title: PACAP Is Protective in a Rat Model of Retinopathy of Prematurity.
abstract: The oxygen-induced retinopathy (OIR) is a well-established rodent model of retinopathy of prematurity (ROP), which is one of the most common causes of childhood visual impairment affecting preterm babies. Pituitary adenylate cyclase-activating polypeptide (PACAP) is known to have neuroprotective effects. Several studies have revealed the presence of PACAP and its receptors in the retina and reported its protective effects in ischemic and diabetic retinopathy. In this study, we investigated whether PACAP administration can influence the vascular changes in the rat OIR model. OIR was generated by placing the animals in daily alternating 10/50 oxygen concentrations from postnatal day (PD) 0 to PD14 then returned them to room air. Meanwhile, animals received PACAP or saline intraperitoneally or intravitreally from PD1 to PD8 or on PD11, PD14, and PD17, respectively. On PD19 ± 1, the retinas were isolated and the vessels were visualized by isolectin staining. The percentage of avascular to whole retinal areas and the number of branching points were measured. Change in cytokine expression was also determined. Intravitreal treatment with PACAP remarkably reduced the extent of avascular area compared to the non- and saline-treated OIR groups. Intraperitoneal PACAP injection did not influence the vascular extent. Retinal images of room-air controls did not show vascular alterations. No changes in the number of vessel branching were observed after treatments. Alterations in cytokine profile after local PACAP injection further supported the protective role of the peptide. This is the first study to examine the effects of PACAP in ROP. Although the exact mechanism is still not revealed, the present results show that PACAP treatment can ameliorate the vascular changes in the animal model of ROP.
authors: Department of Anatomy, PTE-MTA "Lendulet" PACAP Research Team, University of Pecs, Pecs, Hungary.|Department of Obstetrics and Gynecology, University of Pecs, Pecs, Hungary.
authors: Timea
authors: T
authors: Kvarik
authors: Department of Anatomy, PTE-MTA "Lendulet" PACAP Research Team, University of Pecs, Pecs, Hungary.|Department of Obstetrics and Gynecology, University of Pecs, Pecs, Hungary.
authors: Barbara
authors: B
authors: Mammel
authors: Department of Anatomy, PTE-MTA "Lendulet" PACAP Research Team, University of Pecs, Pecs, Hungary.
authors: Dora
authors: D
authors: Reglodi
authors: Department of Biochemistry and Medical Chemistry, University of Pecs, Pecs, Hungary.
authors: Krisztina
authors: K
authors: Kovacs
authors: Department of Anatomy, PTE-MTA "Lendulet" PACAP Research Team, University of Pecs, Pecs, Hungary.
authors: Dora
authors: D
authors: Werling
authors: Department of Anatomy, PTE-MTA "Lendulet" PACAP Research Team, University of Pecs, Pecs, Hungary.
authors: Brigitta
authors: B
authors: Bede
authors: Department of Anatomy, PTE-MTA "Lendulet" PACAP Research Team, University of Pecs, Pecs, Hungary.
authors: Alexandra
authors: A
authors: Vaczy
authors: Department of Anatomy, PTE-MTA "Lendulet" PACAP Research Team, University of Pecs, Pecs, Hungary.
authors: Eszter
authors: E
authors: Fabian
authors: Department of Medical Chemistry, University of Szeged, Szeged, Hungary.
authors: Gabor
authors: G
authors: Toth
authors: Department of Anatomy, PTE-MTA "Lendulet" PACAP Research Team, University of Pecs, Pecs, Hungary.
authors: Peter
authors: P
authors: Kiss
authors: Department of Anatomy, PTE-MTA "Lendulet" PACAP Research Team, University of Pecs, Pecs, Hungary.
authors: Andrea
authors: A
authors: Tamas
authors: Department of Obstetrics and Gynecology, University of Pecs, Pecs, Hungary.
authors: Tibor
authors: T
authors: Ertl
authors: Department of Obstetrics and Gynecology, University of Pecs, Pecs, Hungary.
authors: Judit
authors: J
authors: Gyarmati
authors: Department of Anatomy, PTE-MTA "Lendulet" PACAP Research Team, University of Pecs, Pecs, Hungary. attam@gamma.ttk.pte.hu.|Department of Sportbiology, University of Pecs, Ifjusag utja 6, Pecs, 7624, Hungary. attam@gamma.ttk.pte.hu.|Janos Szentagothai Research Center, University of Pecs, Pecs, Hungary. attam@gamma.ttk.pte.hu.
authors: Tamas
authors: T
authors: Atlasz
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D008297:Male; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects; D012178:Retinopathy of Prematurity / Q000188:drug therapy*
chemical_list: D016207:Cytokines; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide
keywords: Muller glial cell; Neovascularization; Oxygen-induced retinopathy; Retina