The effect of iodoacetic acid on the electroretinogram and oscillatory potentials in rabbits

It has been shown that a single injection of iodoacetic acid selectively (but temporarily) abolishes the b-wave of the electroretinogram. We examined whether such use of this chemical further substantiate our claim that the b-wave of the electroretinogram is a composite potential resulting from the summation (or integration) of faster retinal potentials, usually referred to as the oscillatory potentials. Full-field electroretinograms were recorded from adult New Zealand rabbits before and after a single, bolus injection of 15mg/kg of buffered iodoacetic acid. Both the 1–1000 Hz electroretinogram and the 100–1000 Hz oscillatory potentials were recorded simultaneously. The oscillatory potentials considered in this study were those normally seen on the rising phase of the b-wave. Following the intravenous injection of iodoacetic acid, there was a progressive decrease in the amplitude and peak time of the b-wave. This observation also was reflected in the oscillatory potential recordings, in which the long-latency oscillatory potentials (3 and 4) progressively disappeared while oscillatory potential 2 remained. We believe that these findings further support our contention that the oscillatory potentials are major components of the b-wave.     

Maturation of the electroretinogram of the neonatal rabbit

The development of the electroretinogram in the rabbit has been said to proceed with first the a-wave, then the b-wave and last the oscillatory potentials. The aim of our study was to reexamine this claim with special attention to the oscillatory potentials. Albino rabbits from the same litter were studied at weekly intervals for five weeks from the first week of life. A Grass photostimulator was used in light and dark adaptation and 50 amplified responses were averaged. Both 1–1000 Hz (electroretinogram) and 100–1000 Hz (oscillatory potential) band-widths were recorded simultaneously. The a-wave was the earliest signal to appear, at the second week of life. A rapid growth of the b-wave and oscillatory potentials was then noted between the second and third weeks, followed by a slower change. They evolved at the same rate, each with an increase in amplitude and decrease in peak time. The change in form of the b-wave was consistent with the sequential formation of each potential as the rabbit matured. The finding of simultaneous development of the b-wave and oscillatory potentials in the aging neonatal rabbit is contrary to previous reports.     

Nontoxic concentration of kanamycin and gentamicin for intravitreal use — evaluated by in vitro ERG

The effects of kanamycin (KM) and gentamicin (GM) on the in-vitro electroretinogram of the albino rabbit were studied. The b-wave and oscillatory potentials (OPs) were unchanged by 0.1 mM KM. The photopic b-wave and OPs were slightly suppressed by 0.4 mM. The b-wave and OPs were not deteriorated by 23 µg/ml (approximately 0.05 mM) GM. The photopic b-wave and OPs were slightly suppressed by 46 µg/ml (approximately 0.1 mM) GM. The minimum concentration affecting the ERG was tentatively defined as the mean of the minimum concentration needed to change the ERG and the maximum concentration which induced no discernible changes in the ERG. The minimum concentration of KM and GM affecting the ERG were 0.25mM (approximately 150 g/ml) and 35 g/ml (approximately 0.075 mM) respectively. The minimum concentration of KM affecting the ERG was higher than its minimum inhibitory concentration against Staphylococcus aureus and Streptococcus pneumoniae. The minimum concentration of GM affecting the ERG was higher than its mimimum inhibitory concentration against Staphylococcus aureus, Streptococcus pneumoniae and Pseudomonas aeruginosa.     

A new model of transient complete obstruction of retinal vessels induced by endothelin-1 injection into the posterior vitreous body in rabbits

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by vascular endothelial cells. In order to investigate the effects of ET-1 on retinal vessels, ET-1 (1 1000 pmol) was injected into the posterior vitreous body in rabbits. A high dose of ET-1 induced transient complete obstruction of the retinal vessels. In this experimental model of transient complete obstruction of the retinal vessels, the effects of ET-1 on retinal function were further analyzed by means of electroretinograms. The scotopic a-wave was not affected, but the amplitude of the scotopic b-wave was significantly elevated. The amplitude of oscillatory potentials was significantly reduced. These phenomena suggested that retinal ischemia without choroidal ischemia was brought about due to severe vasoconstriction of the retinal arteries. These findings indicate that intravitreal injection of ET-1 causes a transient cessation of blood supply from retinal vessels and that oscillatory potentials in electroretinograms appear to be sensitive for detecting changes of retinal circulation. This new model of transient complete obstruction of retinal vessels might be useful for studying the pathophysiology of severe retinal ischemia.This work was supported by a grant from the Special Research Project on Circulation Biosystems at the University of Tsukuba     

The diagnostic use of the second oscillatory potential in clinical electroretinography

Of all the electroretinogram (ERG) components (a-wave, b-wave, and oscillatory potentials) only one oscillatory potential, OP₂, was found to be significantly correlated with the absolute intensity of the flash stimulus (i.e., the intensity of the stimulus irrespective of the state of retinal adaptation). Our finding was further confirmed in single cell recordings of lateral geniculate unit activity in rabbits in which peak time of OP₂ was found to correlate better with the geniculate activity. For these reasons we have identified OP₂ as the intensity coding oscillatory potential of the ERG. In order to investigate if this new feature could have some clinical significance, we examined photopic ERGs recorded from patients affected with various retinopathies. In most instances the peak time of OP₂ paralleled that of the b-wave, that is, in the ERG with delayed b-wave the peak time of OP₂ was also delayed, while in ERGs with normal b-wave peak time the peak time of OP₂ was also normal. However, in some conditions (especially in cone-rod diseases) a delayed OP₂ was found in ERGs with normal b-wave peak times.     

Temporal relationship between ERG components and geniculate unit activity in rabbit

The purpose of this study was to examine if there is an ERG component (alpha-wave, b-wave, oscillatory potentials) which can be used to account for the intraretinal processing time. To address this issue, ERGs and LGN unit responses were recorded simultaneously from anesthetized and paralyzed rabbits. A gradual decrease in the intensity of the light stimulus yields a progressive increase in the latency of the LGN unit response. A similar, highly correlated (r = 0.91 +/- 013), latency shift was also noted for one oscillatory potential (OP2). In comparison, correlation coefficients of r = 0.63 +/- 0.27 and r = 0.70 +/- 0.29 were obtained for the alpha- and b-wave respectively. Furthermore, in 77.6% of the cells examined, OP2 preceded LGN unit activity while the b-wave preceded LGN activity in only 17.8% of the cases. Our results suggest that, of all the retinal potentials considered, the peak time of OP2 better reflects the primary visual processes and the intraretinal time taken for visual processing.     

The effect of metoclopramide on the Ganzfeld electroretinogram

Antecedent light flashes enhance the amplitude of the electroretinogram (ERG) oscillatory potentials, but do not modify other ERG responses nor dark-adaptation sensory thresholds. Metoclopramide infusion (i.v.) has a generally attenuating effect on the ERG, which is more evident under conditions of dark- than light-adaptation. Metoclopramide decreases the peak amplitude of the rod b-wave and the dark-adapted cone b-wave in a similar manner; it also significantly increases the implicit time of the rod b-wave, but not of the dark-adapted cone b-wave. In addition metoclopramide reverses the enhancement of the oscillatory potentials by the antecedent light flashes.     

The effect of 2-amino-4-phosphonobutyric acid on the oscillatory potentials of the electroretinogram

Previous reports have shown that an intravitreal injection of 2-amino-4-phosphonobutyric acid, a glutamate analogue that selectively blocks the photoreceptors' input to the on-bipolar cells, produces a rapid decrease in the amplitude of the electroretinographic b-wave. To our knowledge, the effect of this glutamate analogue has not been examined on the oscillatory potentials. We therefore conducted such a study. A needle electrode was inserted into the anterior chamber of the eyes of seven anesthetized and paralyzed rabbits to record simultaneously the electroretinogram and the oscillatory potentials. These responses were evoked by flashes of white light delivered in mesopic conditions. As expected, an injection of 2-amino-4-phosphonobutyric acid, produced a rapid decrease in the amplitude of the b-wave, while the a-wave was relatively spared. The amplitude of the oscillatory potentials also decreased rapidly. At maximal effect, the electroretinogram essentially consisted of a normal a-wave followed by small oscillations and no evidence of a b-wave. The 100–1000 Hz recording confirmed that the oscillations seen on the postinjection electroretinograms were remnants of the original oscillatory potentials.     

The effects of levodopa and haloperidol on flash and pattern ERGs and VEPs in normal humans

We investigated the effects of single doses of the dopamine agonist levodopa and the dopamine antagonist haloperidol on pattern and flash electroretinograms (ERGs) and visual evoked potentials (VEPs) in normal subjects. A placebo and two treatment regimens were administered in a randomized double-masked design. No significant intertreatment differences in the pattern ERGs and VEPs were noted. Although not statistically significant, a clearly discernible tendency was found for increased flash ERG b-wave amplitudes after levodopa administration compared with placebo. In comparison with placebo and levodopa, haloperidol was associated with significantly prolonged flash ERG b-wave implicit times, including each oscillatory potential, which also showed increased duration, particularly in the O1–O3 interpeak implicit time. The failure of pattern ERGs and VEPs to show changes after haloperidol may have been related to the timing of the recordings, which took place during the presumed phase of rising blood levels and before the flash ERG and VEP recordings. Our findings further demonstrated the reliability of the flash ERG in revealing changes in dopaminergic status in the visual system and suggest that steady-state (flicker) ERGs, cone ERGs, and oscillatory potentials have particular use in this regard.Abbreviations C-ERG Cone dominated ERG - M-ERG mixed rod and cone ERG - R-ERG rod dominated ERG - S-ERG steady-state (flicker) ERG - OP oscillatory potential - P-ERG pattern-reversal ERG - F-VEP flash visual evoked potential - P-VEP pattern reversal visual evoked potential - RCT retinocortical time     

影响视网膜脱离患者视网膜功能的因素

目的:评价视网膜脱离患者年龄、病程、视网膜脱离面积、黄斑脱离情况等因素对视网膜功能的影响。方法:将孔源性视网膜脱离(retinal detachment,RD)188例189眼的患者年龄、病程、视网膜脱离面积、黄斑脱离情况、视力与视网膜脱离眼的fERG和mfERG各指标进行相关分析。结果:影响RD眼fERG和mfERG的主要因素是脱离面积、黄斑脱离和视力。以|γ|>0.4,且P≤0.05判定为有相关性。脱离面积与明视和暗适应最大反应ERG a、b波幅值,30Hz闪烁光幅值,OPs波数和幅值负相关;与mfERG象限野P1波幅值密度、幅值负相关。相关系数最高者为fERG暗适应最大反应b波幅值(γ=-0.704)。黄斑脱离与明视和暗适应最大反应ERG b波幅值,30Hz闪烁光ERG幅值负相关;与mfERG环形野环1的P1波幅值密度、幅值负相关,与mfERG象限野P1波幅值密度负相关,相关系数最高者为mfERG环形野环1的P1波幅值(γ=-0.584)。视力与明视和暗适应最大反应a、b波幅值,30Hz闪烁光幅值,OPs子波数和幅值正相关;与mfERG环形野环1的P1波幅值密度、幅值正相关,相关系数最高者为30Hz闪烁光ERG幅值(γ=0.597)。RD眼的fERG异常率最高者为暗适应最大反应ERG b波幅值,异常率为71.3%,视网膜脱离象限野mfERG异常率最高者为P1波幅值,异常率为85.3%。结论:影响RD患者视网膜功能的重要因素是脱离面积和黄斑脱离情况。RD眼对视网膜功能异常反应的mfERG对视网膜功能异常反应的敏感性高于fERG。     

Nontoxic concentration of antibiotics for intravitreal use — evaluated by human in-vitro ERG

The effects of penicillin G (PC-G) sodium, procaine PC-G, cloxacillin sodium (MCIPC), disodium sulbenicillin (SBPC), cefazolin sodium (CEZ), gentamicin sulfate (GM) and fosfomycin sodium (FOM) on the electroretinogram (ERG) of the human in-vitro eye-cup were studied. The oscillatory potentials (OPs) were selectively and greatly suppressed by 1.0mM PC-G sodium. The OPs and c-wave were suppressed by 0.85mM procaine PC-G. The b-wave and OPs were slightly suppressed by 1.0mM MCIPC. The a-wave, b-wave, OPs and c-wave were not deteriorated by 1.0mM SBPC. The OPs appeared to be selectively suppressed by 1.0mM CEZ. The b-wave was suppressed and the peak latencies of the OPs were delayed by 184g/ml (approximately 0.4mM) GM. The amplitudes of the a-wave and c-wave were slightly enhanced and their peak latencies were slightly delayed by 184g/ml GM. The a-wave, b-wave, OPs and c-wave were not deteriorated by 1.0mM FOM. The results of the present study on the human retina were comparable to those on the albino rabbit retina in our previous studies.     

Electroretinographic evaluation in adult diabetics

In cross-sectional fashion, we recorded the maximal combined response and 30-Hz flicker responses in 178 adult diabetics and 40 normal controls according to the recommendations of the International Society of Clinical Electrophysiology of Vision. The oscillatory potentials were extracted from the maximal combined response by high-pass filtering. The clear media and attached retina were criteria for inclusion in this study. The data were statistically analyzed with the expectation that this procedure may provide a new feature that could have some clinical significance. Timing delays occurred more frequently than amplitude reductions in the maximal combined response and flicker responses, while amplitude reductions were more common in the first and second oscillatory potentials. The hypernormal b-wave amplitude was rare. The summed amplitude of the oscillatory potentials was highly correlated with the total power of the oscillatory potentials (the frequency domain). A reduction of the second oscillatory potential amplitude was more common than a reduction of the summed amplitude or total power. The electroretinographic component that demonstrates retinal dysfunction in the earlier stage may be a valuable indicator. In the early stage, a delay in the a-wave time and a reduction in the second oscillatory potential amplitude were the most frequent abnormalities: analysis of variance demonstrated that the summed amplitude of the oscillatory potentials and second oscillatory potential amplitude and time were the most sensitive measures of the diabetic retina. Hence, the second oscillatory potential amplitude may be the most sensitive and valuable indicator representing a quantitative measure of overall retinal dysfunction.     

Abnormal focal macular electroretinograms in eyes with idiopathic epimacular membrane.

PURPOSE: To study the functional state of the retina beneath an epimacular membrane by means of focal macular electroretinography. METHODS: Focal macular electroretinograms of 30 consecutive patients (age 25 to 75 years) with unilateral idiopathic epimacular membrane were recorded prospectively. The amplitudes and implicit times of the a and b waves and the oscillatory potentials (O1, O2, O3) recorded from the eye with idiopathic epimacular membrane were compared with those of the normal fellow eye. RESULTS: There was a statistically significant reduction in the amplitude of the a wave (P < .001), the b wave (P < .001), and the oscillatory potentials (O1 + O2 + O3; P < .001) of the affected eyes. The reduction of the b-wave amplitude was significantly greater than that of the a wave, resulting in a lower b/a wave ratio (P = .003) in the affected eyes. The reduction in the amplitude of the oscillatory potentials was significantly greater than that of the other two components (P < .001). The implicit times were significantly prolonged for the a wave (P < .001), the b wave (P = .004), and 03 (P < .001). There was a significant correlation between relative b-wave amplitude (affected/normal fellow eye) and the visual acuity (r = -0.50, P = .007). These findings were similar to those we reported for eyes with aphakic cystoid macular edema. CONCLUSIONS: The focal macular electroretinograms in eyes with epimacular membrane disclosed abnormalities that were similar to those of eyes with cystoid macular edema. This suggests that the epimacular membrane probably induced damage to the neurons in the inner retinal layers. Dysfunction of these neurons is one possible cause of visual impairment in this disease.     

Oscillatory potential analysis and ERGs of normal and diabetic rats

PURPOSE: To identify and characterize the early alterations of the ERG oscillatory potentials (OPs) under conditions of poor glycemic control associated with diabetes in an animal model. To characterize and correlate the a- and b-wave properties of the ERGs of diabetic animals in parallel with the changes in oscillatory potentials. METHODS: Blood sugars, weights, and ERGs were measured for a group of rats each week for 3 weeks to obtain baseline information. A single injection of streptozotocin was given to the experimental animals. Weights, blood sugar, glycosylated hemoglobin, and detailed ERGs were recorded weekly for up to 12 weeks in control and experimental animals. RESULTS: OP kinetics were found to be inherently related to amplitude. Amplitude-matched OPs were delayed in diabetic animals when compared with baseline data from the same animal. The kinetics of OPs in control animals stayed the same or were slightly accelerated relative to their baseline values. For a given recording condition, OP kinetics were very stable over time and this stability was not disturbed in diabetic animals. Diabetic animals showed a small but significant delay in the a-wave, but no change in b-wave timing. The sensitivity of the b-wave was reduced twofold, but that of the a-wave was not changed. CONCLUSIONS: OPs have been used to evaluate retinal function in both diabetic models and patients. The comparison of amplitude-matched OPs is a robust determinant of changes in kinetics. Researchers and clinicians who use OPs may wish to consider the relationship between OP amplitude and kinetics to avoid confounding assessments of abnormalities. The amplitude versus kinetics relationship does not change form in diabetic animals; it is merely shifted (delayed) on the time axis.     

Correlation of electroretinographic and fluorescein angiographic findings in unilateral central retinal vein obstruction

Background: In central retinal vein obstruction (CRVO), electroretinogram (ERG) abnormalities and extensive retinal capillary dropout (CD) in the fluorescein angiogram (FA) are good indicators of retinal ischemia. We retrospectively studied patients with unilateral CRVO and compared the ERG and FA results Methods: Single white flash ERG, photopic ERG, scotopic ERG and flicker ERG were recordered in 30 cases of unilateral CRVO. We analyzed the correlation between the ERG results and the presence/absence of extensive CD Results: The ERG b/a-wave amplitude ratios, photopic and scotopic b-wave amplitudes, and flicker amplitudes were significantly smaller (P<0.05) in eyes with extensive CD (n=12, 40%), than in eyes without (n=18, 60%). When the photopic or scotopic b-wave amplitudes were normal or supernormal, extensive CD on FA was absent in all eyes. When the b/a-wave ratios were 1.0 or when the b-wave amplitudes with white flash or flicker amplitudes were normal or supernormal, extensive CD was present in less than 32% of eyes Conclusion: These results suggest that the ERG results, especially the b/awave amplitude ratio, are significantly correlated with the presence/absence of CD on FA in CRVO.     

Maturation of the photopic b-wave and oscillatory potentials of the electroretinogram in the neonatal rabbit

We examined the ontogenesis of the b-wave of the rabbit electroretinogram (ERG) in light adaptation and looked at the contribution of the oscillatory potentials (OPs) to the waveform at each stage of development. Recordings were obtained weekly from 2 to 5 weeks of age in six rabbits and every other day during the second week of life in six others. Comparative analysis of the ERGs showed a changing peak time and amplitude of the photopic b-wave with increasing age, consistent with the development of new components corresponding to the OPs. The results illustrate the importance of the OPs in determining both the amplitude and peak time of the photopic b-wave in the maturing rabbit.     

A cyclic adenosine monophosphate agonist elevates the b- and c-waves of the rabbit direct-current electroretinogram

The effects of the stable cyclic adenosine monophosphate analogue adenosine 3, 5-cyclic monophosphorothioate Sp-isomer (Sp-cAMPS) on the direct-current electroretinogram and the standing potential of the eye were studied. Corneal recordings were obtained from unilaterally vitrectomized albino rabbit eyes during alternating intravitreal perfusions with Sp-cAMPS and a control solution (Pharmacia eye irrigating solution). The contralateral eye was used as a control. To evaluate further the effects on the c-wave,in vivo intraretinal microelectrode measurements were made during simultaneous intravitreal perfusion of Sp-cAMPS and irrigating solution, respectively. Sp-cAMPS in concentrations of 1, 10 and 100µM was tested by corneal direct-current electroretinography. There was no significant effect on the a-wave amplitude. The b-wave amplitude was reversibly elevated at an Sp-cAMPS concentration of 100µM (p<0.01, n=7). The c-wave amplitude was reversibly elevated at a concentration of 10µM (p<0.001, n=8), and this effect was more pronounced at 100µM (p<0.001, n=7). The SP increased reversibly at a concentration of 100µM (p<0.001, n=7). Microelectrode recordings were performed with Sp-cAMPS at a concentration of 100µM. The recordings showed significant increases in both the transepithelial potential (p<0.01, n=3) and the slow PIII (p<0.01, n=3). The effects of Sp-cAMPS on the b-wave as well as on the two components of the c-wave suggest influences on both the inner retina and the retinal pigment epithelium of the rabbit eye.Abbreviations PHS Pharmacia eye irrigating solution - AMP adenosine monophosphate - Sp-cAMPS adenosine 3, 5 - cyclic monophosphorothioate Sp-isomer     

Attenuating effects of diazepam on the electroretinogram of normal humans

Response/log I curves were obtained under conditions of dark-and light-adaptation in seven normal male volunteers. For each subject, a baseline electroretinogram (ERG) was recorded. In the same afternoon, a second ERG was obtained after 0.05 mg/kg diazepam, and a third ERG was recorded following 0.10 mg/kg diazepam. Under conditions of dark-adaptation, the following dose-dependent changes were identified: 1) Diazepam attenuated the rod b-wave peak amplitude and increased its implicit time; 2) The dark-adapted longer wavelength cone a-wave and 'blue cone' b-wave showed an increased implicit time; 3) All oscillatory potentials showed an increased implicit time. Under conditions of light-adaptation, dose-dependent decreases in peak amplitude and delays in implicit time were observed for the a- and b-waves. The effects of diazepam on the human ERG were more profound under conditions of light- than dark-adaptation.     

Effects of intravitreal perfusion with dopamine in different concentrations on the DC electroretinogram and the standing potential of the albino rabbit eye

The direct current electroretinogram and the standing potential were recorded from both eyes of 23 albino rabbits during intraocular perfusion of one of the eyes, which was vitrectomized, with a physiologic reference solution (PHS). PHS was then replaced by a test solution containing dopamine dissolved in PHS. The fluids were subsequently alternated (PHS-dopamine-PHS). During irrigation with 0.25–0.5 mM dopamine (11 rabbits) the c-wave amplitude was 140% higher (p < 0.001) and during irrigation with 25 mM dopamine (6 rabbits) 85% lower (p < 0.01) than it was during the corresponding initial perfusion with PHS. The simultaneously recorded b-wave amplitude was reduced (0.25–0.5 mM: -22%, p < 0.001; 25 mM: - 69%, p < 0.001) and the SP level increased (0.25–0.5 mM: +2375 V, p < 0.01; 25 mM: +2530 V, p < 0.05) compared with the values obtained during the corresponding preceding irrigation with PHS. Thus the changes in the b- and c-wave amplitudes during perfusion with dopamine were dependent on the concentration of the drug. In the contralateral control eye (23 rabbits) the c-wave amplitude was 21% higher (p < 0.001), the b-wave amplitude 14% higher (p < 0.001) and the standing potential 1007 V higher (p < 0.001) during intravitreal perfusion with dopamine in the other eye than during the preceding irrigation with PHS in that eye, possibly as a result of increasing dark adaptation.     

Nontoxic concentration of amphotericin B for intravitreal use — evaluated by in vitro ERG

Amphotericin B (AMPH)-induced changes of the electroretinogram (ERG) were studied in the in vitro eye-cup of the albino rabbit. The a-wave, b-wave, oscillatory potentials and c-wave were not changed by 1 M AMPH, and these all were slightly suppressed by 5 M AMPH. These changes were mostly reversible. The b-wave and oscillatory potentials were greatly suppressed by 50 M AMPH. These changes were only partially reversible 75 minutes after re-perfusion without AMPH. Address for offprints Kazuo Kawasaki, M.D., Department of Ophthalmology Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa, 920 Japan.