Electroretinogram Measurements Research Articles

Human Cone Pigment Expressed in Transgenic Mice Yields Altered Vision

Genetically driven alterations in the complement of retinal photopigments are fundamental steps in the evolution of vision. We sought to determine how a newly added photopigment might impact vision by studying a transgenic mouse that expresses a human cone photopigment. Electroretinogram (ERG) measurements indicate that the added pigment works well, significantly changing spectral sensitivity without deleteriously affecting the operation of the native cone pigments. Visual capacities of the transgenic mice were established in behavioral tests. The new pigment was found to provide a significant expansion of the spectral range over which mice can perceive light, thus underlining the immediate utility of acquiring a new photopigment. The transgenic mouse also has the receptor basis for a novel color vision capacity, but tests show that potential was not realized. This failure likely reflects limitations in the organizational arrangement of the mouse retina.

Characterization of multi-input electroretinogram using normal control subjects

The multi-input electroretinogram (ERG) has recently been developed to analyze focal retinal responses in the central region and is expected to become a powerful tool for management of retinal diseases. The relationship between the obtained ERG response and retinal neuronal functions is not yet fully understood. In the present study, in order to study the spatial retinal functions; multi-input ERGs were recorded from 14 healthy subjects under several illumination conditions modulating photoreceptor functions. The first-order kernel amplitudes were changed in correspondence to the cone photoreceptor adaptation states under different background illuminations. A strong flash exposure significantly lowered the amplitude (approximately 70%) within the central 15 deg but lowered it only slightly (10-20%) in the peripheral areas outside the central 15 deg. Similar effects were observed when the stimulus luminance was lowered by neutral density filters. Our data suggest that a newly developed multi-input measurement of ERGs represents signals within the firing of postreceptor neurons from cone photoreceptors at specific areas. Thus, this analysis is a useful tool for mapping the spatial network of neurons in the central region.

Chromophore distribution and ultraviolet visual pigment in the compound eyes of the Japanese fireflies Luciola cruciata and L. lateralis (Coleoptera, Lampyridae)

Based on electroretinogram measurements, fireflies are reported to possess two spectral-sensitivity peaks: one in the near-ultraviolet and the other in the green region. This suggests that at least two kinds of visual pigment should be present (Lall and Lloyd 1989). Analyses by high pressure liquid chromatography revealed that there are two kinds of chromophores, i.e., retinal (A1) and 3-hydroxyretinal (A3), in the compound eye of Japanese fireflies of the genus Luciola (Gleadall et␣al. 1989). Through selective light-adaptation experiments and in vitro analyses by high pressure liquid chromatography, it is demonstrated that the A1 is the chromophore of an ultraviolet-sensitive visual pigment and the A3 is the chromophore of a green-sensitive pigment. The absolute amounts of A1 and A3 were, respectively, 32.1 ± 3.9 and 111.1 ± 35.2 pmol in male, and 26.9 ± 6.9 and 63.4 ± 18.2 pmol in female (mean ± SD per animal). These results indicate that the amount of green-sensitive visual pigment in males is significantly higher than in females. A difference in the distribution of these chromophores is demonstrated in the eyes of female (but not male) fireflies: in the dorsal region of the female eye, the A1:A3 ratio is higher than that for the rest of the eye.

Kinetics of rhodopsin regeneration in situ and in the excised median eye of Limulus polyphemus measured using electrophysiological methods.

The reactivation of rhodopsin after photoregeneration from metarhodopsin in the UV-sensitive cells of the median eye of Limulus was examined by means of extracellular electroretinogram (ERG) measurements. Absorbed photons convert the transducing rhodopsin (Rt) to metarhodopsin, which is thermostable and can be reconverted by another photon to non-transducing rhodopsin (Rn). The amplitude of the ERG is assumed to correlate linearly with the amount of Rt under otherwise constant conditions. The results demonstrate that the reactivation of Rn recorded in vivo in the intact animal is much faster than that in the excised eye [half period: 4 min (in vivo), 24 min (excised eye)]. In the excised eye the ERG amplitudes recover over a sigmoidal time course; however, in vivo the kinetics often appear to be exponential. The in vivo kinetics were measured by several defined molar ratios of Rn to rhodopsin plus metarhodopsin [Rn/(R + M)]. These were adjusted by different durations of pre-illumination with UV light, which is preferentially absorbed by rhodopsin. The in vivo kinetics were fitted by a single exponential function. At very high molar ratios of Rn (> 90%) the kinetics become sigmoidal even in the in vivo experiments. The half-life of the in vivo kinetics depends linearly on the initial molar Rn/(R + M) ratio [half-life: 4-12 min with a rise of 0.1 min/% inactivated metarhodopsin (Mn), 20 degrees C]. The results are consistent with the assumption of multiple-step dephosphorylation being the rate-limiting step in regeneration of rhodopsin in the dark.

Transient Fluctuation of Serum Melatonin Rhythm is Suppressed Centrally by Vitamin B

Vitamin B12 has been reported to improve sleep-wake rhythm disorders. Although the mechanism is still unclear, a change in the sensitivity of the circadian clock system to photic input is thought to be a possible mechanism of the effect. In this study, the effect of the vitamin B12 on the circadian aspect of the electroretinogram (ERG) and serum melatonin level was analyzed in rats. Vitamin B12, α-(5,6-dimethylbenzimidazolyl)-co-methyl-cobamide was daily administrated subcutaneously for 8 weeks to adult male Wister rats in the experimental group, and saline was given to the control group. The ERGs were recorded under dark adaptation during the night and day, and under light adaptation (0.1 lux) during the night. Blood was drawn before and after ERG recording. The amplitudes of the a-wave, fc-wave, and trough-to-peak of both waves and latencies of ERG were analyzed following various exposures to stimuli of light intensity. These parameters in the group treated with vitamin B12 showed similar characteristics to the control group, and no significant difference was observed between the two groups. The melatonin levels of both groups before the measurement of ERG were similar under each measurement condition. The elevated serum melatonin concentration in the control group under dark adaptation at night was suppressed after the series of 10-msec light stimuli used for measurement of ERG. However, this suppressing effect of light pulses on melatonin level was significantly inhibited in the group treated with vitamin B12. Under light adaptation during the night and under dark adaptation during the day, melatonin levels after the measurement of ERG were not different between the groups. From these results, it is suggested that vitamin B12 is effective in suppressing melatonin rhythm disturbances introduced by transient light stimulation, and it affects the site more central than the retinal level. (Chronobiology International, 14(6), 549–560, 1997)

Long-term effects of fenretinide on retinal function

The long-term effects of the synthetic retinoid fenretinide (4-HPR) on retinal function were studied by electroretinogram (ERG) in 24 women treated for a median of 30.5 months and in 18 untreated controls belonging to a phase III intervention trial. The six outcome measures were: a wave implicit time, peak-to-peak amplitude and implicit time of b wave following both cone stimulation and maximal cone-rod stimulation in the dark-adapted eye. Multivariate analysis of covariance was applied to evaluate the joint effect on the whole set of ERG measures taking into account their inter-relationship. Predictive factors with a significant effect on ERG measures were: (1) a qualitative interaction between age and treatment duration and (2) the squared (parabolic) function of plasma retinol. Individually, the b wave implicit time following cone stimulation was the only ERG measure significantly influenced by the predictors, indicating a primary effect of 4-HPR on retinal photoreceptor sensitivity without significant alterations of the inner nuclear layer. Thus, in contrast to previous reports at higher dose, administration of 4-HPR at 200 mg/day seems to exert subtle alterations of retinal function as measured by ERG.

Relationship between difficulty in performing daily activities and clinical measures of visual function in patients with retinitis pigmentosa.

To assess the level of perceived difficulty experienced by patients with retinitis pigmentosa (RP) in the performance of everyday activities and to determine the correlation between patients' self-reported difficulty and clinical measures of visual function. One hundred sixty-seven patients with typical RP and Usher syndrome type 2, with a wide range of disease severity, rated their difficulty in the performance of 33 activities. We obtained data on visual acuity and visual field area for all patients, and electroretinogram (ERG) recordings on a subgroup of 49 of these patients. Results from the questionnaire were analyzed with factor analysis, and patients' self-reports were compared with their clinical data using correlational analyses and multiple regression. The patients' questionnaire responses clustered into 6 factors: activities involving central vision, miscellaneous activities (no discernible common factor), activities related to mobility, driving, negotiating steps, and eating meals. Of the clinical tests, visual acuity was most strongly related to the patients' ratings of their difficulty in performance. Visual field area also was related to patients' self-assessments but not as strongly as visual acuity. Because visual field area and the ERG measures were correlated, adding ERG information did not improve predictability. In patients with RP, perceived difficulty in performing common tasks was most strongly related to level of visual acuity and visual fields. Although certain ERG amplitude measures did show positive correlations with some self-reported activities, overall, the ERG amplitude measures showed the least relationship with patients' self-reports. Our results provide insight into RP patients' perceived difficulties in performing everyday activities and the clinical measures of visual function that most highly correlate with these difficulties.

ERG measurements of the spectral sensitivity of common chimpanzee (Pan troglodytes).

The spectral sensitivity of the common chimpanzee (Pan troglodytes) was measured with electroretinogram (ERG) flicker photometry. Chromatic adaptation conditions were used to establish the presence of S-, M- and L-cone pigments. Each of 26 chimpanzees showed substantial and approximately equivalent adaptational changes over the middle and long wavelengths implying an absence of any significant polymorphic variations in the M- and L-cone pigments. As inferred from ERG measurements, the S-cone pigment of the chimpanzee has a spectral peak of about 430 nm. Chimpanzee spectral sensitivity measurements were compared to those obtained from equivalently tested normal human trichromats. The spectral sensitivity of the two species is very similar, chimpanzees being slightly more sensitive to short wavelength lights and slightly less sensitive to long wavelength lights than human subjects. Curve-fitting analyses suggest that spectral filtering may be lower in the chimpanzee lens than it is in the human lens, and that the L/M cone ratio is lower in the chimpanzee.

Age-related changes in the visual function of WBN/Kob rats--an electrophysiological study

Changes in the visual function of the male WBN/Kob rat known as diabetic strain with increasing age were studied electrophysiologically. The measurements of electroretinogram (ERG) and visual evoked potential (VEP) in male WBN/Kob rats were performed at 5, 9, 13, 17, 23, 27, 36, 45, 54, 67 and 80 weeks of age, and compared with those in male Wistar/ST rats used as control. The prolonged latencies and decreased amplitudes of a- and b- waves and oscillatory potentials of ERG in WBN/Kob rats aged over 17 or 27 weeks were recorded under the light or after 20 min dark adaptation. The visual abnormality as indicated by non-recordable ERG was obvious in WBN/Kob rats aged 67 and 80 weeks. No changes of N1, P and N2 peak latencies of VEP were recorded in WBN/Kob rats with increasing age. The amplitudes between N1 peaks and P peaks decreased remarkably in WBN/Kob rats aged 54 weeks. The amplitudes of VEP in 67 or 80 weeks old rats in which ERG disappeared showed 26 or 28% of those in 5 weeks old rats. From these results, recording of ERG and VEP suggested that the visual abnormality occurred in male WBN/Kob rats aged 67 or 80 weeks and the process of visual abnormality with increasing age was clarified.

Predicting Outcome in Central Retinal Vein Occlusion Using the Flicker Electroretinogram

To evaluate the usefulness of the 30-Hz flicker electroretinogram (ERG) in predicting outcome in patients with central retinal vein occlusion using an automated system previously developed to measure parameters of the flicker ERG and using information about the a priori probability of developing neovascularization of the iris in central retinal vein occlusion. Amplitude and timing were extracted from 30-Hz flicker ERGs of 76 patients with acute central retinal vein occlusion from a previous study. The ability of the ERG to predict the development of neovascularization of the iris based on derived parameters was measured using the area under the receiver operating characteristic curve. The predictive ability of the 30-Hz ERG amplitude, as judged by a two-alternative forced-choice procedure, was 92%. The corresponding value for implicit time was 89%. Using Bayes' theorem, we computed the probability of developing neovascularization of the iris based on a single 30-Hz flicker ERG measurement at initial patient presentation. The 30-Hz flicker ERG provides useful information about the patients with central retinal vein occlusion.

Corneal electrode for recording electroretinograms in rats.

The corneal contact lens electrode, because of its convenience, has replaced the cotton-wick electrode for recording electroretinograms from patients and animals such as dogs, rabbits, and cats. The cotton-wick electrode, however, remains popular for rat electroretinogram measurements because small contact lens corneal electrodes that fit rat eyes are difficult to fabricate. We prepared corneal electrodes from disposable needles for use in recording electroretinograms from rats. The electrodes were readily prepared, were inexpensive, and were used successfully in six rats.

Visual evoked cortical responses and electroretinograms following implantation of human fetal mesencephalon to the right caudate nucleus in Parkinson's disease

Pattern electroretinograms and visual evoked cortical responses following flash and checkerboard pattern reversal stimulation were performed in 7 patients with advanced Parkinson's disease before and after implantation of human fetal ventral mesencephalon to the head of the right caudate nucleus. Six to nine months following surgery there was bilateral enhancement of flash-evoked response amplitudes. Electroretinogram measurements were unchanged. Individual increases in amplitude and decreases in latency were seen following pattern stimulation which were not statistically significant. A relationship between change in dyskinesia, and change in checkerboard pattern stimulation amplitude at 2.4 cycles per degree suggests that amplitude effects at this stimulus frequency are mediated via altered dopaminergic receptor status in the grafted hemisphere. This may be relevent to the mechanisms leading to generalised clinical improvements following this grafting technique.

Beneficial Effect of Intravenous Taurine Infusion on Electroretinographic Disorder in Taurine Deficient Rats

We investigated the effect of intravenous taurine infusion on the electroretinogram (ERG) of taurine-deficient rats produced by treatment with guanidinoethyl sulfonate (GES), a taurine transport inhibitor. Mother rats were fed a taurine-free diet and given drinking water containing 1% GES from 2 weeks of gestation to weaning. The same feeding conditions were applied to male offspring after weaning. Both ERG measurement and continuous infusion of taurine at a dose of 10, 30 or 100 mg/animal/day were performed for 3 weeks from 7 to 10 weeks of age. GES-treatment reduced a- and b-wave amplitudes to 50% of the control levels and also increased b-wave latencies. Intravenous infusion of taurine improved these ERG abnormalities in a dose-dependent manner. Taurine concentrations in plasma, eyes and brain were also decreased by treatment with GES, and dose-dependent recovery was observed after infusion with taurine, although the concentrations of other amino acids were not affected by GES-treatment and infusion of taurine. Observations of morphological changes revealed that the retinal damage in GES-treated animals was decreased by taurine infusion. These results indicate that the changes in ERG and retinal structure observed in taurine deficiency are improved by intravenous infusion of taurine.

Correlation of Electroretinographic Findings and Peripheral Retinal Nonperfusion in Patients With Sickle Cell Retinopathy

This study examined the relationship between the proportion of peripheral retinal nonperfusion and electroretinogram measures in one untreated eye of 44 patients with sickle cell retinopathy. The proportion of peripheral retinal nonperfusion was derived from fluorescein angiographic frames covering 180 degrees of the temporal periphery. The extent of peripheral retinal capillary nonperfusion was greater in patients with peripheral retinal neovascularization compared with those without neovascularization. Reductions in electroretinogram a- and b-wave amplitudes were found in patients with and without neovascularization. However, such reductions were of greater frequency and magnitude in patients with neovascularization. Electroretinogram abnormalities were restricted to reductions in amplitude; implicit times were generally normal. In terms of the variables of the b-wave luminance-response function, abnormalities were restricted to reductions in the amplitude variable Rmax; values of logK and n were generally within the normal range. Across all patients, there was a significant negative correlation between electroretinogram amplitude measures and capillary nonperfusion, indicating that the electroretinogram provides information about the functional consequences of peripheral capillary nonperfusion in sickle cell retinopathy.

Fenretinide does not block visual pigment formation in the rat.

Abnormal retinal function has been reported in patients receiving the synthetic retinoid fenretinide. In this study, the vitamin A deprived rat was used as a model to test the possibility that fenretinide is interfering with the vitamin A transport system and/or blocking the normal uptake of 11-cis retinal into the visual pigment. Assessing retinal function by electroretinogram measurements and visual pigment formation by competition studies, our data demonstrate normal uptake of vitamin A and normal visual pigment formation in the rat after treatment with the drug.

Diurnal Changes in Structure and Function of the Compound Eye of Ligia Exotica (Crustacea, Isopoda)

ABSTRACT The ultrastructure of the retinula cells of Ligia exotica changes diurnally and in response to light/dark adaptation. At the low phase of electroretinogram (ERG) amplitude (at noon), the arrangement of microvilli is ordered and the rhabdom is of the open type. An irregular arrangement of microvilli appears at the high phase of ERG amplitude (at midnight), when the rhabdom is of the closed type. The pigment granules disperse at midnight and assemble at noon. A centrally positioned, spike-producing eccentric cell is present in each ommatidium. Spectral response curves based on ERG measurements have two maxima, one to light of 383 nm wavelength, the other at around 520 nm. These two peaks represent the two classes of receptor cells identified by intracellular recordings. The ERG responses to light of 383 nm and 520 nm wavelengths display a diurnal rhythmicity, being high at night and low during the day. However, the responses to green light are more strongly affected than those to ultraviolet light. Consequently, the eye displays a relatively higher ultraviolet-sensitivity during the day, whereas at night sensitivity to green light is increased. This behaviour, which persists in continuous darkness, suggests that an endogenous mechanism is involved in bringing about the observed diurnal morphological and physiological changes in the compound eye of Ligia exotica.

Change of synapse frequency in certain photoreceptors of the honeybee after chromatic deprivation

Bees reared under UV-light are less sensitive to long wavelength light in phototaxis experiments than are control bees. Electroretinogram measurements indicate that selective reduction in spectral sensitivity is related to smaller lamina potentials to green light. Histological investigation of synapse frequency of green sensitive photoreceptor terminals reveal a decrease in number of synapses due to the selective wavelength deprivation.

Orcadian rhythmicity of retinal photosensitivity in Japanese quail found in ERG pattern

Abstract The circadian change of the encephalic photosensitivity of quail has been demonstrated. In this study the diurnal variation of the retinal photosensitivity was investigated by the electroretinogram (ERG) to explore the phase relation between the retinal and encephalic systems. The b‐wave, a major component of the ERG, was used as a measure of retinal photosensitivity. In the bird maintained in LD12:12 the b‐wave amplitude of the ERG stayed at a high level for the first 10 h of the light period, and decreased abruptly around the time of light‐off. The decreased level continued until midnight. Thenceforth the b‐wave amplitude recovered progressively to the daytime level before the time of next light on. In the bird maintained in LD16:8, the decrease of the retinal sensitivity in the light phase was initiated prior to the time of expected light‐off, and the onset time of decreasing tendency was advanced by 2 h, with dark adaptation for 30 min given immediately before the ERG measurement. Upon contin...

Physiological and psychophysical spectral sensitivities of the cichlid fish, Hemichromis bimaculatus

AbstractElectrophysiological and psychophysical spectral sensitivities of the teleost Hemichromis bimaculatus (Pisces; Cichlidae) were determined by measurement of electroretinogram b‐wave magnitude and optomotor response threshold. The physiological and behavioral curves exhibit trivariance and trichromacy, respectively, with peaks occurring in the 460–478, 546, and 623–646 nm spectral regions. A 20‐nm shift to the red is seen in the physiological curves upon strong light adaptation, accompanied by an order of magnitude decline in overall sensitivity. Photopic physiological and behavioral sensitivities correspond in sensitivity, but differ in dominant peaks, with the red and green spectral sensitivities dominating the respective curves. The common spectral peaks correspond with suspected vertebrate photopigments, correlate with the visually oriented nuptial and parental behaviors of the cichlids, and imply cone dominance in the retina of this teleost.

Rod photoreceptors and scotopic vision in ground aquirrels.

Ground squirrel retinas contain a relatively small complement of rods (5--10% of all photoreceptors) which are thought to provide the basis for a weak scotopic visual capacity. In a previous investigation of the California ground squirrel (Spermophilus beecheyi) involving the recording of a retinal gross potential, the electroretinogram (ERG), electrophysiological evidence for a viable scotopic signal could be obtained from some, but not all of the ground squirrels examined. To further pursue the possibility that there is a structural/functional discrepancy in the relationship between rod photoreceptors and scotopic vision in the ground squirrel, several experiments involving electrophysiological, behavioral, and anatomical observations have been conducted. We found that although about one-third of the ERGs recorded from a large sample of California ground squirrels lack those characteristics which would indicate the presence of a viable scotopic signal, the retinas of all the squirrels appear to contain the same small population of rod photoreceptors. Additional experiments on the golden-mantled ground squirrel (Spermophilus lateralis), including behavioral as well as ERG measurements and anatomical observations, lead to this same conclusion.