title: The Protective Role of PAC1-Receptor Agonist Maxadilan in BCCAO-Induced Retinal Degeneration.
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.
authors: Department of Anatomy, MTA-PTE PACAP Research Team, University of Pecs, Pecs, Hungary.
authors: A
authors: A
authors: Vaczy
authors: Department of Anatomy, MTA-PTE PACAP Research Team, University of Pecs, Pecs, Hungary.
authors: D
authors: D
authors: Reglodi
authors: Department of Anatomy, MTA-PTE PACAP Research Team, University of Pecs, Pecs, Hungary.
authors: T
authors: T
authors: Somoskeoy
authors: Department of Biochemistry and Medical Chemistry, University of Pecs, Pecs, Hungary.
authors: K
authors: K
authors: Kovacs
authors: Department of Anatomy, MTA-PTE PACAP Research Team, University of Pecs, Pecs, Hungary.
authors: E
authors: E
authors: Lokos
authors: Department of Anatomy, MTA-PTE PACAP Research Team, University of Pecs, Pecs, Hungary.
authors: E
authors: E
authors: Szabo
authors: Department of Anatomy, MTA-PTE PACAP Research Team, University of Pecs, Pecs, Hungary.
authors: A
authors: A
authors: Tamas
authors: Department of Anatomy, MTA-PTE PACAP Research Team, University of Pecs, Pecs, Hungary. attam@gamma.ttk.pte.hu.|Department of Sportbiology, University of Pecs, Ifjusag Street 6, Pecs, H-7624, Hungary. attam@gamma.ttk.pte.hu.|Janos Szentagothai Research Center, University of Pecs, Pecs, Hungary. attam@gamma.ttk.pte.hu.
authors: T
authors: T
authors: Atlasz
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D019476:Insect Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D058449:Intravitreal Injections; D007511:Ischemia / Q000150:complications; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000819:agonists*; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D012162:Retinal Degeneration / Q000188:drug therapy* / Q000209:etiology; D012171:Retinal Vessels / Q000473:pathology
chemical_list: D016207:Cytokines; D019476:Insect Proteins; D018696:Neuroprotective Agents; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; C574015:maxadilan protein, Lutzomyia longipalpis
keywords: Ischemia; Maxadilan; PAC1 receptor; Retinoprotection