Pituitary adenylate cyclase activating polypeptide (
PACAP) is a neuroprotective
peptide exerting protective effects in neuronal
injuries. We have provided evidence that
PACAP is neuroprotective in several models of
retinal degeneration in vivo. Our previous studies showed that
PACAP treatment ameliorated the damaging effects of chronic hypoperfusion modeled by permanent bilateral carotid artery occlusion. We have also demonstrated in earlier studies that treatment with
PACAP antagonists further aggravates
retinal lesions. It has been shown that
PACAP deficient mice have larger
infarct size in
cerebral ischemia. The aim of this study was to compare the degree of
retinal damage in wild type and
PACAP deficient mice in ischemic
retinal insult. Mice underwent 10 min of bilateral carotid artery occlusion followed by 2-week reperfusion period. Retinas were then processed for histological analysis. It was found that
PACAP deficient mice had significantly greater
retinal damage, as shown by the thickness of the whole retina, the morphometric analysis of the individual
retinal layers, and the cell numbers in the inner nuclear and
ganglion cell layers. Exogenous
PACAP administration could partially protect against
retinal degeneration in
PACAP deficient mice. These results clearly show that endogenous
PACAP reacts as a stress-response
peptide that is necessary for endogenous protection against different
retinal insults.