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuroprotective peptide exerting protective effects in neuronal injuries. We have provided evidence that PACAP is neuroprotective in several models of retinal degeneration in vivo. Our previous studies showed that PACAP treatment ameliorated the damaging effects of chronic hypoperfusion modeled by permanent bilateral carotid artery occlusion. We have also demonstrated in earlier studies that treatment with PACAP antagonists further aggravates retinal lesions. It has been shown that PACAP deficient mice have larger infarct size in cerebral ischemia. The aim of this study was to compare the degree of retinal damage in wild type and PACAP deficient mice in ischemic retinal insult. Mice underwent 10 min of bilateral carotid artery occlusion followed by 2-week reperfusion period. Retinas were then processed for histological analysis. It was found that PACAP deficient mice had significantly greater retinal damage, as shown by the thickness of the whole retina, the morphometric analysis of the individual retinal layers, and the cell numbers in the inner nuclear and ganglion cell layers. Exogenous PACAP administration could partially protect against retinal degeneration in PACAP deficient mice. These results clearly show that endogenous PACAP reacts as a stress-response peptide that is necessary for endogenous protection against different retinal insults.

Keywords

PACAP knockoutRetinaTransient ischemiaEndogenous PACAPIntravitreal PACAP treatment

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • K. Szabadfi
    • 1
  • T. Atlasz
    • 2
  • P. Kiss
    • 3
  • B. Danyadi
    • 3
  • A. Tamas
    • 3
  • Zs. Helyes
    • 4
  • H. Hashimoto
    • 5
    • 6
    • 7
  • N. Shintani
    • 5
  • A. Baba
    • 5
  • G. Toth
    • 8
  • R. Gabriel
    • 1
  • D. Reglodi
    • 3
  1. 1.Departments of Experimental Zoology and NeurobiologyUniversity of PecsPecsHungary
  2. 2.Department of SportbiologyUniversity of PecsPecsHungary
  3. 3.Department of Anatomy, PTE-MTA “Lendulet” PACAP Research TeamUniversity of PecsPecsHungary
  4. 4.Departments of Pharmacology and PharmacotherapyUniversity of PecsPecsHungary
  5. 5.Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical SciencesOsaka UniversityOsakaJapan
  6. 6.Center for Child Mental Development, United Graduate School of Child DevelopmentOsaka University, Kanazawa University and Hamamatsu University School of MedicineOsakaJapan
  7. 7.Department of Molecular Pharmaceutical Science, Graduate School of MedicineOsaka UniversityOsakaJapan
  8. 8.Department of Medical ChemistryUniversity of SzegedOsakaHungary