A marked effect of prostaglandins on the b- and c-waves of the direct current electroretinogram was recently reported by our laboratory. The increased b- and c-wave amplitudes in response to prostaglandins may be mediated by cyclic nucleotides acting on fluid and ion transport across the retinal pigment epithelium (RPE). Forskolin is known to increase cyclic adenosine monophosphate in a number of tissues, among them the RPE. To study possible effects of forskolin on the ERG vitrectomy was performed on rabbit eyes, followed by intraocular irrigation with a forskolin solution (10 micrograms/ml PHS). Forskolin produced reversible ERG changes with increase in a- (24%, p less than 0.001), b- (25%, p less than 0.001) and c-wave (53%, p less than 0.001) amplitudes and elevation (about 1.0-1.5 mV, p less than 0.01) of the standing potential of the eye. The increase in c-wave amplitude was significantly greater than that of the a- (p less than 0.05) and b- (p less than 0.01) wave amplitudes, which seems to imply a primary or at least major effect on the RPE.

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.

Albino rabbits were exposed to strong visible light that had passed several infrared-absorbing filters. Photic damage to the retina and pigment epithelium was studied by means of the direct current electroretinogram (dc-ERG) which allows stable registrations of the slow c-wave from the pigment epithelium as well as the relatively fast a- and b-waves from the neuroretina. The exposure to light for 4 h gave rise to striking changes in the ERG: there was only a 25% decrease in the b-wave but a total disappearance of the normally very large c-wave. At the site of the c-wave in the ERG there appeared a negative trough. The electroretinographic evidence of this study seems to indicate a profound injury to the pigment epithelium (pigment epithelial cells and/or tight junctions) after exposure to strong visible light.

This study was undertaken to investigate further the responsiveness of the albino rabbit retinal pigment epithelium and the inner retina to adrenergic agents as reflected in changes of the direct-current electroretinogram and of the standing potential of the eye. After unilateral vitrectomy on albino rabbits, a continuous intraocular perfusion with a reference solution was established. The reference solution was then alternated with the test solution. The direct-current electroretinogram and the standing potential were recorded from both eyes with a scleral contact lens and a reference electrode connected to matched calomel half-cells. An in vivo experimental technique that allows intraocular perfusion of a test substance and simultaneous intraretinal microelectrode measurements was also used. The alpha-adrenergic agonist phenylephrine (0.04 microM, n = 8) produced a reversible increase in c-wave amplitude (48%, p < 0.001) and also a small increase in b-wave amplitude (12%, p < 0.002). There was no significant influence on the a-wave amplitude. The standing potential was elevated at 1694 +/- 362 microV (mean +/- SEM) (p < 0.002). The alpha 2-adrenergic agonist clonidine caused similar effects on the electroretinogram, although at a higher concentration (40 microM, n = 5), with an elevation of the c-wave (25%, p < 0.001) and a small b-wave increase (12% p < 0.002). No significant influence on the a-wave or on the standing potential was found. Intraretinal direct-current electroretinogram-recordings during intraocular perfusion with phenylephrine showed an increase in transepithelial potential (p < 0.004; n = 6), accompanied by a reduction of the slow PIII (p < 0.0035; n = 6). The c-wave increase resulting from alpha-adrenergic stimulation seems to be generated partly across the retinal pigment epithelium, with an increase in transepithelial potential, combined with a reduction of the slow PIII. The elevation of the b-wave amplitude, together with the influence on the slow PIII, suggests alpha-adrenergic effects also on the inner retina. The experimental technique used in this study with intraocular perfusion after vitrectomy and simultaneous intraretinal direct-current recordings seems to be a practicable method for studies of the influence of pharmacologic agents on the retina and the retinal pigment epithelium.

A few microliters of a prostaglandin preparation (PGE2 or PGF2 alpha) were injected via the ora serrata into the posterior vitreous of one of the eyes in albino rabbits. The fellow eye received an equal volume of saline intravitreally and served as control. The DC electroretinogram (ERG) and the standing potential of the eye (SP) were recorded directly with corneal contact lenses, very stable calomel electrodes, and under very constant anesthesia. The b- and c-wave amplitudes increased in response to 0.1 and 1.0 microgram of PGE2 and PGF2 alpha, respectively. At medium doses there was an increase in the b- and c-wave amplitudes followed by a long-lasting reduction. At very high, nonphysiological doses of PGE2, b- and c-wave amplitudes decreased as compared with the control eye. Prostaglandins modify inflammatory reactions, influence ion transport across membranes, modulate synaptic transmission, and regulate blood flow to various organs. Effects of extremely low doses on the retina and pigment epithelium might indicate a transmitter-like nature of prostaglandins. The present experimental model might be of use in studies of inflammatory eye disease, prostaglandin inhibitors, and characteristics of the pigment epithelial membranes.