The Protective Effects of Endogenous PACAP in Oxygen-Induced Retinopathy.
Knock out
Neuroprotection
PACAP
ROP
Retina
Journal
Journal of molecular neuroscience : MN
ISSN: 1559-1166
Titre abrégé: J Mol Neurosci
Pays: United States
ID NLM: 9002991
Informations de publication
Date de publication:
Dec 2021
Dec 2021
Historique:
received:
06
02
2021
accepted:
13
04
2021
pubmed:
26
4
2021
medline:
3
3
2022
entrez:
25
4
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33895966
doi: 10.1007/s12031-021-01846-2
pii: 10.1007/s12031-021-01846-2
pmc: PMC8602170
doi:
Substances chimiques
Adcyap1 protein, mouse
0
Pituitary Adenylate Cyclase-Activating Polypeptide
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Oxygen
S88TT14065
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2546-2557Informations de copyright
© 2021. The Author(s).
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