The Decline of the Photopic Negative Response (PhNR) in the Rat after Optic Nerve Transection

Purpose: To investigate the contribution to the photopic negative response (PhNR) of the electroretinogram (ERG) by retinal ganglion cells (RGCs). The PhNR was assessed longitudinally following optic nerve transection (ONTx). Methods: Photopic ERGs were recorded from each eye of an anesthetized (ketamine/xylazine, 60 mg/kg and 5 mg/kg) Brown Norway rat using custom made electrodes (PT-IR Tef., A-M System Inc). ERGs were elicited using green Ganzfeld flashes (11.38 scd/m², 22.76 cds/m²) and a rod suppressing green-background (40 cd/m²). PhNRs were compared before and after optic nerves were transected. Cresyl violet stained retinal flatmounts were used to estimate cell loss in the ganglion cell layer 3 and 15 weeks after optic nerve transection. The pharmacological effect of 1.3 μM intravitreal TTX on the PhNR was also evaluated. Results: There was a significant loss (p <0.05) in the PhNR of 20, 36, 34, 35, 48, 48 and 56% for ONTx eye versus the contralateral eye, at post ONTx times of 24 h, 1, 2, 3, 4, 8 and 15 weeks. B-wave amplitudes of ONTx eyes were not significantly different from the control eyes. In ONTx eyes, mean cell loss in the retinal ganglion cell layer was 27 and 55% at the 3 week and 15 week time periods. In the eyes with ONTx, the decline of PhNR amplitudes was correlated positively with RGC loss (r = 0.98; p < 0.01). Thirty minutes after intravitreal TTX injection, the PhNR was significantly reduced (57%, p<0.01). Conclusions: There was a time-dependent decline in the PhNR after ONTx, as exemplified by a 35% reduction from 1–3 weeks, a 48% decline for 4–8 weeks and a 56% decline after 15 weeks. The correlation between the decline in the PhNR and retinal ganglion cell loss suggests that the PhNR depends on inner retina integrity and the PhNR may be important biological signal or detecting glaucomatous damage and the monitoring of RGC function changes in early glaucoma.     

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).     

The Photopic ERG of the Albino Guinea Pig (<Emphasis Type="Italic">Cavia porcellus</Emphasis>): A Model of the Human Photopic ERG

Altricial rodents such as rats and mice are probably the most widely used animal model in the electroretinogram (ERG) literature. However, while the scotopic responses of these rodents share obvious similarities with that of humans, their photopic electroretinograms are strikingly different. For instance, the photopic ERGs of rats and mice include, when measurable, a minimal a-wave, while the b-wave is of much larger amplitude than that of humans. The purpose of this study is to present the albino guinea pig which is like humans, is a precocial animal, and is a better rodent model of the human photopic ERG. In order to investigate the above, photopic electroretinograms and oscillatory potentials, obtained from guinea pigs and human subjects, were compared. Furthermore, in a subset of animals we injected, intravitreally, selective blockers of the ON- (L-2-amino-4-phosphonobutyric acid: L-AP-4; 10 mM) or OFF- (kynurenic acid: KYN; 50 mM) retinal pathways in order to mimic similar retinal disorders found in human. Based on our results, we believe that, compared to rats and mice, the photopic (cone-mediated) ERG of the guinea pig clearly represents a superior rodent model of the human photopic ERG.     

Clinical Application of Photopic Negative Response of the Flash Electroretinogram in Primary Open-angle Glaucoma

 PURPOSE: To evaluate the diagnostic performance of the photopic negative response (PhNR) for the detection of primary open-angle glaucoma (POAG). METHODS: Fifty-two normal subjects (52 eyes) and 173 POAG patients (173 eyes) were studied. The PhNR was elicited using a white stimuli on a white background. The mean deviation (MD) and pattern standard deviation (PSD) of the visual field were measured using standard automated perimetry (SAP). Spectral domain optical coherence tomography (SD-OCT) was used to measure the mean thickness of the retinal nerve fiber layer (RNFL). RESULTS: In the glaucoma group, as compared to the normal group, the amplitudes of a-waves, b-waves and PhNR were significantly smaller (P<0.001), and the PhNR implicit time was significantly longer (P=0.004). The MD, PSD and mean thickness of the RNFL were significantly correlated with the amplitude of the PhNR (P<0.001). The area under the receiver operating characteristic curve (AUCs) for the amplitudes of a-waves, b-waves and PhNR were 0.853, 0.830 and 0.918, respectively. When the specificity was ≥95%, the sensitivities were 60.4%, 54.2% and 85.4% respectively. CONCLUSION：The PhNR amplitude was reduced even when the loss in visual field sensitivity was mild, which suggests that PhNR might be a useful indicator of early glaucoma disease.       

Changes of Oscillatory Potentials and Photopic Negative Response in Patients with Early Diabetic Retinopathy

Purpose

To investigate the clinical significance of the oscillatory potentials (OPs) and photopic negative response (PhNR) of the electroretinogram (ERG) in patients with early diabetic retinopathy.

Methods

One hundred two diabetic patients with diabetic retinopathy at different stages were examined. Thirty-two age-matched normal controls were also studied. Full-field maximal and photopic cone ERGs were recorded. The amplitudes and implicit times of the OPs, cone b wave, and PhNR were compared at the different stages of diabetic retinopathy.

Results

The a and b wave amplitudes of the maximal scotopic ERGs remained unchanged despite advancing stages of retinopathy, but the OP amplitudes were significantly attenuated even at an early stage of diabetic retinopathy. The amplitudes of both the PhNR and cone b wave were reduced at an early stage of diabetic retinopathy. Analysis of the receiver operating characteristic curves demonstrated that the amplitudes and implicit times of the OPs were more sensitive and specific than those of the PhNR in detecting changes of retinal function in the early stages of diabetic retinopathy.

Conclusions

The amplitudes of the OPs and PhNR progressively decrease with the progression of diabetic retinopathy. The PhNR amplitudes were reduced along with the cone b wave, indicating that earlier change of the PhNR in diabetic patients reflects reduced input to the retinal ganglion cell from the distal retina. The amplitudes and implicit times of the OPs are better indicators than those of the PhNR in detecting functional decreases in patients with early diabetic retinopathy.?Jpn J Ophthalmol 2006;50:367–373 © Japanese Ophthalmological Society 2006     

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. Copyright © 1996 Elsevier Science Ltd.     

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.     

ERG Components of Negative Polarity from the Inner Retina and the Optic Nerve Response

ERG components of negative polarity in the light-adapted and in the dark-adapted inner retina are reviewed from a clinical perspective and include consideration of experimental research. Field potentials are inherently complex including summating contributions from specialized neurons as well as from glial elements. This property applies to the PERG, PhNR and to the STR. Experimental research can contribute to identifying the sites/cells of origins i.e. by determining depth profiles and by pharmacological manipulation. Intraretinal microelectrode-studies and pharmacological dissection of light-evoked responses have elucidated the origin of field potentials from the retinal pigment epithelium to the retinal ganglion cells. Thresholds for dark-adapted response components have been compared. Attenuation of the STR by anesthesia was found in cats in vivo when compared to threshold intensities used in isolated eye preparations in vitro, suggestive of depression of inner retinal activity by anesthetics. Evidence has been presented for antidromically elicited retinal responses of negative polarity that resemble the STR and summate with the light-evoked retinal response. This observation supports the notion that negative field potentials and components as recorded in the vitreous and at the cornea receive contributions from retinal ganglion cells. The weight of this contribution appears to vary among species, at least concerning the STR. The ocular negative reponses from the inner retina are compared to cortical excitatory mechanisms generating negativity in the baseline of the EEG.     

Spectral characteristics of the PhNR in the full-field flash electroretinogram of normals and glaucoma patients

Flash electroretinogram responses were measured in normal subjects to different chromatic combinations of flashes and backgrounds. The amplitudes of the flash response components were measured at different flash strengths and could be described by a generalized Naka-Rushton function. The measurements were repeated at different background luminances to study adaptation effects. It was found that when flash strength and background luminance were expressed in photometric terms (cd s/m2 and cd/m2, respectively), then the responses were very similar for all chromatic combinations with the exception of the condition in which blue (peak wavelength 458 nm) was flashed upon an orange (peak wavelength 591 nm) background. We propose that in this condition, a second (possibly S-cone or rod-driven) mechanism intrudes. The negative response after the b-wave (here called “photopic negative response” or PhNR for all conditions) is thought to reflect ganglion cell activity and was also largest at this condition. Responses were measured to the 458 nm flash on 591 nm background and the reversed combination in a population of 39 normal subjects and 49 glaucoma patients. It was found that the PhNR amplitude was affected by glaucoma in all conditions. Other component parameters, reflecting responses and adaptation dynamics, were not altered. The best stimulus condition among the conditions used to separate the PhNR amplitude of normals and patients was a 1 cd s/m2 458 nm flash on a 10 cd/m2 591 nm background.     

低温对眼电生理的影响

正常有色兔30只,分为37℃、0℃、-5℃三组,经封闭式玻璃体切除术后,采用三种不同温度灌注1小时。于术前及术后1周、2周、1月分别作各眼明暗适应,不同强度闪光视网膜电图(ERG),所得a、b波振幅数据输入电子计算机进行差异性分析,显示-5℃在术后1周ERG的a波振幅与术前有显著性差异。提示过低温度会损害视网膜功能,在眼低温玻璃体手术中不宜采用。     

视网膜电图明视负波反应的研究及其临床应用

视网膜电图明视负波反应（PhNR）是在明适应条件下,用亮光刺激时,紧接着b波缓慢出现的一个负相波。在蓝光背景下用红光刺激,则可引出振幅更大的PhNR。它是一种新的视觉电生理检查指标,可以特异性地反映视网膜神经节细胞及其轴突的生物电活动。本文就PhNR的研究进展及其在青光眼、视网膜、视神经病变中的应用作一综述。