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A procedure for recording the electroretinogram (ERG) in pigmented mice, C57BL, based on the ERG recording technique reported previously in albino mice, ICR, and giving careful consideration to the influence of anesthetics and dark-adaptation, was developed in order to examine retinal toxicity. Pigmented mice were given a single i.v. injection of monoiodoacetic acid (IAA), a known retinotoxic compound, via a tail vein at a dose of 30, 45 or 60 mg/kg, and the ERG was recorded periodically over the next 14 days. In addition, the retinas were examined histopathologically on day 15. The results were as follows. 1. The oscillatory potentials were not distinct in the ERGs from mice anesthetized with pentobarbital as compared to the ERGs from non-anesthetized mice. ERG waveforms obtained from mice anesthetized with a mixture of urethane, xylazine and ketamine or xylazine and ketamine were almost the same as those obtained from non-anesthetized mice. Therefore, the ERGs were recorded under mixed anesthesia, ketamine and xylazine, in the following study. Stable ERGs could be recorded after 40 min of dark-adaptation. 2. IAA at doses of 30 and 45 mg/kg caused slight depression of the amplitudes of the a-, b- and c-waves; however, these changes were no longer observed 7 days after dosing. At a dose of 60 mg/kg, the ERG waves were markedly depressed 1 day after dosing, and recovery was not observed until day 14. 3. Upon histopathologic examination of the retinas, a remarkable decrease in visual cells and thinning of the rod and cone layers and outer plexiform layer were observed with IAA at a dose of 60 mg/kg. 4. Using this newly developed recording technique, it was confirmed that stable ERGs could be recorded from pigmented mice repeatedly for 14 days, and the effects of IAA on the ERG could be detected. Histopathological abnormalities in the retinas correlated well with the changes in the ERGs. These results indicate that the newly developed ERG recording procedure is useful for evaluating retinal toxicity in pigmented mice.

Effects of intravitreal injection of levofloxacin (LVFX) on the electroretinogram (ERG), visual evoked potential (VEP), and retinal histology were studied in 23 albino and 23 pigmented rabbits to establish the non-toxic intravitreal dosage of LVFX. Doses of 200, 500, 1,000 or 2,000 micrograms of LVFX were injected intravitreally. The ERG and VEP were recorded before injection, and 3 hours, 2 days, 1 week, 2 weeks and 4 weeks after injection. The oscillatory potential transiently deteriorated with 1,000 and 2,000 micrograms doses of LVFX in albino and pigmented rabbits. No ERG changes were observed with 200 and 500 micrograms doses. No abnormal changes were observed in the VEP or retinal histology with any doses of LVFX. These results indicate that intravitreal injections of 200 and 500 micrograms of LVFX are nontoxic to the rabbit retina.

Effects of an intravitreal injection of melphalan on the electroretinogram and on the retinal structure were studied in albino rabbits to establish the non-toxic dose for its intravitreal use. The a-wave, the b-wave, the c-wave, the oscillatory potential and the retinal structure remained unchanged after 10-micrograms injection, but moderately changed after 20-micrograms injection and greatly deteriorated after 90-micrograms injection. A 10-micrograms injection is equal to an intravitreal concentration of about 5.9 micrograms/ml, if evenly diffused in the rabbit vitreous. Considering that colony formation of in vitro retinoblastoma cells is completely suppressed by melphalan at 4 micrograms/ml concentration, an intravitreal application of melphalan could be used as a non-surgical treatment for retinoblastoma.

The effects of antioxidant drugs on retinal ischemia-reperfusion damage were studied by electroretinograms (ERGs) from reperfused Dutch rabbit eyes. After inducing retinal ischemia by increasing the intraocular pressure (IOP) up to 140 mmHg for 60 minutes, the reperfusion was started by lowering the IOP to the normal level. Mannitol, polyethylene glycol superoxide dismutase (PEG-SOD), or ascorbic acid was administered by drip-infusion to the rabbits immediately after (early group) or 1 hr after (delayed group) the start of reperfusion. Saline, as a control, was administered by the same method as the early group. The a- and b-waves were recorded before the ischemia and during the reperfusion. In the early group treated by each drug, the recovery rates of the b-wave amplitudes at 4 hrs after the start of reperfusion were significantly greater than those in the controls. In the delayed group, the ERG recovery rate in rabbits treated with PEG-SOD was significantly better than in the controls. These results indicated that all these drugs were effective in protecting from the retina from the ischemia-reperfusion damage, and that some antioxidant drugs might be effective even when they were administered after the start of reperfusion.

The effect of melphalan (an alkylic anti-cancer drug) on rabbit and human in vitro ERGs was studied to establish the non-toxic concentration of melphalan in chemo-thermotherapy for retinoblastoma. The ERGs were recorded before and 15 min after the perfusate was changed from the control solution to a melphalan-containing solution. Melphalan 10 micrograms/ml and 40 micrograms/ml caused no significant effect on the a-wave, the b-wave, or the oscillatory potential in either the rabbit or the human in vitro ERG. Melphalan 50 micrograms/ml significantly reduced the b-wave, but the change was reversible. Considering the minimum inhibitory concentration of melphalan against retinoblastoma cells on colony assay (4 micrograms/ml), melphalan is one of the most effective drugs for the conservative treatment of retinoblastoma.

The effects of lomefloxacin on the in-vitro ERG were studied in the rabbit. The ERG was unchanged during perfusion with 100 microM lomefloxacin. The oscillatory potential was selectively diminished with 300 microM lomefloxacin. The suppressive effect of 300 microM lomefloxacin on the oscillatory potential was antagonized by 0.2 microM bicuculline or 0.2 microM picrotoxin. Bicuculline (0.2 microM) or picrotoxin (0.2 microM) antagonized the suppressive effect of GABA (50 microM) on the oscillatory potential. Bicuculline (1.0 microM) alone, picrotoxin (1.0 microM) alone or GABA (50 microM) alone did not augment the oscillatory potential. The findings of the present study suggested that lomefloxacin, a new quinolone agent, inhibits GABA receptor binding in the rabbit retina.

Endothelin, a novel, potent, and long-acting vasoconstrictor peptide, is thought to regulate retinal circulation and its autoregulation. A disturbance in the regulation of endothelin production might contribute to the pathogenesis of retinochoroidal or optic nerve diseases. We examined the effects of endothelin on the retina and the optic nerve using the electroretinogram (ERG) and visual evoked potential (VEP). Six male albino rabbits underwent intravitreal injection of 0.1 ml (10(-5) mol/l) endothelin-1 in the right eye. Six other male albino rabbits, which were injected intravitreally with 0.1 ml of Opeguard-MA in the right eye, were used as controls. Endothelin-1 caused marked constriction of retinal vessels and pallor of the optic nerve head. These findings persisted for 10 days after endothelin-1 injection. The amplitude of the b-wave and the latency of the oscillatory potential in the ERG were not significantly different from those in controls. On the other hand, prolongation of the VEP-N1 latency was observed for 14 days after the injection. These results indicate that endothelin acts on the circulation of the optic nerve head rather than that of the retina, and that effects persist for a relatively long period.

Effects of carteolol on ERG b-wave amplitude were investigated in dark adapted isolated perfused cat eyes. Carteolol enhanced ERG b-waves with both strong stimuli that reflect the function of both the rod and cone systems, and weak stimuli that reflect the function of the rod system. These observations suggest the following two ideas i.e.: 1. Carteolol increases the flow in retinal vessels of perfusate. or 2. Carteolol has interaction with retinal beta-adrenergic receptors related to the origin of the ERG b-wave. It is likely that both participate in the intrinsic sympathomimetic activity and the release activity of the endothelium derived relaxing factor of carteolol.

It has been shown that gamma-aminobutyric acid (GABA) is densely packed in the inner nuclear and plexiform layers in the rat retina, where it is mainly located within a subgroup of amacrine cells. This study examined the effects on the electroretinogram of GABA antagonists infused into the vitreous cavity of urethan-anesthetized rats. Infusions of the GABAA antagonist, bicuculline (0.1-10 mM, 3 microliters) significantly enhanced the b-wave amplitude and reduced the oscillatory potentials (OPs). Similar effects were also produced by infusions of the GABAB antagonist, phaclofen (10 mM, 3 microliters), although lower doses (0.1-1 mM, 3 microliters) had no effect. These results suggest that the actions of GABA, presumably released from amacrine cells, on both GABAA and GABAB receptors are involved in the normal generation of the b-wave and OPs.

Changes in electroretinograms (ERG) due to administration of chlorpyrifos were examined in rats. Male Wistar rats were intraperitoneally injected with chlorpyrifos (0.2 mmol/kg body weight), and their cholinesterase (ChE) activities and ERG were measured at various times after the injection. Amplitudes of A and B waves in ERG were more than 50% decreased and latencies of the waves were prolonged 10-20% from 5 h to 2 d after the injection. At the same time, activities of ChE in plasma, erythrocytes, brain and retinochoroid were remarkably decreased. However, the amplitudes and latencies recovered to the control level more rapidly than the ChE activities of the erythrocytes, brain and retinochoroid. Injection into rats of 0, 0.002, 0.01, 0.05 or 0.25 mmol/kg of chlorpyrifos showed that the chlorpyrifos-induced changes of ERG were dose-dependent, and that a level of 0.05 mmol/kg caused a 50% decrease in the A or B wave 5 h after the injection. These results indicate that chlorpyrifos caused abnormal ERG characterized by decreased amplitudes and prolonged latencies of A and B waves and that the abnormal ERG did not always correspond to the decreased retinochoroid or brain ChE activities.

We have investigated a method of intraoperative monitoring of anesthetic depth using the electroretinogram (ERG). The effects of enflurane on ERG were studied in 12 patients undergoing surgical procedures. Recordings were made at 0%, 0.8%, 1.7% end-tidal enflurane concentrations. There were statistically significant increases in the latencies of the a-waves, b-waves and oscillatory potentials (OP) with increasing concentrations of enflurane. The amplitudes of the a-waves were reduced with increasing concentrations of enflurane, but the amplitudes of the b-waves did not change. The latencies of OP were thought to be the most sensitive indicator of the anesthetic depth among these parameters. To apply this technique to clinical practice, there were many problems to be solved. However, this may be one of useful monitors of anesthetic depth in future.