Full-field Flash Electroretinogram Research Articles

The origins of the full-field flash electroretinogram b-wave.

The electroretinogram (ERG) measures the electrical activity of retinal neurons and glial cells in response to a light stimulus. Amongst other techniques, clinicians utilize the ERG to diagnose various eye diseases, including inherited conditions such as cone-rod dystrophy, rod-cone dystrophy, retinitis pigmentosa and Usher syndrome, and to assess overall retinal health. An ERG measures the scotopic and photopic systems separately and mainly consists of an a-wave and a b-wave. The other major components of the dark-adapted ERG response include the oscillatory potentials, c-wave, and d-wave. The dark-adapted a-wave is the initial corneal negative wave that arises from the outer segments of the rod and cone photoreceptors hyperpolarizing in response to a light stimulus. This is followed by the slower, positive, and prolonged b-wave, whose origins remain elusive. Despite a large body of work, there remains controversy around the mechanisms involved in the generation of the b-wave. Several hypotheses attribute the origins of the b-wave to bipolar or Müller glial cells or a dual contribution from both cell types. This review will discuss the current hypothesis for the cellular origins of the dark-adapted ERG, with a focus on the b-wave.

Effects of normal aging on the mouse retina assessed by full-field flash and flicker electroretinography

Changes in the full-field flash and flicker electroretinogram (ERG) that accompany normal aging were evaluated in mice. ERGs were recorded from a single cohort of C57BL/6J mice from 5 to 70 weeks of age using conventional techniques. Dark-adapted ERGs were recorded for flash luminances of − 3.0 to 1.5 log cd-s-m−2; a- and b-wave amplitude and implicit time (IT) were calculated from these responses. In addition, light-adapted flicker ERGs elicited by sinusoidally modulated light were measured for temporal frequencies of 2 to 31 Hz. Amplitudes and phases were extracted from the flicker responses using Fourier analysis. Linear quantile mixed models were used for statistical comparisons of the effects of age on amplitude and timing. There was a significant decrease in a-wave amplitude (p < 0.001) and b-wave amplitude (p < 0.001) over the 65 week study. From 5 to 70 weeks, the a- and b-wave amplitudes decreased by a factor of approximately 2. There was a small (2–14 ms), but significant (p < 0.001), delay in a- and b-wave IT over the 65 week study. There was also a significant decrease in fundamental amplitude (factor of 1.8, p < 0.001) and second harmonic amplitude (factor of 1.5, p < 0.001) over time. There were no significant age-related effects on the phase of these components (both p > 0.06). These results indicate that age scales the single flash and flicker ERG similarly, reducing response amplitude by a factor of approximately 2, from 5 to 70 weeks, with small or no effect on response timing. These data may be useful for guiding future longitudinal pre-clinical therapeutic studies.

Long-term blue light rearing does not affect in vivo retinal function in young rhesus monkeys.

Exposure to blue light is thought to be harmful to the retina. The purpose of this study was to determine the effects of long-term exposure to narrowband blue light on retinal function in rhesus monkeys. Young rhesus monkeys were reared under short-wavelength "blue" light (n = 7; 465nm, 183 ± 28lx) on a 12-h light/dark cycle starting at 26 ± 2days of age. Age-matched control monkeys were reared under broadband "white" light (n = 8; 504 ± 168lx). Light- and dark-adapted full-field flash electroretinograms (ERGs) were recorded at 330 ± 9days of age. Photopic stimuli were brief red flashes (0.044-5.68cd.s/m2) on a rod-saturating blue background and the International Society for Clinical Electrophysiology of Vision (ISCEV) standard 3.0 white flash on a 30cd/m2 white background. Monkeys were dark adapted for 20min and scotopic stimuli were ISCEV standard white flashes of 0.01, 3.0, and 10cd.s/m2. A-wave, b-wave, and photopic negative response (PhNR) amplitudes were measured. Light-adapted ERGs in young monkeys were compared to ERGs in adult monkeys reared in white light (n = 10; 4.91 ± 0.88years of age). For red flashes on a blue background, there were no significant differences in a-wave (P = 0.46), b-wave (P = 0.75), and PhNR amplitudes (P = 0.94) between white light and blue light reared monkeys for all stimulus energies. ISCEV standard light- and dark-adapted a- and b-wave amplitudes were not significantly different between groups (P > 0.05 for all). There were no significant differences in a- and b-wave implicit times between groups for all ISCEV standard stimuli (P > 0.05 for all). PhNR amplitudes of young monkeys were significantly smaller compared to adult monkeys for all stimulus energies (P < 0.05 for all). There were no significant differences in a-wave (P = 0.19) and b-wave (P = 0.17) amplitudes between young and adult white light reared monkeys. Long-term exposure to narrowband blue light did not affect photopic or scotopic ERG responses in young monkeys. Findings suggest that exposure to 12h of daily blue light for approximately 10months does not result in altered retinal function.

Inhibition of Heat Shock Protein B8 Alleviates Retinal Dysfunction and Ganglion Cells Loss Via Autophagy Suppression in Mouse Axonal Damage.

PurposeHeat shock protein B8 (HspB8) can be upregulated rapidly in many pathologic processes, but its role in traumatic optic neuropathy remains unclear. In this study, we investigated the involvement of autophagy in the effects of HspB8 by using the optic nerve crush (ONC) model.MethodsMale C57BL/6J mice were intravitreally injected with recombinant adeno-associated virus type 2 (AAV2-shHspB8 or AAV2-GFP) and subsequently received ONC by a self-closing tweezers. Western blot and immunohistochemistry staining were used to evaluate the expression of HspB8. We conducted retinal flat-mount immunofluorescence to measure the quantities of retinal ganglion cells (RGCs), and full-field flash electroretinogram (ff-ERG) and optomotor response (OMR) were used to evaluate retinal function. The autophagy level was reflected by western blot, immunohistochemistry staining, and transmission electron microscope (TEM) images. We also applied 3-methyladenine (3MA) and rapamycin (Rapa) to regulate autophagy level in optic nerve injury.ResultsONC stimulated the expression of HspB8. Declines of RGCs and ff-ERG b-wave amplitudes resulting from ONC can be alleviated by HspB8 downregulation. Increased autophagy activity after ONC was observed; however, this change can be reversed by intravitreal injection of AAV2-shHspB8. Furthermore, application of autophagy inhibitor 3MA had the same neuroprotective effects as AAV2-shHspB8, as illustrated by ff-ERG and quantities of RGCs. Also, protection of AAV2-shHspB8 was compromised by the autophagy activator Rapa.ConclusionsInhibition of HspB8 in mice optic nerve injury had neuroprotective effects, which may be derived from its downregulation of autophagy.

Use of extended protocols with nonstandard stimuli to characterize rod and cone contributions to the canine electroretinogram.

In this study, we assessed several extended electroretinographic protocols using nonstandard stimuli. Our aim was to separate and quantify the contributions of different populations of retinal cells to the overall response, both to assess normal function and characterize dogs with inherited retinal disease. We investigated three different protocols for measuring the full-field flash electroretinogram-(1) chromatic dark-adapted red and blue flashes, (2) increasing luminance blue-background, (3) flicker with fixed frequency and increasing luminance, and flicker with increasing frequency at a fixed luminance-to assess rod and cone contributions to electroretinograms recorded in phenotypically normal control dogs and dogs lacking rod function. Temporal separation of the rod- and cone-driven responses is possible in the fully dark-adapted eye using dim red flashes. A- and b-wave amplitudes decrease at different rates with increasing background luminance in control dogs. Flicker responses elicited with extended flicker protocols are well fit with mathematical models in control dogs. Dogs lacking rod function demonstrated larger amplitude dark-adapted compared to light-adapted flicker responses. Using extended protocols of the full-field electroretinogram provides additional characterization of the health and function of different populations of cells in the normal retina and enables quantifiable comparison between phenotypically normal dogs and those with retinal disease.

AAV-mediated PEX1 gene augmentation improves visual function in the PEX1-Gly844Asp mouse model for mild Zellweger spectrum disorder

Patients with Zellweger spectrum disorder (ZSD) commonly present with vision loss due to mutations in PEX genes required for peroxisome assembly and function. Here, we evaluate PEX1 retinal gene augmentation therapy in a mouse model of mild ZSD bearing the murine equivalent (PEX1-p[Gly844Asp]) of the most common human mutation. Experimental adeno-associated virus 8.cytomegalovirus.human PEX1.hemagglutinin (AAV8.CMV.HsPEX1.HA) and control AAV8.CMV.EGFP vectors were administered by subretinal injection in contralateral eyes of early (5-week-old)- or later (9-week-old)-stage retinopathy cohorts. HsPEX1.HA protein was expressed in the retina with no gross histologic side effects. Peroxisomal metabolic functions, assessed by retinal C26:0 lysophosphatidylcholine (lyso-PC) levels, were partially normalized after therapeutic vector treatment. Full-field flash electroretinogram (ffERG) analyses at 8 weeks post-injection showed a 2-fold improved retinal response in the therapeutic relative to control vector-injected eyes. ffERG improved by 1.6- to 2.5-fold in the therapeutic vector-injected eyes when each cohort reached 25 weeks of age. At 32 weeks of age, the average ffERG response was double in the therapeutic relative to control vector-injected eyes in both cohorts. Optomotor reflex analyses trended toward improvement. These proof-of-concept studies represent the first application of gene augmentation therapy to treat peroxisome biogenesis disorders and support the potential for retinal gene delivery to improve vision in these patients.

Correlations Between Dark-Adapted Rod Threshold Elevations and ERG Response Deficits in Duchenne Muscular Dystrophy.

PurposeThe purpose of this study was to characterize changes in the full-field flash electroretinogram (ERG) in association with psychophysical dark-adapted visual thresholds in patients with genetically characterized Duchenne muscular dystrophy (DMD) either lacking Dp427 (Up 30) or at least Dp260 in addition to Dp427 (Down 30).MethodsTwenty-one patients with DMD and 27 age-similar controls participated in this study. Dark-adapted (0.01, 3.0, and 10 cd.s/m² flashes) and light-adapted (3.0 cd.s/m² flash) ERGs were recorded following International Society for Clinical Electrophysiology of Vision (ISCEV) standard protocols. Visual detection thresholds to 625-nm (cone function) and 527-nm (rod function) light-emitting diode (LED) flashes (2 degree diameter) were measured during a dark adaptation period after a 1-minute exposure to a bleaching light (3000 cd/m²). Initially, 8 minutes of interleaved 625-nm and 527-nm thresholds were measured. After an additional 5 minutes of dark-adaptation, a second set of threshold measurements to 527-nm stimuli was performed during the subsequent 6 minutes.ResultsDark-adapted b-wave amplitude was significantly reduced to all strengths of flash and a-wave in response to the strong flash stimulus was delayed (15.6 vs. 14.7 ms, P < 0.05) in patients with Down 30 compared with controls. Dark-adapted cone thresholds did not differ among the groups (−2.0, −1.8, and −1.7 log cd/m² for Down 30, Up 30, and controls, respectively, P = 0.21). In contrast, dark-adapted rod thresholds were elevated (F(2,36) = 8.537, P = 0.001) in patients with Down 30 (mean = −3.2 ± 1.1 log cd/m²) relative to controls (mean = −4.2 ± 0.3 log cd/m²). Dark-adapted b-wave amplitudes were correlated with dark-adapted rod sensitivity in patients with DMD (Spearman Rho = 0.943, P = 0.005). The changes were much smaller or absent in patients with intact Dp260.ConclusionsDp260 is particularly required for normal rod-system function in dark adaptation.

Organic visual loss measured by kinetic perimetry and retinal electrophysiology in children with functional amblyopia.

To demonstrate an organic (retinal) amblyogenic defect in functional amblyopes not responding to treatment. Twenty-four children (Mean age: 5.9 ± 1.8years; range: 4-10years) with functional amblyopia were recruited for this study. All these children underwent complete ophthalmic and orthoptic evaluation. In addition, Kinetic Goldman Visual Fields (KGVF), Spectral Domain Optical Coherence Tomography (SD-OCT), full field flash electroretinograms (ffERG) and multifocal electroretinograms (mfERG) were also performed. Ratios were subsequently derived by comparing the amplitudes obtained from the amblyopic eye (AE) to the good eye (GE) for the a- and b-waves of the ffERG, as well as for the ring analysis of the mfERG. KGVF showed a central scotoma of varying size (3°-7°) and density (absolute to relative), with increasing target size in 14/24 patients whose best post-treatment vision in the AE ranged from 20/100 to 20/40. The scotoma decreased in size and density with improving vision until a plateau of recovery was reached. The remaining 10/24 patients with a vision ≥ 20/30 showed no scotoma. SD-OCT showed no significant difference between the AE and GE. ffERG and mfERG were obtained in 18/24 patients. The ffERG AE/GE ratio was abnormal in 7 patients, 5 of which had large scotomas on KGVF. The mfERG ring 1 AE/GE ratio was significantly (p < .05) attenuated in 9/18 patients out of which 3 were no longer amblyopic. However, there was no significant difference (p > .05) in ring 1 AE/GE amplitude ratio between those who achieved 20/50-20/40 (.81 ± .26) and those with ≥ 20/25(.86 ± .25). The combined findings of central scotoma on KGVF and mfERG anomalies in patients who did not achieve optimal vision with treatment suggest an underlying organic defect impairing macular function.

Retinal ganglion cell ablation in guinea pigs

Guinea pigs are a common model of human ocular conditions; however, their visual function has not been fully characterized. The purpose of this study was to determine the contributions of retinal ganglion cells to structural and functional measures in guinea pigs. Healthy adult guinea pigs (n = 12) underwent unilateral optic nerve crush. Retinal structure was assessed with spectral domain optical coherence tomography (OCT), and thickness of the ganglion cell/nerve fiber layer (GC/NFL) was determined. Visual function was assessed with optomotor tracking of a drifting grating and light adapted electroretinograms (ERGs). From flash ERGs, a-wave, b-wave, oscillatory potentials (OPs), and photopic negative response (PhNR) were analyzed. From pattern ERGs, N1P1 and P1N2 were analyzed. Histological studies were done at various time points for ganglion cell quantification. Optomotor tracking was absent in optic nerve crush eyes following optic nerve crush. Significant thinning of the GC/NFL was evident four weeks following the crush. Flash ERGs revealed a significant reduction in the OP1 amplitude two weeks following crush (P < 0.01) and in the PhNR amplitude six weeks following crush (P < 0.01). There were no significant changes in a-wave, b-wave, or pattern ERG responses (P > 0.05 for all). In vivo OCT imaging showed progressive thinning of inner retinal layers. Ganglion cell density, quantified histologically, was significantly reduced by 75% in the optic nerve crush eye compared to the control eye at four weeks following crush. These findings indicate that retinal ganglion cells contribute to the PhNR and OP1 components of the full field flash ERG, but not significantly to the pattern ERG in guinea pigs. This study demonstrates that OCT imaging and full field flash ERGs are valuable in assessing retinal ganglion cell loss in vivo in guinea pigs and will help to further establish the guinea pig as a model of human ocular pathologies.

Beneficial effects of vincamine with thioctic acid and lutein on retinal and optic nerve functions in an opaque media.

To detect whether the combination of vincamine, thioctic acid and lutein will improve the retina and optic nerve functions in cases of an opaque media with an optic nerve and/or a retinal defect or not. Totally 2000 patients (2000 eyes) of corneal opacities with defects in the optic nerve or/and the retinal functions were studied. Every patient received three types of drugs: thioctic acid with cyanocobalamine, vincamine, and lutein. The drugs were given daily for 3-12mo according to patient's responses. Full field flash electroretinogram (ERG) and flash visual evoked potential (VEP) were done before treatment and at 1, 3, 6, and 12mo sequentially. Patients were followed up for 12mo. In the 2000 eyes, 1000 eyes had both moderate optic nerve and retinal function defects; and 840 eyes out of the 1000 improved with the medical treatment. Another 500 eyes out of the 2000 eyes had extinguished retinal function with normal optic nerve function and only 125 eyes of them improved. The 290 out of the 2000 eyes had severe defects in optic nerve with normal retinal function and 130 of them improved. Another 210 eyes have mild optic nerve and retinal function defects and 194 improved. The combination of vincamine, thioctic acid with cyanocobalamine, and lutein improved both retina and optic nerve functions mainly in mild and moderate defect than in severe cases.

Retinal damage after exposure to white light emitting diode lights at different intensities in Sprague-Dawley rats

Background: The usage of the light emitting diode (LED) has been increasingly applied in the illumination setting and electronic equipment. However, the effect of LED lights on the retina remains unclear. In this study, we observed and analyzed the impact of white LED lights at different intensities on the function and morphology of rat retinas. Methods: Thirty-six Sprague-Dawley rats weighing 150–180 g were randomly divided into six groups (n=6 in each group) including a normal control (NC) group, 4 white LED groups at different light intensities (4,000, 6,000, 7,000, and 10,000 lux), and an ultraviolet B (UVB) lighting group (302 nm, 1,000 µw/cm 2 ). After 24 hours of continuous illumination, full-field flash electroretinogram (FERG) and pathological examination were performed in each group. Results: As revealed by FERG, the impairment of retinal function gradually worsened with the increase of LED light intensity. In contrast, the UVB group had the most severe retinal function impairment. Particularly, the functional damage of rod cells and inner nuclear layer cells was the main FERG finding in each group. In the NC group, the retina had typical morphologies featured by well-defined structures, clearly visible border between the inner and outer segments, and neatly arranged inner and outer nuclear layer cells. After 24 hours of illumination, the inner and outer parts of the retina in the 4,000 lux group were still neatly arranged, along with a clear border; however, the inner and outer nuclear layers were randomly arranged, and some irregular nuclei and cells were lost. The damage of the internal and external retinal segments and the internal and external nuclear layers became more evident in the 6,000 lux group, 7,000 lux group, and 10,000 lux group. The UVB group had a more obviously disordered arrangement of inner and outer nuclear layers and loss of cells. Conclusions: Continuous exposure to white LED light can cause structural and functional damage to rat retinas, and such damage is related to the intensity of illumination. Therefore, the risk of retinal damage should be considered during LED illumination, and proper LED illumination intensity may help to maintain eye health.

The neuro-ophthalmological effects related to long-term occupational exposure to organic solvents in painters.

Organic solvents are widely used in many industries, and usually, exposure occurs with mixtures of solvents. Organic solvent mixtures are known for their ability to affect tissues of high lipid content including the myelin sheath in the nervous system. The purpose of this work was to study the evidence that long-term (more than 10 years) exposure to organic solvent mixtures among painters can induce neuro-ophthalmological effects on the function of retinal ganglion cells and the optic tract. Twenty workers with long-term occupational exposure to mixed organic solvents were compared to 40 control subjects. The controls were matched for age, gender, and demographic characteristics but were not occupationally exposed to any known organic solvents, using the following comparators: visual evoked potential (VEP), electroretinogram (ERG), color vision (CV), and contrast sensitivity (CS) testing. Environmental monitoring was done in the work environment with consideration to the American Conference of Governmental Industrial Hygienists Threshold Limit Values (ACGIH-TLVs). The exposed group had significantly longer latency and higher amplitude of VEP waves especially P100, higher Color Confusion Index (CCI), especially affecting the blue-yellow spectrum, and lower Log CS. There was no significant difference between exposed and nonexposed groups in full-field flash ERG response; however, in the pattern ERG, the exposed group had significantly longer latency of P50, which reflects changes in the retinal ganglion cell. Long-term occupational exposure to mixed organic solvents appeared to affect the optic tract functions in the form of increasing latency of VEP response, affecting the quality of CV and decreasing CS. It also affects the retinal ganglion cell layer with increased latency of P50 of the pattern ERG response.

The characteristics of the full-field flash electroretinogram in rats with oxygen induced retinopathy

Objective To observe the characteristics of the full-field flash electroretinogram (F-ERG) in rats with oxygen induced retinopathy (OIR). Methods Twenty-four neonatal Sprague Dawley rats were divided into OIR group and control group. In OIR group, 12 rats were exposed to (75±2)% oxygen for 7 days and then to room air for 7 days; in control group, 12 rats were raised in room air for 14 days. At postnatal day 21, F-ERG tests were performed to examine the rod response , the maximum mixing reaction and the cone reaction. Results Compared with the control group, the b-wave amplitudes decreased (t=3.650) and the implicit times increased (t=2.410) in rod response in OIR group, the differences were statistically significant (P 0.05). 0.001 cd.s/m2 light intensity stimulation on rats F-ERG wave almost no response. 0.010 cd.s/m2 light intensity stimulation on rats can be recorded to the rod response waveform, with the increase of light intensity, the amplitude of b-wave increases. Conclusions F-ERG of OIR rat showed that the amplitude and sensitivity of the rod response and maximal rod-cone response was decreased. The intensity of light had effect on the OIR rod cells, and the amplitude of b-wave increased with the increase of light intensity. Key words: Retinal diseases/physiopathology; Electroretinography; Animal experimentation

Transcorneal electrical stimulation prevents secondary retinal ganglion cell death after acute ocular hypertensive injury through modulation of microglia‐mediated local inflammatory response

PurposeTo investigate neuroprotective effect of transcorneal electrical stimulation (TcES) on retinal ganglion cells (RGC) after acute ocular hypertension related retinal injury in gerbils.MethodsThe right eye of each gerbil was used for experiments. Acue ocular hypertensive injury was induced via intracameral infusion of basic salt solution. Intraocular pressure (IOP) was adjusted by changing the bottle height position. For all gerbis, right eye IOP was elevated to 85 mmHg for 1 h. In the treatment group, TcES was applied to the surgical eye immediately and then twice weekly for a total of 1 month. In the control group, sham TcES was given to the surgical eye during the same time points. Retinal function was assessed and compared between groups using a full field flash electroretinogram and a light/dark transition box test. For histological analysis, the number of RGCs, astrocytes and microglial cells were counted by immunofluorescence staining after the gerbils were sacrificed on day 7 and day 28. Real time PCR and western blot analysis were conducted to compare expression of IL‐10, IL‐6, Cox‐2, TNF‐α and NFκB phorsphorylation between groups.ResultsTcES treated eyes had significantly higher RGC survival at 1 month compared to controls. This was associated with improved RGC function and vision‐related behaviour. Furthermore TcES treated eyes were shown to have increased IL‐10 expression, with a corresponding reduction in IL‐6 and COX‐2 expression as well as reduction in NF‐kB phosphorylation. This was associated with a suppression in microglial cell activation in TcES treated eyes.ConclusionsEarly treatment with TcES in gerbils protected the RGCs from damage and preserved retinal function in acute ocular hypertensive injury through modulation of the microglial‐cell activated local inflammatory response.

The tests

SummaryVisual electrophysiology tests provide objective information about visual pathway function. They characterise ‘bio‐electrical’ changes in the retina and visual pathway to the striate cortex. The International Society for Clinical Visual Electrophysiology of Vision, [ISCEV], publishes standards and guidance for performing each test; download from www.ISCEV.com. There are five. The electro‐oculogram, EOG, indicates RPE physiology. A full field flash electroretinogram, ffERG, summates activity from the whole retina and distinguishes photoreceptor and inner retinal function. The pattern ERG, PERG, is a localised retina response produced by an alternating black and white checkerboard. The PERG has two components which may be used to measure macular function and retinal ganglion cell function. Multifocal patterns stimulate even smaller localised regions of retina and the resulting mfERG may depict the geographic extent of macular or cone dysfunction. The visual evoked potential, VEP, reflects changes in the striate cortex produced by flashes or patterns and distinguishes optic nerve, chiasmal and post chiasmal pathway function. This talk will describe the patient's perspective, what the results look like and how they are analysed.

Objective Determination of Retinal Function in Bietti Crystalline Retinopathy.

A 44-year-old female patient without any known systemic or ocular disease presented with progressive visual loss and night vision disturbance. Visual acuity was 0.6 in the right eye and 0.2 in the left eye. Tiny, yellow crystalline deposits were seen on fundus examination. In addition, areas of retinal pigment epithelium and choriocapillaris atrophy were detected. Rod and cone responses were depressed in full-field flash electroretinogram. Multifocal electroretinogram testing showed severe foveal function disturbance with less severe but still depressed responses toward the periphery. Multiple hyperreflective lesions were detected in the retina in optical coherence tomography. We aimed to present the role of ocular electrophysiology by comparing the patient’s signs and symptoms with her ocular electrophysiological test results.

Retinal cross talk in the mammalian visual system.

The existence and functional relevance of efferent optic nerve fibers in mammals have long been debated. While anatomical evidence for cortico-retinal and retino-retinal projections is substantial, physiological evidence is lacking, as efferent fibers are few in number and are severed in studies of excised retinal tissue. Here we show that interocular connections contribute to retinal bioelectrical activity in adult mammals. Full-field flash electroretinograms (ERGs) were recorded from one or both eyes of Brown-Norway rats under dark-adapted (n = 16) and light-adapted (n = 11) conditions. Flashes were confined to each eye by an opaque tube that blocked stray light. Monocular flashes evoked a small (5-15 μV) signal in the nonilluminated eye, which was named "crossed ERG" (xERG). The xERG began under dark-adapted conditions with a positive (xP1) wave that peaked at 70-90 ms and ended with slower negative (xN1) and positive (xP2) waves from 200 to 400 ms. xN1 was absent under light-adapted conditions. Injection of tetrodotoxin in either eye (n = 15) eliminated the xERG. Intraocular pressure elevation of the illuminated eye (n = 6) had the same effect. The treatments also altered the ERG b-wave in both eyes, and the alterations correlated with xERG disappearance. Optic nerve stimulation (n = 3) elicited a biphasic compound action potential in the nonstimulated nerve with 10- to 13-ms latency, implying that the xERG comes from slow-conducting (W type) fibers. Monocular dye application (n = 7) confirmed the presence of retino-retinal ganglion cells in adult rats. We conclude that mammalian eyes communicate directly with each other via a handful of optic nerve fibers. The cross talk alters retinal activity in rats, and perhaps other animals.

Coexistence of Posterior Staphyloma, Retinitis Pigmentosa and Moderate Myopia.

The authors report a 22-year patient presented with night-blindness and progressive visual loss. Ophthalmologic examination included slit lamp biomicroscopy, best-corrected distance visual acuity, cycloplegic refraction, A-mode and B-mode ultrasonography, and full-field flash electroretinogram (ERG). Cycloplegic refractions were -6.00 (-1.25 x 175) dpt in the right eye and -7.00 (-1.50 x 165) dpt in the left eye. Slit lamp examination showed normal anterior segment. Fundoscopic examination revealed bone-spicule pigmentations, waxy optic disc, arteriolar narrowing and posterior staphyloma, with 5 optic disc in diameter in the right eye and 4 optic disc diameter in the left. Ocular ultrasonography confirmed staphyloma. Full-field ERG showed evidence of a generalized retinal dysfunction involving both rod and cone responses, supported the diagnosis of retinitis pigmentosa.

In vivo electroretinographic studies of the role of GABAC receptors in retinal signal processing

All three classes of receptors for the inhibitory neurotransmitter GABA (GABAR) are expressed in the retina. This study investigated roles of GABAR, especially GABACR (GABA(A)-ρ), in retinal signaling in vivo by studying effects on the mouse electroretinogram (ERG) of genetic deletion of GABACR versus pharmacological blockade using receptor antagonists. Brief full-field flash ERGs were recorded from anesthetized GABACR−/− mice, and WT C57BL/6 (B6) mice, before and after intravitreal injection of GABACR antagonists, TPMPA, 3-APMPA, or the more recently developed 2-AEMP; GABAAR antagonist, SR95531; GABABR antagonist, CGP, and agonist, baclofen. Intravitreal injections of TPMPA and SR95531 were also made in Brown Norway rats. The effect of 2-AEMP on GABA-induced current was tested directly in isolated rat rod bipolar cells, and 2-AEMP was found to preferentially block GABACR in those cells. Maximum amplitudes of dark (DA) and light-adapted (LA) ERG b-waves were reduced in GABACR−/− mice, compared to B6 mice, by 30–60%; a-waves were unaltered and oscillatory potential amplitudes were increased. In B6 mice, after injection of TPMPA (also in rats), 3-APMPA or 2-AEMP, ERGs became similar to ERGs of GABACR−/− mice. Blockade of GABAARs and GABABRs, or agonism of GABABRs did not alter B6 DA b-wave amplitude. The negative scotopic threshold response (nSTR) was slightly less sensitive in GABACR−/− than in B6 mice, and unaltered by 2-AEMP. However, amplitudes of nSTR and photopic negative response (PhNR), both of which originate from inner retina, were enhanced by TPMPA and 3-APMPA, each of which has GABAB agonist properties, and further increased by baclofen. The finding that genetic deletion of GABACR, the GABACR antagonist 2-AEMP, and other antagonists all reduced ERG b-wave amplitude, supports a role for GABACR in determining the maximum response amplitude of bipolar cells contributing to the b-wave. GABACR antagonists differed in their effects on nSTR and PhNR; antagonists with GABAB agonist properties enhanced light-driven responses whereas 2-AEMP did not.

Ocular and neurodevelopmental features of Duchenne muscular dystrophy: a signature of dystrophin function in the central nervous system.

Multiple isoforms of dystrophin (Dp427, Dp260, Dp140, Dp71) are expressed differentially in the central nervous system (CNS) including the retinal layers. Disruption of these protein products is responsible for cognitive dysfunction, electroretinogram (ERG) abnormalities and behavioural disorders in Duchenne muscular dystrophy (DMD). We studied the ocular characteristics and neuropsychiatric profile of 16 DMD boys. The ISCEV standard, full-field flash ERGs were assessed. Intellectual ability and behavioural disturbances were measured. All genotypes were associated with mildly abnormal photopic ERG a:b-wave amplitude ratios. In addition, we identified the following genotype/phenotype correlations: boys with mutations upstream of exon 30 (ie, isolated Dp427 altered expression) showed normal scotopic a:b ratios, abnormal photopic oscillatory potential OP2 and normal scotopic OP2. Conversely, all boys with DMD mutations downstream of exon 30 showed profoundly 'negative' scotopic ERGs (a:b ratios >1). In these patients, the involvement of Dp260 isoform resulted in the absence of slow rod pathway signalling in15 Hz scotopic flicker ERGs. These boys had abnormal scotopic OP2 and normal photopic OP2. Finally, children with mutations also affecting Dp71 were associated with more pronounced electronegative ERGs. When correlating ERGs to neurodevelopmental outcome, we found a positive correlation between negative scotopic ERGs and neurodevelopmental disturbances, and the most severe findings were in boys with Dp71 disruption. These findings suggest a strong association between DMD mutations affecting different DMD isoforms with characteristically abnormal scotopic ERGs and severe neurodevelopmental problems. The role of the ERG as a potential biomarker for dystrophin function in the CNS and response to novel genetic therapies warrants further exploration.