Electroretinogram B-wave Amplitude Research Articles

Differential Sensitivity of Cones to Iron-Mediated Oxidative Damage

In this study, the hypothesis that increased intraocular levels of iron cause oxidative damage to the retina was tested. Adult C57BL/6 mice were given an intravitreous injection of saline or 0.10, 0.25, or 0.50 mM FeSO(4). Scotopic electroretinograms (ERGs) were performed 3, 7, and 14 days after injection, and photopic ERGs were performed on day 14. Hydroethidine was used to identify superoxide radicals and lipid peroxidation was visualized by staining for hydroxynonenal (HNE). Retinal cell death was evaluated by TUNEL and measurement of inner nuclear layer (INL) and outer nuclear layer (ONL) thickness. Levels of rhodopsin and cone-opsin mRNA were measured by quantitative real time RT-PCR. Cone density was assessed by peanut agglutinin staining and confocal microscopy. Compared with retinas in saline-injected eyes, retinas from eyes injected with FeSO(4) showed greater fluorescence after intravenous injection of hydroethidine due to superoxide radicals in photoreceptors, greater photoreceptor staining for HNE, a marker of lipid peroxidation, and increased expression of Heme oxygenase 1, an indicator of oxidative stress. ERG b-wave amplitudes were reduced (photopic > scotopic) in FeSO(4)-injected eyes compared with those in saline-injected eyes. Numerous TUNEL-stained nuclei were seen along the outer border of the ONL, the location of cone cell nuclei, at 1 and 2 days after injection of FeSO(4). In FeSO(4)-injected eyes, the thickness of the ONL, but not the INL, was significantly reduced, and 17 days after injection, there were 3.8- and 2.6-fold reductions in the mRNAs for M-cone and S-cone opsin, respectively, whereas there was no significant difference in rhodopsin mRNA. Confocal microscopy of peanut agglutinin-stained sections showed dose-dependent FeSO(4)-induced cone drop out. Increased intraocular levels of FeSO(4) cause oxidative damage to photoreceptors with greater damage to cones than rods. This finding suggests that the oxidative defense system of cones differs from that of rods and other retinal cells, and that cones are more susceptible to damage from the type of oxidative stress imposed by iron.

A Ni2+-sensitive component of the ERG b-wave from the isolated bovine retina is related to E-type voltage-gated Ca2+ channels

Voltage-dependent Ca(2+) channels trigger and control important cellular processes like neurotransmitter release and secretion, long-term potentiation, and gene expression in excitable cells. During retinal signal perception and processing, presynaptic Ca(2+) channels facilitate neurotransmitter release in photoreceptors and bipolar neurons, at nonspiking synapses which generate graded potentials. The nature of voltage-gated Ca(2+) channels involved in retinal signal transduction is investigated in the present report by recording the electroretinogram (ERG) from the isolated and perfused bovine retina. Transcripts of the E/R- and T-type Ca(2+) channels are detected by RT-PCR. Using the Ca(2+) channel antagonists (+/-)-isradipine, NiCl(2), mibefradil, and SNX-482 results in either stimulatory or inhibitory effects on the ERG b-wave amplitude. On the transcript level, mRNA is detected for the E/R-type and a T-type voltage-gated Ca(2+) channel containing Ca(v)2.3 and Ca(v)3.1 as ion-conducting subunits, respectively. Blocking of the E/R-type Ca(2+) channels by NiCl(2) (10 microM) and SNX-482 (30 nM) contributes to the stimulatory effect, whereas antagonism of T-type as well as L-type Ca(2+) channels meditates the inhibitory action on the b-wave amplitude. Thus, a novel function for E/R-type voltage-gated Ca(2+) channels is probably associated with the visual signal transduction in the mammalian retina.

Effects of the intravitreal administration of dopaminergic ligands on the b-wave amplitude of the rabbit electroretinogram

In the retina of mammals, dopamine (DA) is generally released by amacrine cells and is known to alter the physiology of most retinal cells. It is well known that DA reduces the amplitude of the b-wave of the electroretinogram (ERG) in rabbit. However, the specific receptor subtypes that mediate this action have not yet been elucidated. To do this, we recorded flash ERGs before and after the intravitreal injection of D 1-like DA receptor agonists (SKF38393, A77693) and antagonist (SCH23390), and of D 2-like agonist (R(−)-propylnorapomorphine hydrochloride; NPA) and antagonist ((S)-(−)-sulpiride). Contralateral control eyes were injected with the vehicle only. Both D 1 agonists provoked a reduction of the ERG b-wave amplitude (34.0% and 59.2% of the pre-injection level, respectively). The D 2-like agonist NPA had no significant effects on ERG components. Unexpectedly, both D 1- and D 2-like antagonists also reduced the b-wave amplitude (28.9% and 59.8%). Overall, these data suggest that the previously described effect of DA on the rabbit ERG b-wave came from activation of D 1-like receptors. On the basis of the effects observed with D 2-like antagonist, a subtle contribution of D 2-like presynaptic receptors cannot be ruled out.

Topical instillation of ciliary neurotrophic factor inhibits retinal degeneration in streptozotocin-induced diabetic rats.

Intraocular injections of ciliary neurotrophic factor (CNTF) or intraocular adenovirus-mediated CNTF gene transfer have been reported to inhibit retinal alterations in inherited retinal degeneration in mice strains. To investigate whether or not CNTF administered by eye drops prevents retinal degeneration in streptozotocin (STZ)-induced diabetic rats, recombinant CNTF was administered to eyes of diabetic rats (n=20) twice daily for 1 month after the onset of diabetes. The b-wave amplitude of electroretinogram in CNTF-administered diabetic rats was significantly larger than that of diabetic rats, and approached that of the controls. Atrophy of the inner plexiform layer, and cavity formation in the pigment epithelium, which were observed in diabetic rats, were prevented in CNTF-administered diabetic rats. These results indicate that CNTF administration by eye drops prevents retinal degeneration in STZ-induced diabetic rats.

Circadian rhythm of iguana electroretinogram: the role of dopamine and melatonin.

The amplitude of the b-wave of the electroretinogram (ERG) varies with a circadian rhythm in the green iguana; the amplitude is high during the day(or subjective day) and low during the night (or subjective night). Dopamine and melatonin contents in the eye are robustly rhythmic under constant conditions; dopamine levels are high during the subjective day, and melatonin levels are high during the subjective night. Dopamine and melatonin affect the amplitude of the b-wave in an antagonistic and phase-dependent manner: dopamine D2-receptor agonists injected intraocularly during the subjective night produce high-amplitude b-waves characteristic of the subjective day, whereas melatonin injected intraocularly during the subjective day reduces b-wave amplitude. Sectioning the optic nerve abolishes the circadian rhythms of b-wave amplitude and of dopamine content. The results of this study suggest that in iguana, a negative feedback loop involving dopamine and melatonin regulates the circadian rhythm of the ERG b-wave amplitude that is at least in part generated in the brain.

Long-Term Intake of trans (n-3) Polyunsaturated Fatty Acids Reduces the b-Wave Amplitude of Electroretinograms in Rats

Weanling rats were fed three diets differing in their concentrations of the cis- and trans-isomers of alpha-linolenic acid [18:3(n-3)] for 12 mo to study the long-term effects of these fatty acids on the electroretinogram (ERG). The diets contained 18:3(n-3) in its natural form at 2.0 g/100 g total fatty acids (C group), partially isomerized 18:3(n-3) [1.3 g/100 g cis 18:3(n-3) + 0.7 g/100 g trans 18:3(n-3); cT group] and the control level of cis 18:3(n-3) with trans 18:3(n-3) [2.0 g/100 g cis 18:3(n-3) + 0.7 g/100 g trans 18:3(n-3); CT group]. The ERG and the levels of trans-isomers of the polyunsaturated fatty acids (PUFA) of retinal and hepatic phospholipids were determined after 3, 6, 9 and 12 mo of feeding the experimental diets. Dietary trans alpha-linolenic acid altered the fatty acid composition of retinal and hepatic phospholipids by significantly increasing the Delta19trans-isomer of docosahexaenoic acid. Moreover, dietary trans-isomers of alpha-linolenic acid significantly decreased the b-wave amplitude of the ERG by 9 mo of feeding. We conclude that long-term intake of small amounts of trans-isomers of alpha-linolenic acid could disturb visual function. However, further studies are required to determine the mechanisms responsible for this phenomenon.

Evaluation of different recording parameters to establish a standard for flash electroretinography in rodents

Different electrodes and stimulus protocols commonly used for electroretinography in rodent eyes were compared for convenience of use, degree of damage to corneal epithelium, and for magnitude of amplitude, reproducibility, left versus right eye accuracy, and reliability of recorded parameters of the flash electroretinogram (ERG). Adult C57BL/6 pigmented mice and albino Wistar rats were used to determine scotopic ERGs in response to Ganzfeld or strobe-light stimulation and light-adapted (photopic) ERGs recorded from both eyes at the same time. Test–retest data were used for statistical analyses to compare a monopolar gold-wire contact lens electrode (CLE), a cotton-wick silver–silver chloride electrode (CSCE), a DTL fiber electrode (DTLE), and a circular stainless steel wire electrode (SSE). Corneas were evaluated for abrasion after ERG recordings using fluorescein staining and also for the time taken, ease of insertion, and re-insertions required for the different electrodes. Compared to CSCE, DTLE, and SSE, the ERG potentials recorded by CLE had significantly larger scotopic amplitudes and oscillatory potentials under strobe or Ganzfeld stimulation and for light-adapted ERG b-wave amplitudes in both mice and rats. In analyzing test–retest data of scotopic ERG a-wave and b-wave amplitudes, the intraclass correlation coefficient showed the best agreement for the CLE (range 0.61–0.94) compared to the SSE (0.13–0.77), DTLE (0.02–0.69), and CSCE (0.12–0.51). In mice and rats, logistic regression analyses revealed significant correlations for amplitudes of most scotopic ERG parameters between contralateral eyes obtained with CLE and for some ERG components recorded by SSE. When comparing ERG amplitudes for stimulation by strobe or Ganzfeld, the difference was least with the CLE compared to DTLE, CSCE, or SSE. The time taken to insert the four different electrodes was greatest for the CLE in both mice and rats. The extent of corneal abrasion resulting from electrode use in mice was largest for the SSE followed by the CLE. However, in rats there was almost no corneal damage after ERG recordings with the CLE. Because of the stability of eye contact, the CLE allows ERGs to be determined over a longer recording session. Recording of scotopic and photopic (light-adapted) ERGs in rodents with monopolar gold-wire contact lens electrodes provides greater amplitudes and higher reproducibility when compared to other commonly used corneal electrodes. These electrodes are significantly better overall than others that were evaluated and should be considered for a standard protocol to monitor retinal function in rodent eyes.

Inflammatory Response in Experimental Staphylococcus andPseudomonas Endophthalmitis

Staphylococcus epidermidis [2.0 × 10⁴ colony-forming units (CFU)/0.1 ml] and Pseudomonas aeruginosa (2.0 × 10³ CFU/ml) were inoculated in the vitreous humor of rabbits. In S. epidermidis endophthalmitis, the numbers of microorganisms reached a maximum (4.1 × 10⁷ CFU/ml) at day 2 after inoculation and then declined spontaneously. However, clinical scores were observed to be worst at day 5. In P. aeruginosa endophthalmitis, the numbers of microorganisms reached a maximum (9.3 × 10⁶ CFU/ml) 36 h after inoculation. However, culture results were persistently positive until day 15. Electroretinogram (ERG) b-wave amplitudes in S. epidermidis endophthalmitis continued to decrease from day 3 (>24%) until day 5, and then recovered to the preinoculative level of amplitudes at day 7. ERG b-wave amplitudes in P. aeruginosa endophthalmitis continued to decrease after 24 h (>24%). ERG b-wave amplitudes from day 7 to day 15 were flat. The inflammatory response continued under the absence of microorganisms in S. epidermidis endophthalmitis. The time in which a maximum in the number of microorganisms was reached was earlier than that in the clinical examination scores in both S. epidermidis and P. aeruginosa endophthalmitis.

Mitochondrial maculopathy: geographic atrophy of the macula in the MELAS associated A to G 3243 mitochondrial DNA point mutation

PURPOSE: To report ocular findings in the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome) in a family with the A to G 3243 mitochondrial (mt) DNA point mutation.METHODS: Case reports. Ocular findings are described from four family members with the MELAS associated A to G 3243 mt DNA point mutation.RESULTS: Findings included ophthalmoplegia, neurosensory deafness, reduction of photopic and scotopic electroretinogram b-wave amplitudes, and myopathy, as well as macular retinal pigment epithelial atrophy. No family members had nyctalopia, attenuation of retinal blood vessels, or retinal bone spicule pigmentation.CONCLUSION: The finding of slowly progressive macular retinal pigment epithelial atrophy expands the reported phenotypic diversity of patients with A3243G mt DNA mutations. MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) is a maternally inherited disorder associated with abnormal mitochondria, manifesting in tissues highly dependent on oxidative metabolism. Ocular changes in MELAS syndrome have included reversible scotomata, ophthalmoplegia, pigmentary retinopathy, marked attenuation of the scotopic electroretinogram, myopia, and nuclear cataract.1,2We highlight some of these ocular manifestations in a family with MELAS syndrome and describe a distinct maculopathy. A 48-year-old woman was referred for evaluation of an asymptomatic maculopathy. Her medical history included mild sensorineural hearing loss; her family history included a mother with congestive heart failure, diabetes mellitus, ophthalmoplegia, and parafoveal atrophy as well as a deceased brother who had an unknown ocular disease, deafness, diabetes, and heart failure. Ocular examination disclosed best-corrected visual acuities of RE: 20/25 and LE: 20/30, normal results from Ishihara color plate testing, significant limitation of gaze in all fields (as much as 70% of expected), and several patches of macular retinal pigment epithelial atrophy bilaterally, which were noted to have become slightly larger compared with fundus photographs taken 8 years earlier. These regions of atrophy correlated with scotomata on Amsler grid and visual field testing (Figures 1 and 2). Her electroretinogram disclosed reduction of photopic and scotopic b-wave amplitudes with normal implicit times. Screening for mitochondrial disorders was suggested but refused by the patient.Several months later, the patient’s sister was diagnosed with MELAS syndrome after presenting with stroke; she was found to have bilateral neurosensory deafness, bicuspid aortic valve, and diabetes mellitus, and a muscle biopsy was positive for ragged red muscle fibers. She was noted to have ophthalmoplegia but did not have ophthalmic complaints. No family members had nyctalopia, waxy pallor of the optic nerve, or attenuation of the retinal vessels. The four tested members of the family, including the sister with MELAS syndrome as well as the original patient and her daughter and son, were found to have the A to G 3243 mt DNA mutation heteroplasmic with wild-type mt DNA.This report amplifies and corroborates some of the ophthalmic features of MELAS syndrome by describing geographic atrophy of the macula in families with the syndrome. The symptoms associated with MELAS syndrome typically appear in childhood and often cause death by the fourth decade.3 Two mt DNA mutations have been associated with this syndrome and are both located in the tRNAleu (UUR) gene. In 80% of cases, the mutation is an A to G transition at mt-3243, and in 10% of cases, the mutation is an A to G transition at mt-3271.4 Many maternal relatives of patients with MELAS syndrome exhibit a scarcity of symptoms secondary to the presence of “heteroplasmy,” a mixture of mutant and wild-type intracellular mitochondria. The mutant phenotype is expressed only when an intracellular threshold of mt DNA has been reached. Mitochondrial mutation is uncommon in the general population; however, patients with the mutation were recently shown to have a wider range of phenotypic diversity than previously reported.5 Nutritional supplementation should be considered, although no large, well-designed trial has studied its efficacy.1 Atrophic macular pigment epithelial atrophy associated with motility disorders and deafness should precipitate an evaluation for mitochondrial disorders.

Electrophysiological findings in Stargardt's-fundus flavimaculatus disease.

To determine the incidence of electrophysiological abnormalities in patients with Stargardt's-fundus flavimaculatus (STGD/FFM) disease. A retrospective review was carried out of the hospital records of 46 patients who had undergone a scotopic, single flash photopic and 30 Hz electroretinogram (ERG), pattern ERG (PERG) and electro-oculogram (EOG). Patients were classified in two groups: those with flecks (n = 26) and those without flecks (n = 20). The incidence of abnormalities (amplitude and/or latency) for the two groups was: PERG, 90% and 98%; 30 Hz ERG, 55.8% and 50%; scotopic ERG, 38.5% and 27.5%; and single flash photopic ERG, 26% and 16%, respectively. EOG abnormalities occurred significantly more frequently in the group with flecks compared with the group without flecks: 69% and 42.5% respectively (p < 0.025). Furthermore, in the group with flecks the group mean scotopic ERG b-wave, 30 Hz ERG b-wave and PERG (P50) amplitude were significantly lower than in the group without flecks (p < 0.01). The most consistent electrophysiological abnormality in STGD/ FFM is the reduction of the PERG. However, EOG, 30 Hz ERG, scotopic and photopic ERG abnormalities can also frequently occur. ERG and EOG abnormalities occur more often in the presence of flecks.

Cone Electroretinograms in Response to Color Stimuli After Successful Retinal Detachment Surgery

Cone electroretinograms (ERGs) in response to different color flashes were examined using a Ganzfeld stimulus in 19 eyes after successful retinal detachment surgery. In the operated eyes, the short wavelength sensitive (S-) cone b-wave was reduced more than the mixed long (L-) and middle (M-) wavelength sensitive cone b-waves. The ratio of the S-cone ERG b-wave amplitude between operated eyes and fellow eyes was significantly lower than the L- and M-cone ERG b-waves ( P < .01). These ERG results indicated that the S-cone system is more impaired than the L- and M-cone systems after retinal detachment surgery.

ERG Abnormalities in Relation to Histopathologic Findings in Vitiligo Mutant Mice

The vitiligo,mivit, mutation has several prenatal and perinatal effects on development of the retinal pigment epithelium, and later, leads to extensive, progressive degeneration of photoreceptor cells in the neural retina of homozygous affected mice. The aim of the present study was to determine by functional criteria how early can abnormalities be detected in the neural retina. Electroretinograms (ERGs) were correlated with histopathological findings in the same animals. Congenic homozygous mutants, heterozygotes, and homozygous wild-type mice were studied at 2, 3, 6, 24 and 56 weeks of age, the same animals being tested serially at the three older time points. The nontested eye of each animal was embedded in Epon and sectioned at 1 μm for light microscopic study. ERG recordings from vitiligo homozygotes differed from heterozygous and wild-type mice, but the latter two groups did not differ from each other. As early as two weeks of age, homozygous mutants showed a significant reduction of rod dominated maximum ERG a-wave and b-wave amplitude. ERG b-wave sensitivity (σ) was significantly reduced, and ERG implicit times were delayed for homozygous mutants at 3 (a-wave) and 6 (b-wave) weeks of age. This is the first study to report reduced and delayed ERG a-waves and b-waves in this animal model, like the early functional abnormalities in human retinitis pigmentosa, and also the first to show short and disoriented rod outer segments, beginning retinal separation from the pigment epithelium, and a few macrophage-like cells already present in the subretinal space at 2 weeks of age (in three of four homozygous mutant eyes examined). Given these early functional and structural abnormalities in the neural retina, it remains to be determined whether themigene targets the retinal pigment epithelial cell, the photoreceptor cell, or both.

Hepatic Retinopathia. Changes in Retinal Function

In patients suffering from hepatic failure, the brain is subject to defined morphological and functional changes known as hepatic encephalopathia (HE). The morphological changes are dominated by glial cells (Alzheimer-type II astrocytes). It has recently been possible to demonstrate, that the retinal glia (Müller) cells undergo similar morphological changes. The present study was carried out in order to reveal if these Müller cell changes cause any characteristic functional deficits. We examined 11 patients with different stages of HE due to liver cirrhosis. Six patients were at stage 0 or 1 (group I) and five at stage 2 or 3 (group II). They underwent ophthalmological routine examination, colour vision testing and standard ERG recording. None of the patients reported impaired vision, in daylight or at night. There were no fundus abnormalities except very mild changes of the pigment epithelium and abnormal reflexes of the inner limiting membrane, especially in the higher HE stages. The number of confusions in the colour arrangement test increased with the higher stages of HE, preferably in the tritan axis. The scotopic a- and b-waves of the electroretinogram (ERG) were almost unchanged in group I and significantly decreased and delayed in group II. The photopic ERG b-wave amplitudes were changed in a similar fashion. Oscillatory potentials proved to be most sensitive to hepatotoxic changes. Their latencies were significantly delayed even in group I. Amplitudes were decreased significantly only in group II. Patients suffering from hepatic failure and accompanying HE display functional abnormalities of the retina. These are best demonstrated by the ERG, and correlate well with the degree of HE. A hypothesis is presented that relates the observed functional changes to altered neurotransmitter levels and impaired retinal glial-neuronal interaction, due to Müller cell damage caused by elevated ammonia levels. © 1997 Elsevier Science Ltd.

An intravitreal device providing sustained release of cyclosporine and dexamethasone.

A device that releases cyclosporine and dexamethasone into the eye for extended periods of time might be beneficial in diseases such as proliferative vitreoretinopathy and uveitis. In this study we examine the pharmacokinetics and toxicity of cyclosporine and dexamethasone combined in an intravitreal sustained-release device and the toxicity of a similar device containing only dexamethasone in rabbits. Rabbits were divided into three groups for (1) evaluation of the drug tissue levels and device release kinetics following implantation of a device containing 100 micrograms of cyclosporine labeled with 2 microCi of 3H-cyclosporine and 2 mg of dexamethasone; (2) evaluation of the toxicity of this intravitreal device; and (3) evaluation of the toxicity of a similar device containing 2 mg of dexamethasone only. Cyclosporine was measured using a scintillation counter and dexamethasone was measured by high pressure liquid chromatography (HPLC). Toxicity was evaluated by electroretinography, clinical examination, and light microscopy. Vitreous concentrations of cyclosporine (+/- standard deviation) averaged 0.06 (+/- 0.02) microgram/ml over 10 weeks. The average dexamethasone concentration over the 10 week period was 2.9 (+/- 0.9) micrograms/ml. Devices containing cyclosporine and dexamethasone released each drug at rates similar to devices containing cyclosporine or dexamethasone alone. Devices containing both cyclosporine and dexamethasone caused reversible depressions in the b-wave amplitude of photopic and scotopic electroretinograms (ERG's). There was no evidence of toxicity associated with the devices containing dexamethasone only. There was no drug-related toxicity evident on clinical or histopathologic examination of eyes with devices containing the combination of cyclosporine and dexamethasone or dexamethasone alone. We conclude that the device maintains potentially therapeutic levels of both cyclosporine and dexamethasone in the vitreous. Reversible electroretinographic abnormalities are attributable to cyclosporine. A sustained-release device containing cyclosporine and dexamethasone may be useful for reducing inflammation in diseases such as proliferative vitreoretinopathy and uveitis.

Effects of hypoxemia on the electroretinogram in diabetics.

To identify any relationship between retinal dependence on oxygen and the presence or absence of retinopathy in a group of patients with the same duration of diabetes, based on the proposal that diabetic retinopathy results from long-term adaptation to the Crabtree effect, i.e., reduction of oxidative phosphorylation caused by increased intracellular glucose concentrations. Electroretinograms were recorded on 17 patients with insulin-dependent diabetes (of 15 to 17 years duration) and 10 healthy controls. Recordings were made under normal conditions and then after 4 min of hypoxemia (oxygen saturation, 80%). Retinopathy status was assessed from fundus photographs. Electroretinogram b-wave amplitudes of seven patients without retinopathy were reduced to 69% by the hypoxemia compared to a reduction to 88% for 10 patients with retinopathy (p = 0.039). The relative sensitivity to hypoxemia of patients without retinopathy suggests greater dependence on oxidative phosphorylation than in patients with retinopathy. The results appear to be consistent with the Crabtree effect hypothesis. Downregulation of tissue oxygen consumption by the Crabtree effect would lead to a reduction of retinal blood flow by autoregulation and to a reduced concentration of adenosine triphosphate in the retina.

Safety of intravitreally injected ciprofloxacin in phakic rabbit eyes

This study was designed to determine the maximal safe drug concentration of intravitreal ciprofloxacin in phakic rabbit eyes. Twenty-two eyes of New Zealand pigmented rabbits received midvitreal ciprofloxacin of 100, 200, 400, 600 or 800 micrograms in BSS Plus, or BSS Plus only. Retinal toxicity was dose-dependent as determined with electroretinography, light microscopy, and transmission electron microscopy. At a dose of greater than 400 micrograms, disorganization of the outer segments was a main pathological finding in transmission electron microscopy. We evaluated retinal function by measuring the electroretinograms for a graded series of flash intensities and by fitting electroretinogram b-wave amplitudes to the Naka-Rushton equation. At a dose of greater than 600 micrograms, Rmax was significantly decreased and log K was significantly increased. N-value tended to decrease. A decrease of b-wave amplitudes caused by retinal toxicity could be detected very sensitively with lower luminance stimuli. Determination of retinal toxicity with lower luminance electroretinography revealed a significant decrease of b-wave amplitudes at a dose of greater than 400 micrograms. We concluded that a safe dose of intravitreal ciprofloxacin in phakic rabbit eyes was 200 micrograms in phakic eyes.

Evaluation of methanol-induced retinotoxicity using oscillatory potential analysis

Methanol is an ocular toxicant which causes visual dysfunction often leading to blindness after acute exposure. While the manifestation of the toxicity has been widely studied, the mechanism by which the injury is produced is still uncertain. A major unanswered question pertains to the site of action, i.e. direct retinotoxicity versus primary optic nerve toxicity with secondary retinotoxicity. In the present study, the effect of methanol on the oscillatory potentials (OPs) of the electroretinogram (ERG) were evaluated in acutely treated folate sufficient (FS) and folate reduced (FR) Long-Evans rats. The OP amplitudes of the acutely dosed FR rats displayed non-selective decreases in all OP amplitudes and non-selective increases in all OP latencies at methanol doses ranging from 1.5 to 3.0 g/kg. Comparing decreases of op 2 and ERG b-wave amplitudes with blood formate concentration demonstrates that the b-wave is more sensitive than op 2 in a blood formate concentration range of 6–14 mM, suggesting that retinal ischemia is not involved in methanol-induced visual system toxicity.

The effects of acetazolamide in albino rabbits, pigmented rabbits, and humans

In three separate experiments albino rabbits, pigmented rabbits, and humans were tested following administration of acetazolamide and without acetazolamide. In all three experiments, we recorded electroretinograms (ERGs) under dark adapted and light adapted conditions and measured the b-wave amplitudes. Dark adapted ERG b-wave amplitudes were increased following administration of acetazolamide as compared to control conditions, in albino rabbits, pigmented rabbits and humans. Light adapted b-wave amplitudes showed no statistically significant changes as a function of acetazolamide administration although in all three experiments there was a trend toward light adapted b-wave amplitude reduction following administration of acetazolamide. In the human experiments, ERG a-wave amplitudes were also measured. Light adapted a-wave amplitudes were reduced following administration of acetazolamide. In the human experiments, several behavioral tests were performed, including L' Anthony desaturated D-15, Farnsworth-Munseu 100 hue, Cogan-Gunkel chromatograph, Nagel anomaloscope, Goldmann-Weckers dark adaptometry. There were no consistent changes in the human dark adaptation thresholds or color discrimination, although several measures approached significance.

The effects of dopamine blockade on the human flash electroretinogram.

Single-cell electrophysiologic studies have shown that dopamine modulates retinal activity, but its role in human retinal processing is unclear. We investigated the effects of short-term oral administration of dopaminergic receptor blocking agents on the flash electroretinogram in humans. Both chlorpromazine (25 and 50 mg) and fluphenazine (1 and 2 mg) significantly reduced electroretinogram b-wave amplitudes and also selectively reduced the amplitude of the first oscillatory potential. Implicit times were not altered. Metoclopramide (10 and 20 mg) had no effect on any electroretinographic variable. Our study indicates that dopamine receptor blocking agents with both D-1 and D-2 receptor affinities reduce the amplitude of the electroretinogram in humans.

Acetyl-L-Carnitine Corrects Electroretinographic Deficits in Experimental Diabetes

Acetyl-L-carnitine reduces the latencies of electroretinogram oscillatory potentials in healthy humans. The effect of acetyl-L-carnitine (50 mg.kg-1.day-1) on the increased electroretinogram latencies found in rats with STZ-induced hyperglycemia of 3-wk duration was evaluated. The aldose reductase inhibitor sorbinil, which has been shown to normalize abnormal electroretinogram tracings associated with STZ-induced diabetes, was used as a positive control. Aldose reductase inhibitors are thought to lower tissue sorbitol while increasing myo-inositol. The electroretinograms of the STZ-induced diabetic rats in this study were abnormal; treatment with acetyl-L-carnitine as well as sorbinil significantly improved electroretinogram b-wave amplitude and decreased the latencies of oscillatory potentials 2 and 3. Acetyl-L-carnitine treatment of STZ-induced diabetic rats did not affect hyperglycemia or erythrocyte polyol pathway activity as reflected by erythrocyte sorbitol levels. In contrast, sorbinil did reduce elevated erythrocyte sorbitol levels. This suggests that the impaired electroretinograms associated with STZ-induced diabetes may not be caused solely by increased polyol pathway activity.