The photopic negative response of the flash electroretinogram in retinal vein occlusion

The photopic negative response (PhNR) has recently been shown to be severely affected in central retinal artery occlusion (CRAO), despite relative preservation of the cone b-wave compared to that in the healthy unaffected fellow eye. The aim of this study was to test how the PhNR of the flash electroretinogram (ERG) is affected in human retinal vein occlusion. PhNR was elicited with red stimuli (1 cd s/m², 5 cd s/m², and 7 cd s/m² with 4 ms duration) and blue background (10 cd/m²). Standard Ganzfeld flash ERG was produced according to the ISCEV standard for the clinical electroretinogram (2004). Sixteen patients with central retinal vein occlusion (CRVO), 14 patients with branch retinal vein occlusion (BRVO), and 16 controls were analyzed. The amplitude of the PhNRs was significantly smaller in the CRVO and BRVO eyes than those in the unaffected fellow or control eyes (p = 0.000). There was a significantly greater reduction of PhNR amplitudes than that of other waves including the OPs, rod b-wave, combined a-wave and b-wave, cone a-wave and b-wave, and 30 Hz flicker ERG. Thus, PhNR amplitude in retinal vein occlusion is severely affected. There is a potential role for PhNR in assessing inner retinal damage and evaluating the effect of treatment.     

Inter-ocular and inter-session reliability of the electroretinogram photopic negative response (PhNR) in non-human primates

PURPOSE: To assess the inter-ocular and inter-session reliability for a range of parameters derived from the photopic electroretinogram (ERG) in a group of normal non-human primates. METHODS: Inter-ocular differences for photopic ERGs were assessed in a group of normal anesthetized adult rhesus monkeys (Macaca mulatta, n=29); inter-session reliability was assessed for 23 eyes of 23 animals tested 3 months later. Signals were acquired using Burian-Allen contact lens electrodes, whereby the contralateral cornea served as a reference. Photopic ERGs were elicited using red Ganzfeld flashes (-0.5-0.67 log photopic cd.sm(-2)) on a rod suppressing blue-background (30 scotopic cdm(-2)). Measurement reliability was established for a-wave, b-wave, photopic negative response (PhNR) and oscillatory potential (OP) amplitudes, as well as for their implicit times, by calculation of the 95% limits-of-agreement (LOA) and the coefficient-of-variation (COV) for each parameter. RESULTS: OP and a-wave amplitudes increased with intensity up to 0.67 log photopic cd.sm(-2), following a typical saturating function, whereas b-wave and PhNR amplitudes both declined above 0.42 log photopic cd.sm(-2). Inter-session variability was greater than inter-ocular variability. The inter-session COVs for PhNR amplitude (10-20%) were similar to the other photopic ERG components (a-wave: 12-17%, b-wave: 12-17%, OPs: 13-19%). Inter-session LOAs were also similar across components, but on average, were smallest for responses to moderate intensities (0.0-0.42 log photopic cd.sm(-2)). CONCLUSION: In non-human primates, the 95% LOA for inter-session measurements of the photopic ERG a-wave, b-wave, OPs and PhNR are all similar. Inner-retinal damage may best be measured using the PhNR amplitude for moderately bright stimulus intensities. B-wave and PhNR amplitudes for brighter flashes are smaller and more variable. The ratio of PhNR:b-wave amplitudes manifests smaller variability and may therefore be useful for detection of selective PhNR loss.     

Changes in retinal thickness are correlated with alterations of electroretinogram in eyes with central retinal artery occlusion

BACKGROUND: We investigated the relationship between the retinal thickness and electroretinogram (ERG) components in patients with central retinal artery occlusion (CRAO). METHODS: The optical coherence tomographic (OCT) images and ERGs of the nine patients (six men and three women; mean age, 61.8 years) were retrospectively analyzed. The thickness of the inner and outer retinal layers at 1 and 2 mm nasal and temporal to the fovea was measured in the horizontally scanned OCT images. The ratio of the inner layer thickness/sensory retinal thickness (IT/ST ratio) was calculated. The amplitudes of the a- and b-waves of the mixed rod-cone ERGs and the photopic negative response (PhNR) of the photopic ERGs were analyzed. The ratio of the amplitude of each component in the affected eye to that of the healthy fellow eye (a/f ratio) was calculated. RESULTS: In the chronic phase (1 to 8 months after onset, eight eyes), the inner layer was significantly thinner than that in the acute phase (P = 0.0147, 0.0076, 0.002, and 0.0003 for 2 mm nasal, 1 mm nasal, 1 mm temporal, and 2 mm temporal respectively, within 5 days of onset, six eyes), while the thickness of outer layer was not significantly changed. The ERGs were recorded 6.4 +/- 1.5 days after the onset of CRAO. The median of the a/f ratio was 0.84 in the a-wave, 0.56 in the b-wave, and 0.27 in the PhNR. The IT/ST in the chronic phase was positively correlated with the a/f ratio of the amplitude of the PhNR. CONCLUSIONS: Measurement of retinal thickness by OCT can be useful for monitoring the changes following CRAO. The correlation between the retinal thickness, especially inner layer thickness, and the ERG components was determined, suggesting that the PhNR in the acute phase might be a good indicator for predicting the thinning of the damaged retina in the chronic phase.     

Comparison of electroretinographic responses between two different age groups of adult Dark Agouti rats

AIM: To describe and compare the differences in electroretinographic responses between two different age groups of adult Dark Agouti (DA) rats and to better understand the effect of age on retinal histology and function.METHODS: The electroretinographic responses of two different age groups of adult DA rats were compared. Animals were divided into younger adult DA rats 10-12wk (n=8) and older adult DA rats 17-19wk (n=8). Full field electroretinography (ERG) was recorded simultaneously from both eyes after dark adaption and light adaption and parameters including the positive scotopic threshold response (pSTR), negative scotopic threshold response (nSTR), scotopic a-wave, b-wave, photopic a-wave, b-wave and photopic negative response (PhNR) were compared between groups.RESULTS: The older adult rats displayed lower stimulation thresholds of the STRs (pSTR and nSTR) and higher amplitudes of pSTR, scotopic a-wave and b-wave, photopic b-wave and PhNR amplitudes, with shorter implicit times. Photopic a-wave amplitudes were however higher in the younger adult rats.CONCLUSION:In summary, for the rod system, photoreceptor, bipolar cell and RGC activity was enhanced in the older adult rats. For the cone system, RGC and bipolar cell activity was enhanced, while photoreceptor activity was depressed in the older adult rats. Such age-related selective modification of retinal cell function needs to be considered when conducting ophthalmic research in adult rats.     

Origin of electroretinogram amplitude growth during light adaptation in pigmented rats

We assessed the growth of the rat photopic electroretinogram (ERG) during light adaptation and the mechanisms underlying this process. Full field ERG responses were recorded from anesthetized adult Brown-Norway rats at each minute for 20 min of light adaptation (backgrounds: 1.8, 2.1, 2.4 log scotopic cd m(-2)). The rat photopic b-wave amplitude increased with duration of light adaptation and its width at 33% maximal amplitude narrowed (by approximately 40 ms). These effects peaked 12-15 min after background onset. The narrowing of the b-wave reflected steepening of the b-wave recovery phase, with little change in the rising phase. OP amplitudes grew in proportion to the b-wave. Inhibition of inner retinal responses using TTX resulted in a greater relative growth of b-wave and OP amplitude compared with fellow control eyes, and delayed the change in recovery phase by approximately 5 min. Inhibition of all ionotropic glutamate receptors with CNQX/D-AP7 delayed both rising and recovery phases equally (approximately 12 ms) without altering b-wave width or the time course of adaptation changes. These outcomes suggest that inner retinal light responses are not directly responsible for b-wave amplitude growth, but may contribute to the change in its recovery phase during adaptation. A TTX-sensitive mechanism may help to hasten this process. The cone a-wave was isolated using PDA/L-AP4 or CNQX/L-AP4. A-wave amplitude (35 ms after stimulus onset) also increased with time during light adaptation and reached a maximum (130 +/- 29% above baseline) 12-15 min after background onset. B-wave amplitude growth in fellow control eyes closely followed the course and relative magnitude of cone a-wave amplitude growth. Hence, the increase of the cone response during light adaptation is sufficient to explain b-wave amplitude growth.     

Photopic ERGs in patients with optic neuropathies: comparison with primate ERGs after pharmacologic blockade of inner retina

PURPOSE: To determine whether anterior ischemic optic neuropathy and compressive optic neuropathy in humans alter the photopic flash ERG and to investigate the cellular origins of the waves that are affected by pharmacologic agents in primates. METHODS: Photopic flash ERGs were recorded differentially, with DTL electrodes, between the two eyes of 22 patients with diagnosed optic neuropathy (n = 17, anterior ischemic optic neuropathy [AION]; n = 5, compressive optic neuropathy) and 25 age-matched control subjects and in 17 eyes of 13 monkeys (Macaca mulatta). The stimulus consisted of brief (<5 ms) red (lambda(max) = 660 nm) Ganzfeld flashes (energy range, 0.5-2.0 log td-s) delivered on a rod-saturating blue background of 3.7 log sc td (lambda(max) = 460 nm). An eye of the patient with ischemic changes at the disc was classified as symptomatic if it showed visual field defects with a mean deviation (MD) of P < 2%. Recordings in macaque monkeys were made before and after inner retinal blockade with tetrodotoxin (TTX) (1.2-2.1 microM; n = 7), TTX+N-methyl-d-aspartate (NMDA; 1.4-6.4 mM; n = 7), and cis-2, 3 piperidine dicarboxylic acid (PDA; 3.3-3.8 mM; n = 3). RESULTS: The PhNR amplitude was significantly reduced in both symptomatic (P = 3.4 x 10(-8)) and asymptomatic (P = 0.036) eyes of patients with AION or compressive optic neuropathy (P = 0.0054) compared with control subjects. The PhNR amplitude in the symptomatic eye showed a moderate correlation with field defects (P < 0.05) similar to previous findings in open-angle glaucoma. The a-wave also was reduced significantly in the symptomatic eye (P = 0.0002) of patients with AION. The i-wave, a positive wave on the trailing edge of the b-wave peaking around 50 ms, became more prominent in eyes in which the PhNR was significantly reduced. In monkeys, the PhNR was eliminated by TTX. The a-wave at the peak and later times was reduced by TTX, further reduced by NMDA, and eliminated after PDA in response to the red stimuli. PDA also eliminated the i-wave. CONCLUSIONS: PhNR amplitude is significantly reduced in eyes with open-angle glaucoma, AION, and compressive optic neuropathy. Experiments in primates indicate that this reduction reflects loss of a spike-driven contribution to the photopic ERG. There also are small spike-driven contributions to the a-wave elicited by full-field red stimuli. The i-wave, which becomes more prominent when the PhNR is reduced, has origins in the off-pathway distal to the ganglion cells.     

Correlation between photopic negative response and retinal nerve fiber layer thickness and optic disc topography in glaucomatous eyes

PURPOSE: To investigate whether there is a significant correlation between the photopic negative response (PhNR) of the electroretinogram (ERG) and retinal nerve fiber layer thickness and optic disc topography in glaucomatous eyes. METHODS: Ninety-nine eyes of 53 patients with open-angle glaucoma (OAG) and 30 eyes of 28 normal volunteers were studied. Photopic ERGs were elicited by red stimuli (644 nm, 1600 cd/m(2)) on a blue background (470 nm, 40 cd/m(2)). The mean deviation (MD) of the visual field was obtained by static visual field analyses. The topography of the optic nerve head was determined by confocal scanning laser ophthalmoscopy. The retinal nerve fiber layer thickness (RNFLT) around the optic nerve head was measured with a scanning laser polarimeter. RESULTS: The amplitude of the PhNR and the PhNR/b-wave ratio decreased with an increase in visual field defects. The logarithmic values of the PhNR amplitude and PhNR/b-wave amplitude ratio were significantly correlated with the MD better than the linear values. The PhNR amplitude and PhNR/b-wave amplitude ratio were significantly correlated with the RNFLT and the rim area of the optic disc and with the cup/disc area ratio. These correlations were higher when expressed linearly than when stated logarithmically. The sensitivity and specificity were 77% and 90% for the PhNR amplitude and 70% and 87% for the PhNR/b-wave amplitude ratio when the optimal cutoff values were used. Although the a-wave amplitude correlated with the MD, the a-wave amplitudes of most of the patients fell within the normal range. The correlation between the b-wave amplitude and MD was not significant. CONCLUSIONS: The PhNR amplitudes correlate with the decrease in function and morphology of retinal neurons in eyes with OAG. The linear relationship between the PhNR and the structural parameters indicates that inner retinal function declines proportionately with neural loss in eyes with glaucoma.     

Unilateral electronegative ERG of non-vascular aetiology

BACKGROUND: Full field and pattern electroretinograms (ERG, PERG) are performed to assess generalised retinal function and macular function, respectively. An (electro) negative full field ERG usually describes an ISCEV standard maximal response in which the b-wave is smaller than a normal or minimally reduced a-wave and indicates dysfunction that is post-phototransduction. The most common cause of a unilateral negative ERG is central retinal artery occlusion (CRAO) or birdshot chorioretinopathy (BCR). This study examines the clinical and electrophysiological features of patients with unilateral negative ERG who do not have CRAO or BCR. METHODS: 12 patients were ascertained with a unilateral negative ERG in whom a vascular aetiology and BCR were excluded. Most presented with symptoms of central retinal dysfunction. In 11 of the 12 patients additional long duration photopic stimuli were used to test cone system ON and OFF responses. RESULTS: All 12 patients had unilateral electronegative bright flash full field ERGs indicating total or relative preservation of rod photoreceptor function, but dysfunction post-phototransduction. Seven of these patients had non-specific inflammatory changes in the eye with the negative ERG. Six patients, including five with inflammatory signs, had involvement of the cone ON response with complete preservation of cone OFF responses. A further three patients showed evidence of cone ON response abnormality with less severe OFF response involvement. CONCLUSION: The ERGs in this heterogeneous group of patients predominantly showed post-phototransduction involvement of the ON pathways. Sparing of the cone OFF response was often observed. The majority of patients had signs of previous inflammation and it is speculated that these highly unusual unilateral changes may be mediated via an autoimmune mechanism.     

电生理测试作为早期青光眼诊断指标的横断面研究

明视负向反应(PhNR)和图形视网膜电图(PERG)的结果作为评估青光眼的诊断指标.10例对照组和15例早期青光眼患者接受了完整的眼科检查,包括视力测量,眼压(IOP)测量,眼底检查和视野检查.同时进行图形视网膜电图和全视野视网膜点图纪录.青光眼组的平均偏差和图形平均标准偏差显著较低(P＜0.001,P＜0.01).PERGN95,PhNR,b波以及PhNR/b波的幅值显著较低(P＜0.001).眼压升高降低了PERG与PhNR的振幅.     

Comparison on Photopic Electroretinogram Negative Response between Young and Old Lewis Rats

 Purpose: To investigate and compare the latency and amplitude of the electroretinogram (ERG) photopic negative response (PhNR) between young and old Lewis rats. Methods: Thirteen Lewis rats were divided into two groups according to ages, young group (3-month old, n=5) and old group (24 month old, n=8). The ERGs of the left eyes were measured and the latency and amplitude of a-wave, b-wave and PhNRs were recorded and compared according to ages. The mean values between two groups were statistically analysed by t-test. Results: The latency of PhNRs was evidently prolonged in old group and showed significant difference (P<0.05). There was no statistically significant difference between two groups regarding the amplitude and latency, and no significant difference was noted in the amplitude of PhNRs. Conclusion: The prolonged latency of PhNR in aged rats possibly associate with the influence of aging upon retinal ganglion cell layer (RGCL).     

影响视网膜脱离患者视网膜功能的因素

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

Contribution of retinal ganglion cells to the mouse electroretinogram

Purpose

To quantify the direct contribution of retinal ganglion cells (RGCs) on individual components of the mouse electroretinogram (ERG).

Methods

Dark- and light-adapted ERGs from mice 8 to 12 weeks after optic nerve transection (ONTx, n = 14) were analyzed through stimulus response curves for a- and b-waves, oscillatory potentials (OPs), positive and negative scotopic threshold response (p/n STR), and the photopic negative response (PhNR) and compared with unoperated and sham-operated controls, as well as to eyes treated with 6-cyano-7-nitroquinoxaline-2,3-dion (CNQX).

Results

We confirmed in mice that CNQX intravitreal injection reduced the scotopic a-wave amplitude at high flash strength, confirming a post-receptoral contribution to the a-wave. We found that ONTx, which is more specific to RGCs, did not affect the a-wave amplitude and implicit time in either photopic or scotopic conditions while the b-wave was reduced. Both the pSTR and nSTR components were reduced in amplitude, with the balance between the two components resulting in a shortening of the nSTR peak implicit time. On the other hand, amplitude of the PhNR was increased while the OPs were minimally affected.

Conclusion

With an intact a-wave demonstrated following ONTx, we find that the most robust indicators of RGC function in the mouse full-field ERG were the STR components.     

Photopic negative response of the human ERG: losses associated with glaucomatous damage

PURPOSE: To evaluate in glaucomatous eyes the photopic electroretinogram (ERG) negative response (PhNR), a component that follows the b-wave peak and is thought to be correlated with inner retinal activity. METHODS: Eleven patients with open-angle glaucoma (OAG) and moderate field loss (Humphrey 30-2 [Humphrey Instruments, San Leandro, CA] mean deviation < or = -6 dB), eight with ocular hypertension (OHT), and eight age-matched normal subjects were tested. Optic discs of patients and control subjects were evaluated by confocal scanning laser ophthalmoscopy. ERGs were recorded to long-duration stimuli (250 msec) of photopic luminance (78 candelas [cd] /m2), presented in the macular region (12 degrees x 12 degrees field size) on a steady, adapting background. Amplitudes of the a-wave and b-wave and the PhNR were measured. Pattern reversal ERGs to 30-minute checkerboards were also recorded from patients and control subjects. RESULTS: Compared with control subjects, patients with OAG showed reduced PhNR (average reduction: 62%, P < 0.01), but normal a- and b-wave amplitudes. In patients with OHT, PhNR and a- and b-wave amplitudes did not differ from control values. In individual patients with OAG, PhNR amplitudes were correlated positively with pattern ERG amplitudes (r = 0.80; P < 0.01) and central (12 degrees) perimetric mean deviations (r = 0.68; P < 0.05) and negatively with cup-to-disc area ratios (r = -0.79; P < 0.01) and cup shape measures (r = -0.78; P < 0.01). CONCLUSIONS: Similar to that found in monkeys with experimentally induced glaucoma, the PhNR is selectively altered in human glaucoma. The correlation between PhNR losses and clinical parameter abnormalities suggests that this component depends on inner retina integrity and may be of clinical value for detecting glaucomatous damage.     

Abnormalities of the photoreceptor-bipolar cell synapse in a substrain of C57BL/10 mice

PURPOSE: A preferential loss of ERG b-wave was detected in a substrain of C57BL/10 mice. Electroretinographic and histologic techniques were used to investigate this hitherto unknown retinopathy. METHODS: ERGs were obtained from normal and affected C57BL/10. C57BL/6 mice served also as controls. a-Wave and c-wave analyses were performed. Microscopic investigations were done at two different ages. RESULTS: In the scotopic ERG, a severe reduction of the b-wave amplitude could be observed, whereas the a-wave was only moderately attenuated ("negative ERG"). With age, the a-wave amplitude further decreased, but the rate of reduction was comparable to normals. Oscillatory potentials were severely altered, and the photopic ERG was absent. The ERG c-wave was comparable to normal. ERG a-wave analysis also revealed a reduced maximum amplitude, but no significant difference of receptor sensitivity. Light microscopy revealed a thinning of all retinal layers but mostly of the outer plexiform layer. The number of photoreceptor nuclei was reduced by one third. Electron microscopy revealed a profound loss of ribbon-shaped synapses between rod and rod-bipolar cells and severely abnormal ribbons in the case of cones. CONCLUSIONS: The so-called negative ERG was associated with alterations in the synaptic layer between rods and rod bipolars. The absent cone ERG may be due to the altered cone-on-bipolar synapses. The overall thinning of the retina as well as the moderately reduced scotopic a-wave amplitude remain unexplained.     

Focal macular photopic negative response in patients with optic neuritis

Purpose

To investigate, by focal macular electroretinography (ERG), the change of photopic negative response (PhNR) in the recovery of visual function in patients with optic neuritis.

Methods

Focal macular ERG was recorded from nine patients with acute optic neuritis (38.6±10.2 years). The photostimulator device projected 15° visual angle spotlight onto the macula. Focal macular ERG recording was performed at the onset and at 1 month and 6 months after the onset of optic neuritis. The results were compared between each recording for seven of the patients.

Results

All patients decreased in the vision below 20/100 and had central scotoma. Vision improved more than 20/20 within 1 month and full-visual field recovered within 6 months after the onset in all patients. The amplitude of the a-wave, b-wave, and PhNR of focal macular ERG at the onset was significantly attenuated in eyes with optic neuritis (66.8±15.5, 65.8±17.7, and 65.2±14.4% of normal control, respectively). The amplitude of the a-wave and b-wave increased gradually after steroid pulse therapy. The increase in a-wave amplitude was significant at 6 months (P=0.046), whereas the PhNR amplitude did not show any significant change over 6 months after the onset of optic neuritis.

Conclusions

Our results suggest that inflammation at the onset of optic neuritis leads to functional deficits that extend to at least the inner nuclear layers of the retina, and that all but the ganglion cell layers of retina recover.     

Photopic ERG negative response from amacrine cell signaling in RCS rat retinal degeneration

PURPOSE: The authors investigated photopic electroretinographic changes during degeneration in the Royal College of Surgeons (RCS) and transgenic P23H rhodopsin rat models, including the cellular origins of a large corneal-negative component that persists in the RCS rat. METHODS: Photopic and scotopic electroretinograms (ERGs) were recorded from dystrophic RCS (RCS-p(+)/Lav) rats (4-18 weeks old) and transgenic rhodopsin Pro23His line 1 (P23H) rats (4-30 weeks old). Age-matched congenic (RCS-rdy(+)p(+)/Lav) and Sprague-Dawley rats were used as controls. N-methyl-DL-aspartic acid (NMA), dopamine, and gamma-aminobutyric acid (GABA) were injected intravitreally, and optic nerve sectioning (ONS) was performed to suppress or remove inner retinal neuron activity. Retinal morphology for cone cell counts and immunohistochemistry for quantification of Kir4.1 channels were performed at various stages of degeneration. RESULTS: As degeneration progressed, the photopic ERG of RCS dystrophic rats was distinctly different from that of P23H rats, primarily because of the growth of a corneal-negative response (RCS-NPR) after the b-wave in RCS rats. This response had a peak time similar to the photopic negative response (PhNR) in controls but with a more gradual recovery phase, and it was not affected by ONS. The PhNR in P23H rats declined linearly with the b-wave. NMA and GABA eliminated the RCS-NPR and uncovered a larger b-wave in RCS rats at late stages of degeneration, but NMA had little effect on the ERG in P23H rats. The NMA-sensitive negative response in RCS rats declined with age more slowly than did the NMA-isolated b-wave. The density of Kir4.1 channels at the endfeet of Müller cells and in the proximal retina increased significantly between 6 to 10 weeks and 14 weeks of age in the RCS rat retina but not in the P23H rat retina. CONCLUSIONS: The photopic ERG of the dystrophic RCS rat retina becomes increasingly electronegative because of an aberrant negative response, originating from amacrine cell activity, which declines more slowly than the b-wave with degeneration. The absence of this response in the P23H rat indicates that the inner retinal cone pathway pathology is different in the two models. A relative increase in Kir4.1 channels on Müller cells of RCS retina may contribute to the enhanced negative ERG response in the RCS rat.     

Analysis of the photopic electroretinogram recorded before and after dark adaptation

To evaluate the effect of a long period of dark adaptation on the light-adapted electroretinogram (ERG), photopic ERGs were recorded before (light-adapted) and immediately after (light-readapted) 15 minutes of dark adaptation. The amplitude of the b-wave in the light-readapted ERG was 48% +/- 4% of that in the light-adapted ERG, and the peak time of the b-wave in the light-readapted ERG was delayed by an average of 3.49 +/- 1.09 ms. Segmental analysis of the b-wave showed that the last segment of the ascending limb of the b-wave (from the second oscillatory potential [OP] to the peak) was attenuated the most (61% +/- 8%). In fact, the reduction in the amplitude of the last segment alone accounted for more than 60% +/- 13% of the overall reduction observed for the entire b-wave. This last segment appears to correspond to OP4 in the 100- to 1000-Hz recordings. The amplitude of OP4 in the light-readapted ERG was 56.5% +/- 10% of that in the light-adapted ERG, a similar reduction to that observed for the last segment of the 1- to 1000-Hz b-wave. The results strongly support the concept that the b-wave of the photopic ERG may actually represent a composite of potentials whose individual contributions are best visualized when the ERG is recorded with the 100- to 1000-Hz bandwidth.     

Functional changes in rod and cone pathways after photoreceptor loss in light-damaged rats

PURPOSE: To determine the functional changes in the rod and cone pathways after photoreceptor loss by continuous light exposure. METHODS: Fifty-four male Sprague-Dawley rats were exposed to diffuse fluorescent light of 2000 lux for 24 or 48 hr. Two weeks after the light exposure, full-field scotopic and photopic electroretinograms (ERGs) were elicited by different stimulus intensities with a maximum luminance of 0.84 log cd-s/m2. The amplitudes of the a- and b-waves of the scotopic ERGs and the b-wave of the photopic ERGs were measured. The animals were sacrificed after the ERG recordings, and the number of surviving rod and cone nuclei in the outer nuclear layer was counted. RESULTS: The logarithm (log) of the amplitudes of the maximum rod a-wave (rod Va(max)) and b-wave (rod Vb(max)) was reduced monotonically with a decrease in the rod nucleus counts (p < 0.0001). The regression line for the rod Va(max) decrease was significantly steeper than that for the rod Vb(max) (p < 0.005). The maximum b-wave amplitudes of the photopic ERGs (cone Vb(max)) were significantly correlated with the number of cone nuclei in a log-linear fashion. The slopes of the regression lines for the rod Vb(max) and cone Vb(max) were 0.0067 and 0.0140, respectively, which indicates that the amplitude of the cone b-wave was more severely affected than that of the rod b-waves by light-induced photoreceptor degeneration (p < 0.005). CONCLUSIONS: The amplitudes of the rod and cone ERGs were correlated with rod and cone nuclei counts in a log-linear fashion in light-damaged rats. The functional loss from the photoreceptor death had a greater effect on the cone pathway than on the rod pathway when the retinal function was assessed by the b-wave.     

Hypoglycemia increases the sensitivity of the cat electroretinogram to hypoxemia

Kang Derwent and Linsenmeier (2000) reported that the a- and b-waves of the cat electroretinogram (ERG) are resistant to hypoxemia, at least for PaO2 above 40 mm Hg. The a-wave may be resistant because the photoreceptor can increase glycolysis during hypoxemia. This hypothesis was tested by making the animal hypoglycemic, which should minimize the ability of the photoreceptor to switch to glycolysis. The ERG of dark-adapted anesthetized cats was recorded between an Ag/AgCl electrode in the vitreous humor and a reference electrode near the eye. Responses to bright flashes of diffuse white light were recorded at 3-min intervals during hypoxic episodes at three levels of blood glucose. The moderate hypoglycemia (50 to 70 mg/dl) had a relatively small effect on the a-wave amplitude. Furthermore, the a-wave amplitude increased transiently by 16 +/- 7% within 30-40 min of the start of severe hypoglycemia (20 to 40 mg/dl), before recovering to near normal. Severe hypoglycemia alone decreased the b-wave amplitude by 15 +/- 13%. Combined hypoxemia and hypoglycemia decreased the b-wave amplitude more than the a-wave amplitude. At all levels of blood glucose, b-wave decreases began at a higher PaO2 than the a-wave changes. For both the a- and b-waves, hypoxemic effects began at higher PaO2 when the animal was hypoglycemic. The increased sensitivity to hypoxemia during severe hypoglycemia suggests that a switch from oxidative to glycolytic metabolism ordinarily protects the retina from moderate hypoxemia. Because the a- and b-waves were affected to different degrees and at different PaO2s, it is unlikely that inner retinal changes are caused completely by changes in the photoreceptor.     

A composite nature for the photopic b-wave of the human electroretinogram as evidenced by the use of the 60 Hz notch filter

The impact of the 60 Hz notch (rejection) filter was examined in typical photopic electroretinograms recorded with two different bandwidths: 1-1000 Hz and 100-1000 Hz. The peak times of the major ERG components (a- and b-waves) are not modified by the line filter. The amplitude of the b-wave decreases by 30%, and the morphology of the ERG wave changes slightly. Segmental analysis of the ascending limb of the b-wave reveals that the sole reduction in the amplitude of its first step (from the a-wave trough to the peak of the first oscillatory potential) accounts for more than 70% of the overall reduction measured for the b-wave. Similar results are also found in ERGs recorded with the 100-1000 Hz bandwidth. The data suggests that the b-wave of the ERG should be considered as a composite of potentials rather than as a single potential.