Degree of damage compensation by various PACAP treatments in monosodium glutamate-induced retinal degeneration

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 mu l 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.