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 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-caused
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 Muller 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.
