The Protective Effects of Endogenous PACAP in Oxygen-Induced Retinopathy.

Autor: Kvarik T; Department of Anatomy, MTA-PTE PACAP Research Team, Medical School, University of Pecs, Pecs, Hungary.; Department of Obstetrics and Gynecology, Medical School, University of Pecs, Pecs, Hungary., Reglodi D; Department of Anatomy, MTA-PTE PACAP Research Team, Medical School, University of Pecs, Pecs, Hungary., Werling D; Department of Anatomy, MTA-PTE PACAP Research Team, Medical School, University of Pecs, Pecs, Hungary., Vaczy A; Department of Anatomy, MTA-PTE PACAP Research Team, Medical School, University of Pecs, Pecs, Hungary., Kovari P; Department of Anatomy, MTA-PTE PACAP Research Team, Medical School, University of Pecs, Pecs, Hungary., Szabo E; Department of Anatomy, MTA-PTE PACAP Research Team, Medical School, University of Pecs, Pecs, Hungary., Kovacs K; Department of Biochemistry and Medical Chemistry, Medical School, University of Pecs, Pecs, Hungary., Hashimoto H; Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan., Ertl T; Department of Obstetrics and Gynecology, Medical School, University of Pecs, Pecs, Hungary., Gyarmati J; Department of Obstetrics and Gynecology, Medical School, University of Pecs, Pecs, Hungary., Atlasz T; Department of Anatomy, MTA-PTE PACAP Research Team, Medical School, University of Pecs, Pecs, Hungary. attam@gamma.ttk.pte.hu.; Department of Sportbiology, University of Pecs, Pecs, Hungary. attam@gamma.ttk.pte.hu.
Jazyk: angličtina
Zdroj: Journal of molecular neuroscience : MN [J Mol Neurosci] 2021 Dec; Vol. 71 (12), pp. 2546-2557. Date of Electronic Publication: 2021 Apr 24.
DOI: 10.1007/s12031-021-01846-2
Abstrakt: Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide having trophic and protective functions in neural tissues, including the retina. Previously, we have shown that intravitreal PACAP administration can maintain retinal structure in the animal model of retinopathy of prematurity (ROP). The purpose of this study is to examine the development of ROP in PACAP-deficient and wild-type mice to reveal the function of endogenous PACAP. Wild-type and PACAP-knockout (KO) mouse pups at postnatal day (PD) 7 were maintained at 75% oxygen for 5 consecutive days then returned to room air on PD12 to develop oxygen-induced retinopathy (OIR). On PD15, animals underwent electroretinography (ERG) to assess visual function. On PD16, eyes were harvested for either immunohistochemistry to determine the percentage of the central avascular retinal area or molecular analysis to assess angiogenesis proteins by array kit and anti-apoptotic protein kinase B (Akt) change by western blot. Retinas of PACAP-deficient OIR mice showed a greater central avascular area than that of the wild types. ERG revealed significantly decreased b-wave amplitude in PACAP KO compared to their controls. Several angiogenic proteins were upregulated due to OIR, and 11 different proteins markedly increased in PACAP-deficient mice, whereas western blot analysis revealed a reduction in Akt phosphorylation, suggesting an advanced cell death in the lack of PACAP. This is the first study to examine the endogenous effect of PACAP in the OIR model. Previously, we have shown the beneficial effect of exogenous local PACAP treatment in the rat OIR model. Together with the present findings, we suggest that PACAP could be a novel retinoprotective agent in ROP.
(© 2021. The Author(s).)
Databáze: MEDLINE
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