Protective Role of Endogenous PACAP in Inflammation-induced Retinal Degeneration

Title:Protective Role of Endogenous PACAP in Inflammation-induced Retinal Degeneration

Volume: 24 Issue: 30

Author(s): Alexandra Vaczy, Petra Kovari, Krisztina Kovacs, Kinga Farkas, Edina Szabo, Timea Kvarik, Bela Kocsis, Balazs Fulop, Tamas Atlasz*Dora Reglodi

Affiliation:

• Department of Anatomy, MTA-PTE PACAP Research Team, University of Pecs, Medical School, Pecs,Hungary

Keywords: Retina, PACAP, knock out, LPS, inflammation, neuroprotection.

Abstract: Purpose: Pituitary adenylate Cyclase-Activating Polypeptide (PACAP) is a neuroprotective peptide that has been shown to exert protective effects in different models of neurodegenerative diseases, including retinal degenerations. Data obtained from PACAP-deficient (PACAP KO) mice provide evidence that endogenous PACAP has a neuroprotective role in different pathologies. PACAP KO mice show enhanced sensitivity to different insults, such as oxidative stress, hypoxia and inflammation. The aim of the present study was to investigate the protective effects of endogenous PACAP in retinal inflammation.

Methods: Endotoxin-induced eye inflammation was induced by intraperitoneal injection of lipopolysaccharide (LPS) in PACAP KO and wild-type (Wt) mice. After LPS treatment, retinas were processed for histological examination. To detect the alterations of different proteins and cytokines, immunohistochemical, western blot and cytokine array were used. We also performed dark-adapted electroretinography (ERG) to detect the functional differences.

Results: The thickness of nearly all layers was significantly less in LPS-injected PACAP KO mice compared to Wt animals. Increased expression of Glial Fibrillary Acidic Protein (GFAP) was induced in Müller glial cells after LPS treatment, which was more intense in PACAP KO mice. The levels of pAkt and pGSK were decreased in PACAP KO group during inflammation. LPS treatment significantly increased cytokines (sICAM-1, JE, TIMP-1) in both treated groups, but it was more expressed in PACAP KO animals. Furthermore, ERG responses were disturbed after LPS injection in PACAP KO mice.

Conclusion: Our results showed that endogenous PACAP has a protective role in LPS-caused retinal inflammation.

Cite this article as:

Vaczy Alexandra , Kovari Petra , Kovacs Krisztina , Farkas Kinga , Szabo Edina , Kvarik Timea , Kocsis Bela , Fulop Balazs , Atlasz Tamas *, Reglodi Dora , Protective Role of Endogenous PACAP in Inflammation-induced Retinal Degeneration, Current Pharmaceutical Design 2018; 24 (30) . https://dx.doi.org/10.2174/1381612824666180924141407