Article

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. SzabadfiAffiliated withDepartments of Experimental Zoology and Neurobiology, University of Pecs
  • , T. AtlaszAffiliated withDepartment of Sportbiology, University of Pecs
  • , P. KissAffiliated withDepartment of Anatomy, PTE-MTA “Lendulet” PACAP Research Team, University of Pecs
  • , B. DanyadiAffiliated withDepartment of Anatomy, PTE-MTA “Lendulet” PACAP Research Team, University of Pecs
  • , A. TamasAffiliated withDepartment of Anatomy, PTE-MTA “Lendulet” PACAP Research Team, University of Pecs
  • , Zs. HelyesAffiliated withDepartments of Pharmacology and Pharmacotherapy, University of Pecs
  • , H. HashimotoAffiliated withLaboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka UniversityCenter for Child Mental Development, United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University School of MedicineDepartment of Molecular Pharmaceutical Science, Graduate School of Medicine, Osaka University
  • , N. ShintaniAffiliated withLaboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University
  • , A. BabaAffiliated withLaboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University
    • , G. TothAffiliated withDepartment of Medical Chemistry, University of Szeged
    • , R. GabrielAffiliated withDepartments of Experimental Zoology and Neurobiology, University of Pecs
    • , D. ReglodiAffiliated withDepartment of Anatomy, PTE-MTA “Lendulet” PACAP Research Team, University of Pecs Email author 

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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 knockout Retina Transient ischemia Endogenous PACAP Intravitreal PACAP treatment