PACAP Improves Functional Outcome in Excitotoxic Retinal Lesion: An Electroretinographic Study

Abstract

Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptors occur throughout the nervous system, including the retina. PACAP exerts diverse actions in the eye: it influences ocular blood flow, contraction of the ciliary muscle, and has retinoprotective effects. This has been proven in different models of retinal degeneration. The in vivo protective effects of PACAP have been shown in retinal degeneration induced by kainic acid, optic nerve transection and ischemia. We have previously shown by morphological, morphometrical and immunohistochemical analyses that intravitreal PACAP administration protects against monosodium glutamate (MSG)-induced damage in neonatal rats. The question was raised whether these apparent morphological improvements by PACAP administration also lead to functional amelioration in MSG-induced retinal damage. The aim of the present study was to investigate the functional consequences of MSG treatment and the subsequent PACAP administration using electroretinographic measurements. The histological and morphometrical analyses supported the earlier findings that PACAP protected the retina in MSG-induced excitotoxicity. ERG recordings revealed a marked decrease in both the b- and a-wave values, reflecting the function of the inner retinal layers and the photoreceptors, respectively. In retinas receiving intravitreal PACAP treatment, these values were significantly increased. Thus, the functional outcome, although not parallel with the morphology, was significantly improved after PACAP treatment. The present observations are important from the clinical point of view showing, for the first time, that PACAP treatment is able to improve the functional properties of the retina in excitotoxic damage.