利用锥体细胞失功能大鼠和先天性静止性夜盲大鼠对视锥与视杆通路振荡电位的分离研究

背景 振荡电位(OPs)是评估视网膜缺血缺氧性疾病视网膜功能变化的重要工具,利用视网膜退行性病变动物模型对视锥、视杆通路起源的OPs特点进行研究非常重要. 目的 在两种自发性视网膜退行性病变模型大鼠中分离视锥、视杆通路,对比分析视杆、视锥通路起源的OPs波的特点. 方法 采用雄性SD大鼠、锥体细胞失功能(RCD)大鼠、先天性静止性夜盲(CSNB)大鼠各6只,以RETI-scan视觉生理记录系统分别在暗适应(12h)和明适应(10 min)条件下,用不同强度的刺激光(-35、-25、-15、-5、0、5 db)进行刺激,记录各组大鼠的闪光视网膜电图(FERG),通过Matlab 7.0的Butterworth滤波提取OPs,采用快速傅里叶变换(FFT)对所得OPs进行频谱分析.结果 暗适应条件下SD大鼠和RCD大鼠的ERG均可见a波和b波,但CSNB大鼠b波阙如;明适应条件下,SD大鼠和CSNB大鼠可见b波,但RCD大鼠各波阙如.暗适应较高刺激光强度下,SD大鼠和RCD大鼠均有低频(主频)和高频(次频)两个明显的频峰,分别为75 ～ 110 Hz、90～120 Hz和90～ 120 Hz、110 ～ 135 Hz;不同刺激光强度下,CSNB大鼠只有一个频峰,为70～100 Hz.而明适应不同刺激光强度下,SD大鼠和CSNB大鼠均只有一个频峰,分别为75～95 Hz和70～85 Hz.明适应条件下与SD大鼠比较,CSNB大鼠b波隐含时延长,b波振幅明显下降,差异均有统计学意义(P＜0.05);暗适应条件下,RCD大鼠b波隐含时和振幅与SD大鼠比较,差异无统计学意义(P＞0.05);与SD大鼠比较,RCD和CSNB大鼠OPs波振幅下降,隐含时延长,差异均有统计学意义(P＜0.05);明适应条件下不同刺激光强度下CSNB大鼠OPs波的隐含时明显长于SD大鼠,振幅明显低于SD大鼠,差异均有统计学意义(P＜0.05). 结论 视锥、视杆通路起源的OPs有不同特性,自发性视网膜退行性改变大鼠的视杆OPs有两个频峰,正常情况下,视杆通路对OPs的贡献比视锥通路大.     

Light adaptation, rods, and the human cone flicker ERG.

During the course of light adaptation, the amplitude and implicit time of the human cone ERG change systematically. In the present study, the effect of adapting field luminance on these ERG changes was assessed, and the hypothesis that light adaptation of the rod system is the primary determining factor was evaluated. Cone ERG responses, isolated through the use of 31.1-Hz flicker, were obtained from two visually normal subjects, initially under dark-adapted conditions and then repeatedly for 30 min following the onset of each of a series of ganzfeld adapting fields with luminances that ranged from -1.2 to 2.1 log cd/m2. The increase in flicker ERG amplitude and decrease in implicit time during light adaptation were greatest at the highest adapting field luminances. Photopically equivalent achromatic and long-wavelength adapting fields induced comparable increases in flicker ERG amplitude, while scotopically equivalent adapting fields had considerably different effects. This latter finding demonstrates that the rod system is not a major determinant of the adaptation-induced increase in cone ERG amplitude.     

Slow and fast rod ERG pathways in patients with X-linked complete stationary night blindness carrying mutations in the NYX gene

PURPOSE: To study the slow and fast rod signals of the scotopic 15-Hz flicker ERG in patients carrying mutations in the NYX gene, which has been recently identified as the cause of the complete form of congenital stationary night blindness, CSNB1. METHODS: Twenty eyes of 11 patients with CSNB1 who had nondetectable standard ERG rod b-waves were involved in the study. Scotopic ERG response amplitudes and phases to flicker intensities ranging from -3.37 to -0.57 log scotopic trolands. sec (scot td. sec) were measured at a flicker frequency of 15 Hz. ERG signals to flicker intensities between -3.37 and -1.97 and between -1.17 and -0.57 log scot td. sec were considered to represent primarily the slow and fast rod ERG pathway, respectively. Additionally, standard ERGs were performed. Twenty-two normal volunteers served as control subjects. RESULTS: For the slow rod ERG pathway, all patients exhibited ERG signals that were indistinguishable from noise. Accordingly, there was no systematic phase behavior for the slow rod signals. For the fast rod ERG pathway, the signals were significantly above noise, but they were significantly reduced in amplitude and advanced in phase. CONCLUSIONS: There is evidence that the slow and the fast rod ERG signals can be attributed to the rod bipolar-AII cell pathway and the rod-cone-coupling pathway, respectively. The current study provides evidence to suggest that a defective NYX gene product (nyctalopin) prevents detectable signal transmission through ON rod bipolar cells, but there is a residual transmission through rod-cone gap junctions in CSNB1, possibly through the OFF cone pathway.     

Changes in the harmonic components of the flicker electroretinogram during light adaptation

Purpose

To evaluate the nature and extent of changes in the fundamental and harmonic components of the 31-Hz flicker electroretinogram (ERG) during light adaptation.

Methods

Full-field ERGs were recorded from five visually normal subjects (ages 21–60 years). Following 30 min of dark adaptation, the subjects were exposed to a uniform adapting field of 50 cd/m². The field, which was presented for approximately 15 min, was intermittently modulated sinusoidally at 31.25 Hz. The ERG was recorded during the sinusoidal modulation, and Fourier analysis was used to obtain the amplitude and phase of the fundamental (F), second (2F), and third (3F) harmonic response components.

Results

F amplitude increased by almost a factor of two over approximately 6 min (time constant, τ, of 3.0 min). The 2F amplitude increased by a smaller amount, a factor of 1.4, and the time-course was approximately eight times faster than that of F (τ = 0.4 min). The 3F amplitude increased by a factor of 4.6, an increase that was larger than F or 2F, with a time-course that was between that of F and 2F (τ = 1.4 min). F phase was unaffected by light adaptation, whereas the 2F and 3F phases both increased by approximately 45° over similar time-courses (τ = 2.0 min).

Conclusions

Light adaptation had different effects on the fundamental, second, and third harmonic components of the 31-Hz flicker ERG, which resulted in a change in waveform shape during light adaptation. The previously reported flicker ERG amplitude growth is driven primarily, but not entirely, by changes in the fundamental.     

Phenotypic expression of the complete type of X-linked congenital stationary night blindness in patients with different mutations in the <Emphasis Type="Italic">NYX</Emphasis> gene

PURPOSE: To describe the clinical phenotype of the complete type of X-linked congenital stationary night blindness (CSNB1) with different types of mutations in the NYX gene. METHODS: The clinical and genetic data from 18 male patients with eight different mutations from two ophthalmological institutes were reviewed. The variability in refractive error, reduced visual acuity and full-field electroretinogram (ERG) recordings was examined. RESULTS: Parameters were quantitatively analyzed based on the classification of mutations according to their predicted effect on protein structure and function. CSNB1 patients with mutations changing structurally conserved residues ( n=12) tended to have a lower degree of myopia than patients with mutations of non-conserved residues ( n=6). Visual acuity loss and the 30 Hz flicker ERG recordings were similar in the two groups. Values for the b/a amplitude ratio tended to be clustered in patients carrying the same mutation. Refractive error and the b/a amplitude ratio were highly correlated between the two eyes of an individual. CONCLUSIONS: These data suggest correlations between phenotypic expression in CSNB1 and individual genotypes as well as class types of mutations based on the extent of structural amino acid conservation. A high inter-eye correlation suggests that other genetic or environmental factors, rather than chance, play a part in determining the phenotypic diversity in CSNB1.     

正常人闪烁光视网膜电图和闪烁光视诱发电位的定量分析

目的探讨闪烁光视网膜电图和闪烁光视诱发电位在正常人的变化规律。方法记录51例正常人10Hz闪烁光VEP和30Hz同陈光ERG，使用离散富里叶法分析波形的振幅和相位。结果应按20岁以下组、20～40岁组和40岁以上组对正常入进行记录。10Hz闪烁光VEP基波、二次谐波的振幅，二次谐波的相位，30Hz闪烁光ERG基波的振幅和相位是分析的主要指标。结论闪烁光视网膜电图和闪烁光视诱发电位能进一步分离视锥细胞功能，对视功能进行更好评价。     

闪烁光ERG和闪烁光VEP对玻璃体混浊患者的视功能评价

对34例玻璃烽混浊患者术前30Hz闪烁光ERG、10HZ闪烁光VEP和30Hz闪烁光VEP的结果，使用离散博里叶分析法，提取波形特征值振幅和相位，与术后视力进行比较．多元回归分析表明：ERG与VEP的振幅都与术后视力呈正相关，复合相关系数r=0.718(P＝0.0076)；相位则无相关。联合应用ERG和VEP检测时术后视力有较好的预测作用。 （中华眼底病杂志，1995，11：159-161）     

Cone function in congenital nyctalopia

A patient with congenital stationary night blindness (CSNB) (Schubert-Bornschein type) transmitted as an autosomal recessive trait was studied with several tests of electrical function as well as a variety of psychophysical procedures. Comparison of the patient's present findings with those obtained 23 years earlier showed that while rod thresholds have remained the same, cone sensitivity has decreased. Subjective flicker thresholds obtained following a bleach were unchanged during the course of dark adaptation. The absence of rod-cone interaction, together with an absent scotopic b-wave, implies that the defect is in the mid-retinal layers. Further, the absence of oscillatory potentials in the photopic electroretinogram (ERG) suggests that the interplexiform cell may be implicated in some manner. The focal ERG of the CSNB patient showed normal amplitude and normal phase delays, supporting the idea that the focal ERG samples primarily cone photoreceptor activity.     

Visual adaptation and the cone flicker electroretinogram

This study examined the hypothesis that changes in the response properties of the human cone ERG during light adaptation represent the recovery of cone system responsiveness toward a dark-adapted value after an initial decrease in responsiveness at adapting field onset. The electroretinographic (ERG) responses to 31.1 Hz flicker were obtained under both dark-adapted and light-adapted conditions for stimulus luminances ranging from -1.42(-)+0.82 log cd sec/m2. At low stimulus luminances, flicker ERG amplitudes were larger under dark-adapted than under light-adapted conditions, consistent with the hypothesis. However, at high stimulus luminances, flicker ERG amplitudes obtained under light-adapted conditions were approximately double those recorded from the dark-adapted eye. Therefore, the increase in cone ERG amplitude that occurs during light adaptation at high stimulus luminances does not represent a return toward a dark-adapted level but instead entails a substantial enhancement above the dark-adapted value, by a mechanism that is presently unidentified.     

高度近视眼视功能状态与屈光度相关性的临床研究

目的:观察不同近视屈光度下,高度近视眼视功能状态的改变,寻找不同近视屈光度对高度近视眼功能、形态损害的相关早期客观敏感指征。方法:采用视野的中心低视力程序(LVC)和黄斑程序(M2,C08,TG2),以及视觉电生理系统中反映眼视功能状态的指标进行定性定量观察,包括单次视锥-视网膜电图(ERG)、30Hz闪烁ERG、P-VEP,多焦视网膜电图中一阶反应1、2环。结果:随近视屈光度的增加,视野的光敏感度(MS)下降;视觉电生理中PVEP、单次视锥细胞和30Hz闪烁b波、1环和2环振幅密度、1环b波振幅和2环a、b波振幅和潜时延长有下降(P<0.05);多元逐步回归分析提示,近视屈光度的数值与眼轴呈负相关关系,并与PVEP振幅呈正相关关系、与单次视锥b波潜时呈负相关关系。结论:视野、视觉电生理振幅可以较早检测到不同近视屈光度对视网膜功能的影响。     

A distinctive form of congenital stationary night blindness with cone ON-pathway dysfunction

PURPOSE: To characterize a distinctive form of congenital stationary night blindness (CSNB). DESIGN: Observational case report. PARTICIPANTS: A 30-year-old male with a history of night blindness, several members of his family, a patient with "complete" congenital stationary night blindness (CSNB1), and groups of age-similar control subjects. METHODS: Rod-system function was evaluated by measuring psychophysical dark-adapted thresholds, by recording dark-adapted electroretinograms (ERGs), and by fundus reflectometry. Cone-system function was evaluated by recording light-adapted ERGs, including those to sawtooth flicker, and by recording light-adapted visually evoked potentials (VEPs) to luminance increments and decrements. MAIN OUTCOME MEASURES: Dark-adapted thresholds, ERGs, rhodopsin double densities, Goldmann visual fields, and VEPs. RESULTS: The patient's visual acuity, visual fields, and color vision were normal. His peripheral dark-adapted thresholds were rod-mediated but elevated by approximately 3 log units above normal. Rhodopsin double density and bleaching recovery were normal. His dark-adapted maximal-flash ERG showed a "negative" waveform, in which the b-wave was more reduced in amplitude than the a-wave, although the a-wave amplitude was also reduced. The rod photoreceptors contributed to the patient's dark-adapted ERGs, as illustrated by the unequal responses to cone-matched stimuli. The patient's cone-mediated thresholds for long-wavelength stimuli were within the normal range. However, his light-adapted brief-flash b-wave was abnormal in amplitude and implicit time. Selective abnormalities of the ON responses of the cone system were apparent in the patient's reduced b-wave amplitude to rapid-on flicker with a normal response to rapid-off flicker, and his prolonged VEP latencies to increments but not to decrements. CONCLUSIONS: The overall pattern of findings distinguishes this patient from previously described forms of CSNB. The results suggest that two factors likely contribute to the patient's night blindness: (1) a rod phototransduction defect and (2) a postreceptoral defect. The results also indicate dysfunction within the cone ON pathway.     

Rapid and slow changes in the human cone electroretinogram during light and dark adaptation.

Changes in the response characteristics of the human cone electroretinogram (ERG) during light and dark adaptation were studied in two visually normal subjects. Cone ERG responses were isolated under all adaptation conditions through the use of 31 Hz flicker. To determine the time-course of changes in the cone ERG during adaptation, responses to stimuli of constant luminance were measured repeatedly during 15 min of exposure to an adapting field of 2.0 log cd/m2 and during 30 min of dark adaptation following adapting field termination. In addition, luminance-response functions were obtained before and immediately after adapting field onset, as well as before and immediately after adapting field termination. The results indicate that the human cone ERG is influenced by two major processes. One process has a relatively rapid time-course and serves to reposition the luminance-response function along the luminance axis following changes in ambient light levels. The second process, which has a slow time-course, scales response amplitudes during light and dark adaptation by the same proportion at all stimulus luminances. The results provide a framework for predicting the manner in which the cone ERG will change with alterations in the state of retinal adaptation.     

Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves

The purpose of this study was to determine the contributions of postreceptoral neurons to the light-adapted ERG of the Nob mouse, a model for complete-type congenital stationary night blindness (CSNB1) that lacks a b-wave from depolarizing bipolar cells. Ganzfeld ERGs were recorded from anesthetized adult control mice, control mice injected intravitreally with L-2-amino-4-phosphonobutyric acid (Control APB mice) to remove On pathway activity, and Nob mice. ERGs also were recorded after PDA (cis-2,3-piperidine-dicarboxylic acid, 3-5mM) was injected to block transmission to hyperpolarizing (Off) bipolar and horizontal cells, and all third-order neurons. Stimuli were brief (<4ms, 0.4-2.5log sc td s) and long (200ms, 2.5-4.6log sc td) LED flashes (lambda(max)=513nm, on a rod suppressing background (2.6log sc td). Sinusoidal modulation of the LEDs (mean, 2.6log sc td; contrast, 100%; 3-36Hz) was used to study flicker ERGs. Brief-flash ERGs of Nob mice presented as long-lasting negative waves with a positive-going intrusion that started about 50ms after the flash and peaked around 120ms. Control APB mice had similar responses, and in both cases, PDA removed the positive-going intrusion. For long flashes, PDA removed a small, slow "d-wave" after light offset. With sinusoidal stimulation, the fundamental (F1) amplitude of control mice ERG peaked at 8Hz ( approximately 70microV). For Nob mice the peak was approximately 20microV at 6Hz before PDA and approximately 10muV at 3Hz or lower after PDA. F1 responses were present up to 21Hz in control and Nob eyes and 15Hz in Nob eyes after PDA. Between 3 and 6Hz, F1 phase was 170-210 degrees more delayed in Nob than control mice; phase was hardly altered by PDA. With vector analysis, a substantial postreceptoral input to the Nob flicker ERG was revealed. In control mice, the second harmonic (F2) response showed peaks of approximately 10mocrpV at 3Hz and 13Hz. Nob mice showed almost no F2. In summary, in this study it was found that in Nob mice, postreceptoral neurons from the Off pathway make a positive-going contribution to the light-adapted flash ERG, and contribute substantially to sinusoidal flicker ERG.     

Photometry in goldfish by electrophysiological recording: comparision of criterion response method with heterochromatic flicker photometry.

In everyday vision the eye commonly functions while its state of adaptation is continuously changing rather than being held constant as in most scientific studies. We measured spectral luminosity curves for goldfish by recording ERG and tectal evoked response. Continuously changing the state of adaptation had a large effect at tectal level, but comparatively little at ERG level. With changing adaptation the relation between light intensity and response amplitude showed gross hysteresis and nonlinearity at tectal level. This was not so marked at ERG level, and not at all at either level when adaptation was not changing.The widely-used criterion response method showed severe limitations when adaptation was changing. Heterochromatic flicker photometry was a more accurate, and considerably more sensitive (0.01 log unit) way of measuring the spectral luminosity curve. ERG and TER gave similar luminosity curves. These curves did not depend on flicker frequency (2.5–20 Hz), adaptation level (over 2.0 log units) or harmonic component. The luminosity curve was fitted by absorption spectra for cone photopigments: the red pigment dominated, and the blue contribution was negligible.     

Electroretinogram changes after scleral buckling surgery of retinal detachment

Objective To observe changes in visual function after a single scleral buckling surgery for rhegmatogenous retinal detachment (RD) by using ERG (electroretinogram). Methods One eye from 56 patients with rhegmatogenous RD was chosen. Forty-three corresponding normal fellow eyes from these patients were chosen as controls. Single scleral buckling surgery was carried out and a full-field ERG was performed before the surgery, and 1 and 6 months after surgery. Results The mean amplitude of ERG decreased and the latency (except for the a-wave) was delayed in the eye with a retinal detachment, and wavelets of the oscillatory potential decreased or were completely lacking. One month after surgery, the amplitudes of the a and b waves were noticeably improved (except for the 30 Hz flicker responses), but the latency (except for the a-wave) was still delayed. The ratio of b/a (mixed response) increased 1 month after surgery, with no further changes thereafter. The amplitude of the scotopic b wave was 58.1% of the control eyes, while the 30 Hz flicker responses was only 45.8% of controls; the difference between the two responses was significant (P < 0.001). The number of oscillatory potential wavelets increased, but the total amplitude of the oscillatory potentials did not exhibit any obvious changes during the follow-up period (P = 0.20). In the 41 patients whose detachment involved the macula preoperatively, the amplitude of the 30 Hz flicker responses improved significantly after surgery (P = 0.037). Six months after the operation, the wave amplitudes were not significantly different from 1 month after surgery, but there was a tendency toward a decrease in the latency. Conclusions After reattachment of the retina, visual function showed dramatic improvement 1 month after the surgery. The postreceptoral responses recovered more than the a-wave. The rod system recovered more quickly and completely than the cone system during the follow-up period. The incomplete recovery observed by using ERGs indicates that there is irreversible damage that likely occurs following retinal detachment and surgery.     

Temporal aspects of the electroretinogram in cone-rod dystrophy

Twelve patients with cone-rod dystrophy were studied in terms of the temporal aspects of electroretinography (ERG).The peak time of scotopic b-wave was within normal limits in all patients, while the amplitude was reduced in nine patients. The normal peak time of the scotopic-b wave may help explain rod involvement with normal or only slightly elevated final rod thresholds of subjective dark adaptation.The peak time of photopic b-wave and 30-Hz flicker response was normal in four patients and significantly delayed or nonrecordable in eight patients. Such variations of peak time in photopic and 30-Hz flicker ERG may reflect the stage of the disease or may be caused by the different hereditary mode.     

Bull's-eye maculopathy and negative electroretinogram

The authors studied four patients with a bull's-eye maculopathy and otherwise normal fundus. A single-flash electroretinogram (ERG) with an intense white light stimulus in the dark showed a normal a-wave but reduced b-wave amplitude (negative ERG). Other findings common to all four patients were initially normal visual acuity, subsequent progressive decrease in visual acuity, mild to moderate deficiency of color vision, normal peripheral visual field, relatively well preserved cone ERG, normal 30-Hz flicker ERG, normal EOG, near emmetropia and selective involvement in males. Cone dystrophy, retinitis pigmentosa, congenital retinoschisis, congenital stationary night blindness, and Batten's disease were excluded. The correlation between this disease and benign concentric annular macular dystrophy is discussed.     

Dependence of cone b-wave implicit time on rod amplitude in retinitis pigmentosa

Computer-averaged full-field rod and cone electroretinograms (ERGs) were evaluated in 63 patients with retinitis pigmentosa and 116 normal subjects. Cone b-wave implicit times to 30 Hz white flicker and to 1.0 Hz white flashes on a white background were both inversely proportional to the log amplitude of the dark-adapted rod b-wave, even when controlling for the log amplitude of the dark-adapted cone b-wave. Cone ERGs were also obtained from a subset of 12 patients with retinitis pigmentosa in the presence of photopically-matched red and blue backgrounds that allowed direct assessment of the effect of rod function on cone b-wave implicit time in the patients. The effectiveness of the blue background in reducing cone b-wave implicit time relative to that obtained with the red background varied with the amplitude of the rod ERG. The results of both experiments suggest that delays in cone b-wave implicit time obtained with 30 Hz white flicker or with background adaptation in patients with retinitis pigmentosa are due, at least in part, to rod disease.     

Possible pathogenesis of congenital stationary night blindness

We reported a case of congenital stationary night blindness (CSNB) who showed Schubert-Bornschein type electroretinogram (ERG) in the right eye and nearly normal ERG in the left eye with absolute glaucoma. From the electrophysiological findings of both eyes and histological findings of the enucleated eye, we concluded that the mechanism of night blindness in CSNB is an abnormal inhibition in the bipolar cell layer. The experiments in rabbits by vincristine intravenous and intravitreous administrations did not give rise to a negative type ERG, but to a decrease of the amplitude of all ERG components. The lesion of CSNB which was reported to be responsible in the synaptic terminal by Ripps et al could not be confirmed.     

A form of congenital stationary night blindness with apparent defect of rod phototransduction

We report findings obtained from an individual with an unusual form of congenital stationary night blindness (CSNB). Although the rhodopsin density difference of this subject was normal, there was no evidence of rod-mediated visual function. Dark-adapted thresholds were cone-mediated, and dark-adapted electroretinograms (ERGs) represented activity of the cone system exclusively. ERG a- and b-waves obtained under light-adapted conditions were normal. The absence of a rod a-wave but the presence of normal rhodopsin density, in combination with normal cone function, indicates that this form of CSNB likely involves a defect of phototransduction that is limited to the rods. In addition, light-adapted b-wave responses to high luminance flashes were larger than dark-adapted responses, whereas a-wave amplitudes were reduced by light adaptation. These ERG results address proposed mechanisms by which light adaptation might enhance cone system responses.