Detection of glaucomatous damage using multifocal ERG

The first‐order kernel analysis in multifocal electroretinogram (mfERG) using low contrast stimulation is suggested as a way to detect the inner retinal responses in animal studies. In this case report, this protocol is applied to human patients with glaucoma to demonstrate the possibility of using mfERG as a tool to detect glaucomatous damage. Two patients with glaucoma were recruited and had mfERG measurements with the 103‐scaled hexagonal stimulus pattern at low (50 per cent) contrast. Their responses were analysed and compared with those from normal subjects with the mfERG measured under the same condition. In the normal subjects, there were obvious oscillatory components on the ascending and descending limbs of the first‐order kernel response to 50 per cent contrast. In the glaucomatous patients, the oscillatory component on the descending limb was obviously diminished. In addition, this component was significantly diminished in the quadrant with a glaucomatous visual field defect. This suggests that the low‐contrast stimulation condition in mERG measurement may provide a good way to detect glaucomatous damage and this may help in clinical diagnosis of glaucoma.     

Check size tuning of the pattern electroretingoram: a reappraisal

The pattern electroretinogram was recorded to checkerboard stimuli with a wide range of check sizes and two stimulus field sizes. Check sizes ranged from 0.25° to 7° (field size, 16°×14°) and 0.25° to 15° (field size, 32°×27°) in 14 and seven subjects, respectively. Reversal rate was 4.5/s. For minimal intrusion of blink artifacts the interrupted stimulation technique was employed. The P50 and N95 components of the pattern electroretinogram were evaluated separately. With both stimulus field sizes amplitude of P50 and N95 was maximal between 0.75° and 1°. With smaller check sizes the amplitude dropped monotonically. With larger check sizes field size played a role: with the 16°×14° field, P50 gradually dropped to 89% from 1° to 7°, which was paralleled by N95 only up to 7°, where N95 dropped to 81% (p<0.05). With the 32°×27° field, there was no significant difference in size dependency between P50 and N95 for large checks, both components staying constant from 1° to 15° We conclude that there is only minor large-check attenuation of the pattern electroretinogram, especially with a large field. The apparent field-size dependency may explain previous discrepancies in the literature.     

视网膜脱离手术复位后ERG的恢复

为探讨视网膜脱离手术复位后ERG的改变，对35例（35眼）患者进行手术前后ERG检测，结果表明；（1）视网膜脱离术前ERGa、b波幅明显低于有视网膜格子样变性而无脱离者。（2）手术复位后ERGa、b波幅随时间延长逐渐回升。（3）视网膜脱离范围二个象限以内者ERGa、b波幅回升高于二象限以上者。（4）手术范围一个象限以内者与超过一个象限者相比前者ERG恢复优于后者。（5）视网膜脱离时间2月以内与超过2月相比，ERG恢复前者明显优于后者。结果证实视网膜脱离术后ERG恢复与手术后时间、脱离范围、病程及手术范围密切相关。     

Macular oscillatory potentials in humans

Studies of the focal macular electroretinogram (ERG) have been made with special reference to oscillatory potentials (OPs) by using a fundus monitoring system in humans. Human macular OPs consist of 3 to 4 wavelets (mean peak interval, approximately 6.5 msec). The distribution of OPs in relation to those in a- and b-waves was studied. The amplitudes of a-waves, b-waves, and OPs of the upper macula were significantly larger than those of the lower macula. The distribution of OPs is relatively sparse in the fovea, becoming more dense than the a- and b-waves from the fovea toward the parafovea, and differing even more toward the perifovea. There was no statistical difference of amplitude in a- and b-waves between nasal and temporal macula. The amplitude of OPs in the temporal macula, however, was significantly larger than in the nasal macula. In some macular diseases, such as diabetic maculopathy, cystoid macular edema, or the convalescent stage of central serous chorioretinopathy, macular OPs were selectively reduced, leaving the a- and b-waves intact. Macular OPs can provide a new aspect of macular function and can be a sensitive indicator to assess that function in macular diseases.     

视网膜电图对玻璃体出血机化和玻璃体手术的意义

报告118例(133眼)由各种疾病引起的玻璃体出血机化患者的视网膜电图(ERG)检查结果,其中31例作了玻璃体手术,结果表明,ERG检查对玻璃体出血机化的患者,能客观地反映其网膜功能,并对玻璃体手术的预后有指导作用。术前ERG检查,a、b波下降越严重,视功能损害显著,术后视力的预后越差,同时证实,玻璃体机化膜是影响a、b波波幅和时间的一个因素。     

Influence of picrotoxin and strychnine on the spectral sensitivity of the turtle ERG b- and d-waves: II. Light adaptation

The aim of the present work was to investigate the role of GABA and glycine, the two main inhibitory neurotransmitters in the retina, in the spectral sensitivity coding under conditions of light adaptation. To study this question, spectral sensitivity curves, based on the turtle ERG responses to stimuli of different wavelengths, were constructed. The spectral sensitivity curves, obtained before and during treatment with picrotoxin (PT), a GABA_A antagonist, or with strychnine (ST), a glycine antagonist, were compared. Both PT and ST increased the b- and d-wave absolute sensitivity in a wavelength-dependent manner. PT significantly changed the shape of the b- and d-wave spectral sensitivity curves and the latter lost their peaks. It is concluded that, under conditions of light adaptation, GABA and glycine took part in the formation of the b- and d-wave spectral sensitivity curves, that both of them exerted an effect on the gain and that, furthermore, GABA had a well pronounced effect on the tuning of the spectral sensitivity curves.     

Disease-specific electrophysiological findings in adult ceroid-lipofuscinosis (Kufs disease)

Two adults with mild dementia and a history of memory loss and disequilibrium were seen in the eye clinic following complaints of acuity loss in the 20/30–20/70 (Snellen) range. Results from the fundus examination of one patient were entirely normal; the other showed minimal vascular attenuation and optic atrophy. Electrophysiology was remarkable: (1) Photopic ERG b-waves were reduced, delayed, and showed pronounced oscillations. (2) EOG light-rise potentials were absent or very small. (3) Binocular pattern-VER signals showed addition of the monocular signal. Scotopic ERG signals were normal. Brain biopsy and microscopy showed intercellular, autofluorescent ceroid deposits which provided a clear diagnosis of Kufs disease. Histology of model animal retinal cells show ceroid deposits in cell classes implicated by the human retinal signals. The cluster of electrophysiological results point toward early changes in the pigment epithelium and inner plexiform layer cells as a means of non-invasive diagnosis.     

PTEN loss in intraductal carcinoma of the prostate has low incidence in Japanese patients

Clinical and genomic features of prostate cancer (PCa) vary considerably between Asian and Western populations. PTEN loss is the most frequent abnormality in intraductal carcinoma of the prostate (IDC-P) in Western populations. However, its prevalence and significance in Asian populations have not yet been well studied. In the present study, we evaluated PTEN expression in IDC-P in a Japanese population and its association with ERG expression. This study included 45 and 59 patients with PCa with and without IDC-P, respectively, who underwent radical prostatectomy. PTEN loss was observed in 10 patients with PCa with IDC-P (22%) and nine patients with PCa without IDC-P (17%). ERG expression was relatively frequent in patients with PCa with PTEN loss, although a significant difference was not observed. The co-occurrence of PTEN loss and ERG expression was observed in four patients with PCa with IDC-P and one without IDC-P. PTEN loss and ERG expression did not affect progression-free survival, regardless of the presence of IDC-P. The frequency of PTEN loss in IDC-P is lower in Asian patients than in Western patients. Our results indicate that mechanisms underlying IDC-P in Asian populations are different from those of Western populations.     

High affinity of sigma1-binding sites for sterol isomerization inhibitors: evidence for a pharmacological relationship with the yeast sterol C8–C7 isomerase

1. The sigma-drug binding site of guinea-pig liver is carried by a protein which shares significant amino acid sequence similarities with the yeast sterol C₈–C₇ isomerase (ERG2 protein). Pharmacologically - but not structurally - the sigma₁-site is also related to the emopamil binding protein, the mammalian sterol C₈–C₇ isomerase. We therefore investigated if sterol C₈–C₇ isomerase inhibitors are high affinity ligands for the (+)-[³H]-pentazocine labelled sigma₁-binding site.
2. Among the compounds which bound with high affinity to native hepatic and cerebral as well as to yeast expressed sigma₁-binding sites were the agricultural fungicide fenpropimorph (K_i 0.005 nM), the antihypocholesterinaemic drugs triparanol (K_i 7.0 nM), AY-9944 (K_i 0.46 nM) and MDL28,815 (K_i 0.16 nM), the enantiomers of the ovulation inducer clomiphene (K_i 5.5 and 12 nM, respectively) and the antioestrogene tamoxifen (K_i 26 nM).
3. Except for tamoxifen these affinities are essentially identical with those for the [³H]-ifenprodil labelled sterol C₈–C₇ isomerase of S. cerevisiae. This demonstrates that sigma₁-binding protein and yeast isomerase are not only structurally but also pharmacologically related. Because of its affiliations with yeast and mammalian sterol isomerases we propose that the sigma₁-binding site is localized on a sterol isomerase related protein, involved in postsqualene sterol biosynthesis.

     

Development of receptoral responses in pigmented and albino guinea-pigs (Cavia porcellus)

We describe the postnatal development of the electroretinogram (ERG) receptoral response in the guinea pig. In addition, the time course and nature of maturation was compared between albino and pigmented strains to consider the role that melanogenesis might have in this process. Electroretinograms were collected on groups of albino and pigmented animals from postnatal day (PD) PD1 to PD60. A-wave amplitudes and implicit times were extracted from filtered data (0–75 Hz). Receptoral components were modelled using the delayed gaussian model of Hood and Birch [1] fitted as an ensemble to the raw data. Guinea pigs show saturated amplitudes (Rm_P3) that are 50% of adult values at birth, these mature by PD12. Receptoral delay (t_d) also undergoes some postnatal maturation, while phototransduction gain (log S) is adult-like at birth. Albino animals had significantly (p<0.05) larger Rm_P3 and log S across all ages. Guinea pigs have significant postnatal development in their receptoral response. Maturation of Rm_P3 implies a postnatal increase in rod outer segment length. Whereas the adult values of log S implies a mature phototransduction process at birth. We argue that the likely cause for the larger log S of albino eyes is compatible with theories of increased levels of internal light. Whereas the larger Rm_P3, even after allowing for increased light effectiveness, may reflect a lower ocular resistance in albino eyes due to their lower levels of melanin. Furthermore, decreased Rm_P3 and log S with age is observed in the pigmented group only and is consistent with increased ocular resistance due to melanin development in this strain. This revised version was published online in July 2006 with corrections to the Cover Date.