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
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.