Accelerated retinal aging in PACAP knock-out mice.

Andrea Kovács-Valasek, Krisztina Szabadfi, Viktória Dénes, Bálint Szalontai, Andrea Tamás, Péter Kiss, Aliz Szabó, Gyorgy Setalo, Dóra Reglődi, Robert Gábriel

Neuroscience 2017 Apr 21

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Pituitary adenylate cyclase activating polypeptide (PACAP) is a neurotrophic and neuroprotective peptide. PACAP and its receptors are widely distributed in the retina. A number of reports provided evidence that PACAP is neuroprotective in retinal degenerations. The current study compared retina cell type-specific differences in young (3-4months) and aged adults (14-16months), of wild-type (WT) mice and knock-out (KO) mice lacking endogenous PACAP production during the course of aging. Histological, immunocytochemical and Western blot examinations were performed. The staining for standard neurochemical markers (tyrosine hydroxylase for dopaminergic cells, calbindin 28 kDa for horizontal cells, protein kinase Cα for rod bipolar cells) of young adult PACAP KO retinas showed no substantial alterations compared to young adult WT retinas, except for the specific PACAP receptor (PAC1-R) staining. We could not detect PAC1-R immunoreactivity in bipolar and horizontal cells in young adult PACAP KO animals. Some other age-related changes were observed only in the PACAP KO mice only. These alterations included horizontal and rod bipolar cell dendritic sprouting into the photoreceptor layer and decreased ganglion cell number. Also, Müller glial cells showed elevated GFAP expression compared to the aging WT retinas. Furthermore, Western blot analyses revealed significant differences between the phosphorylation state of ERK1/2 and JNK in KO mice, indicating alterations in the MAPK signaling pathway. These results support the conclusion that endogenous PACAP contributes to protection against aging of the nervous system. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Citation

Andrea Kovács-Valasek, Krisztina Szabadfi, Viktória Dénes, Bálint Szalontai, Andrea Tamás, Péter Kiss, Aliz Szabó, Gyorgy Setalo, Dóra Reglődi, Robert Gábriel. Accelerated retinal aging in PACAP knock-out mice. Neuroscience. 2017 Apr 21;348:1-10