Pituitary adenylate cyclase activating polypeptide (
PACAP) has been shown to be neuroprotective in
retinal ischemia and monosodium
L-glutamate (
MSG)-induced
retinal degeneration. Here we describe how different
MSG treatments (1x and 3x application) cause
retinal damage and finally lead to the destruction of the entire inner retina and how
PACAP attenuates this effect. Newborn rats from both sexes were injected subcutaneously with 2 mg/g bodyweight
MSG on postnatal days 1, 5 and 9. The left eye was left intact while we injected 5 microl
PACAP38 solution (100 pmol) into the vitreous of the right eye with a Hamilton syringe at the time of (i) the first, (ii) the first two or (iii) all three
MSG injections. Histological analysis has shown that the above described
MSG treatment caused the entire inner plexiform layer (IPL) to degenerate, and the inner nuclear (INL) and
ganglion cell layers (GCL) seemed fused. One time
PACAP38 treatment at the first
MSG application did not change the degenerative capacity of
MSG. However, if animals received
PACAP38 into the vitreous of the eye at the first 2 or all 3 times, a substantial protective effect could be observed. The IPL remained well discernible, the INL retained 2-3 cell rows and the number of cells in the GCL was substantially higher than in the
MSG-treated retinas, and was not significantly different from that observed in the control tissue. We conclude that (i) 2 or 3 times
PACAP treatment attenuates
retinal degeneration; (ii) one
PACAP treatment does not provide protection against repeated excitotoxic insults, and (iii) repeated application of
PACAP under these experimental conditions may lead to a primed state in which further neurotoxic insults are ineffective.