Pituitary adenylate cyclase activating polypeptide (PACAP) is a member of the growing
family of neurotrophic and neuroprotective factors playing important roles during
neuronal development and protection against different types of injuries, such as Parkinson's
disease, excitotoxicity, and ischemia. As shown with other neuronal tissues, we provide
evidence that PACAP is protective in the retina against toxic injury induced by monosodium
glutamate (MSG) in vivo. The need for characterization of its fragments and analogues
has recently been emphasized. The aim of the present study was to compare the effects
of the physiologically occurring fragments PACAP1-38 and 1-27 and the widely used
antagonists (PACAP6-38 and 6-27) in retinal degeneration induced by MSG in neonatal
pups. Histological analysis showed that MSG treatment caused the degeneration of the
entire inner plexiform layer and the inner nuclear and ganglion cell layers seemed
fused. The total thickness of the retina was significantly reduced. Similar and substantial
protective effects could be observed after three treatments with PACAP1-38 and 1-27,
while MSG toxicity was further aggravated by the PACAP antagonists PACAP6-38 and 6-27.
Glutamate-induced toxicity is known to play a role in several retinal pathologies.
Our results provide further evidence for the effectiveness of the endogenously present
PACAP forms in counteracting retinotoxicity and call for further studies leading to
the discovery of potent analogues that could be used in human ophthalmic diseases.