Effects of Pituitary Adenylate-Cyclase-Activating Polypeptide on the Direct-Current Electroretinogram of the Rabbit Eye

Abstract

Pituitary adenylate-cyclase-activating polypeptide (PACAP) is a recently discovered neuropeptide present in two different forms, PACAP-27 and PACAP-38. Both peptides stimulate the catalytic enzyme adenylate cyclase in pituitary cells. This enzyme is important also regarding the function of the retinal pigment epithelium (RPE). The purpose of the study was to investigate possible influences of PACAP on the rabbit retina and the RPE as reflected in the direct-current (d.c.) electroretinogram (ERG) and the standing potential of the eye (SP). After unilateral sector vitrectomy, a continuous intraocular perfusion with a reference solution alternated with a test solution was established. The corneal d.c. ERG and the SP were recorded from both eyes with the contralateral eye as a control. Both PACAP-27 (0.1 and 1 µM) and PACAP-38 (1 µM) increased the c-wave amplitude significantly (p = 0.028, p = 0.013 and p = 0.024, respectively, n = 4) while neither PACAP-27 (0.1 and 1 µM, p > 0.05, n = 4) nor PACAP-38 (1 µM, p > 0.05, n = 4) produced any significant effects on the a- and b-wave amplitudes of the d.c. ERG. The SP response to the two substances differed with a significant elevation of the SP level with PACAP-27 (1 µM, p = 0.017, n = 4), while PACAP-38 induced a small, nonsignificant SP elevation (1 µM, p > 0.05, n = 4). Retinal penetrations during PACAP-27 (10 µM) perfusion showed an increase in transepithelial potential (TEP) c-wave (p = 0.003) as well as in slow PIII (p = 0.011, n = 3) amplitude level. The results support the presence of PACAP receptors both on the RPE and in the neural retina.

Pituitary adenylate cyclase activating polypeptide in the retina: focus on the retinoprotective effects

“…Other studies indicate that endogenous PACAP is important in maintaining the antiapoptotic mechanisms 35,36 . Functioning PACAP receptors in both the neural retina and pigment epithelial cells have been confirmed by electroretinogram examinations, showing that intraocularly infused PACAP27 and –38 induced changes in the electrical waves reflecting the activity of both the pigment layer and the neural retina 37 …”

“…35,36 Functioning PACAP receptors in both the neural retina and pigment epithelial cells have been confirmed by electroretinogram examinations, showing that intraocularly infused PACAP27 and -38 induced changes in the electrical waves reflecting the activity of both the pigment layer and the neural retina. 37 In retinal pigment epithelial cells, PACAP inhibits the interleukin-1(IL-1)-induced IL-6, -8, and monocyte chemotactic protein-1 expression. 27 Muller glial cells are one of the target cells for PACAP.…”

Modification of native collagen with cell‐adhesive peptide to promote RPE cell attachment on Bruch's membrane

“…More importantly, this simple approach may be expanded to further increase the viability of the cells. We are in the process of studying the impact of anchoring other bioactive peptides with known neurotrophic effects such as VIP and PACAP (Jarkman et al, 1998;Kishi et al, 1996) in addition to the RGDS-CBP peptide. …”

Pleiotropic and retinoprotective functions of PACAP

“…Other studies have revealed that endogenous PACAP is important in maintaining anti-apoptotic mechanisms (Racz et al 2006(Racz et al , 2007. Functioning PACAP receptors in both the neural retina and pigment epithelial cells have been confirmed by electroretinography, with changes in the electrical wave reflecting the activity of both the pigment layer and the neural retina (Jarkman et al 1998). …”