Effects of the protein tyrosine kinase inhibitor genistein and taurine on retinal function in isolated superfused retina

Background Genistein has the potential to act as an intraocular antiangiogenic agent. Its therapeutical use, however, is limited by toxic side effects on the retina. This study was designed to evaluate the simultaneous use of taurine as a neuroprotective drug. Methods Bovine retinas were isolated and perfused with an oxygen-preincubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal electrical potential using Ag/AgCl electrodes. At stable ERG amplitudes, genistein at concentrations of 11, 37, and 150 μM was added to the nutrient solution for 45 min, in the absence or presence of taurine (3 mM). Thereafter, the retina was reperfused with the nutrient solution for another 100 min. The percentage of b-wave reduction during genistein and genistein/taurine application was calculated. Results The b-wave amplitude was reduced by a smaller amount during the application of genistein (11 and 37 μM) in the presence of taurine compared with genistein alone. For both, genistein/taurine and genistein alone the b-wave recovered completely during the wash-out of the drugs. However, during the application of the highest tested concentration of genistein (150 μM), taurine did not protect completely, leading to an irreversible b-wave reduction. Conclusions The adjuvant use of taurine reduces the genistein-induced retinal toxicity to a certain degree. However, the protective effect of taurine is limited and there is only a narrow therapeutic index for a combined intravitreal administration of genistein in coapplication with taurine to inhibit pathological ocular neovascularization. Dedicated to the late Prof. Dr. Werner Sickel. He passed away on December 18th, 2004     

Effects of bevacizumab on retinal function in isolated vertebrate retina

BACKGROUND: Bevacizumab (Avastin) is a recombinant protein that targets vascular endothelial growth factor (VEGF). In vitro, bevacizumab inhibits VEGF induced cell proliferation and tissue factor production. Abnormal angiogenesis involving VEGF is a central event during the development of choroidal neovascularisation (CNV). The present study was designed to evaluate the short term toxic effects of bevacizumab on retinal function for a therapeutic intraocular application. METHODS: Isolated bovine retinas were perfused with an oxygen pre-incubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using silver/silver chloride electrodes. Bevacizumab was added in different concentrations to the nutrient solution for 45 minutes. Thereafter the retina was reperfused for 60 minutes with normal nutrient solution. The percentage of a-wave and b-wave reduction during the application of bevacizumab was calculated and compared to control recordings. RESULTS: During the application of three different concentrations of bevacizumab (0.08 mg/ml, 0.25 mg/ml, 0.8 mg/ml) no significant reduction of the a-wave and b-wave amplitude was observed. During the washout, the ERG amplitudes were unchanged. CONCLUSION: The present study suggests that an intraocular application of 0.25 mg/ml bevacizumab for the treatment of CNV is reasonable. No significant short term effects of bevacizumab on retinal function were detected, but long term effects cannot be excluded.     

The retinal tolerance to bevacizumab in co-application with a recombinant tissue plasminogen activator

AIM: To investigate the retinal toxicity of bevacizumab in co-application with a commercially available recombinant tissue plasminogen activator (rt-PA), and to facilitate a new therapeutic concept in the treatment of massive subretinal haemorrhage caused by neovascular age-related macular degeneration (AMD). METHODS: Isolated bovine retinas were perfused with an oxygen-preincubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using Ag/AgCl electrodes. Bevacizumab (0.25 mg/ml) and rt-PA (20 microg/ml) were added to the nutrient solution for 45 min. Thereafter, the retina was reperfused for 60 min with normal nutrient solution. Similarly, the effects of rt-PA (20 microg/ml, 60 microg/ml and 200 mug/ml) on the a- and b-wave amplitudes were investigated. The percentages of a- and b-wave reduction during application and at washout were calculated. RESULTS: During application of bevacizumab (0.25 mg/ml) in co-application with 20 microg/ml (rt-PA), the ERG amplitudes remained stable. The concentrations of rt-PA alone (20 microg/ml and 60 microg/ml) did not induce significant reduction of the b-wave amplitude. In addition, 20 microg/ml rt-PA did not alter the a-wave amplitude. However, 60 microg/ml rt-PA caused a slight but significant reduction of the a-wave amplitude. A full recovery was detected for both concentrations during the washout. At the highest tested concentration of 200 microg/ml rt-PA, a significant reduction of the a- and b-wave amplitudes was provoked during the exposure. The reduction of ERG amplitudes remained irreversible during the washout. CONCLUSION: The present study suggests that a subretinal injection of 20 microg/ml rt-PA in co-application with bevacizumab (0.25 mg/ml) for the treatment of massive subretinal haemorrhage seems possible. This is a safety study. Therefore, we did not test the clinical effectiveness of this combined treatment.     

Effects of phosphodiesterase type 5 inhibitor sildenafil on retinal function in isolated superfused retina.

After the oral ingestion of sildenafil, visual abnormalities have been reported constantly. The mechanism of these adverse events has been presumed to be a result of the interaction of sildenafil with the retinal phosphodiesterase (PDE) type 6. To investigate the physiological basis of the effects of sildenafil on retinal function, bovine retinas were isolated and perfused with an oxygen pre-equilibrated standard solution. The electroretinogram (ERG) was recorded as a transretinal potential using silver/silver-chloride electrodes. After reaching stable ERG amplitudes, sildenafil was added to the nurient solution at different concentrations, and its effect on the a- and b-wave amplitude was studied separately. The 0.1 microM and higher concentrations of sildenafil reduced the b-wave amplitude, while a reduction of the a-wave amplitude was observed at an elevated threshold of 0.3 microM. The changes of the ERG amplitudes were fully reversible for the b-wave at a concentration of 0.1 microM and for the a-wave at 0.3 microM sildenafil. At higher concentrations, sildenafil was found to be only partially reversible within recovery time. In conclusion, besides an inhibitory influence on photoreceptors, sildenafil performs additional effects on the postsynaptic neuronal network. Higher concentrations of sildenafil were found to have a potential for retinal degeneration, suggesting that further trials should be designed to evaluate the long-term effects of sildenafil. The physiological consequences of an abuse or long-term, daily use of sildenafil are not clear.     

The effects of the phosphodiesterase type V inhibitor sildenafil on human and bovine retinal function in vitro

Background After the ingestion of sildenafil (Viagra), visual adverse events have been reported, possibly caused by an inhibition of the phototransduction cascade by sildenafil via phosphodiesterase (PDE 6). Therefore, we investigated the effects of sildenafil on photoreceptors and postsynaptic neurons of human and bovine retinas using the isolated superfused vertebrate retina technique. Methods Human and bovine retina preparations were perfused with an oxygen preequilibrated standard solution. The electroretinogram (ERG) was recorded using Ag/AgCl electrodes. After recording stable ERG amplitudes, sildenafil was added to the solution for 45 min. Thereupon, the preparations were reperfused with standard solution for 240 min. Results Following the application of sildenafil (3 μMol/l), the b-wave amplitude of bovine and human preparations was reduced continuously and disappeared completely. After reperfusion with the standard solution for 4 h, the b-wave amplitude did not recover completely. Using the same sildenafil concentration (3 μMol/l), the a-wave amplitude of the human retina was not totally abolished, but reduced to 21% of the initial amplitude and remained reduced at washout. For all retinal preparations, the implicit time of the ERG amplitudes remained significantly extended at the end of the washout. Conclusions Strong similarities were detected in the drug-induced changes of the ERG when comparing human and bovine retinas. The results suggest that sildenafil impairs retinal function at not only the level of the photoreceptors, but it also affects the neuronal network of the inner retina at concentrations of approximately 30-fold higher than at therapeutic plasma concentrations. Dedicated to the late Prof. Dr. Werner Sickel, who passed away on 18th December 2004.     

Investigating retinal toxicity of tempol in a model of isolated and perfused bovine retina

Purpose

Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxyl) is a membrane-permeable superoxide dismutase and potentially neuroprotective substance. This study evaluates the retinal tolerance of 0.5 mM, 1 mM, 2 mM, and 5 mM tempol measured by the electroretinogram (ERG) of an isolated and perfused retina whole mount.

Methods

For functionality testing, bovine retinas were prepared and perfused with an oxygen-saturated standard solution, and the ERG was recorded until stable b-wave amplitudes were reached. Tempol concentrations of 0.5 mM, 1 mM, 2 mM, and 5 mM were tested for 45 minutes. To investigate the effects on photoreceptor function, 1 mM aspartate was added to suppress the b-wave and obtain isolated a-waves. ERG amplitudes were monitored for 100 minutes.

Results

While no toxic effects for concentrations of 0.5 mM and 1 mM tempol could be detected, concentrations of 2 mM tempol and higher caused statistically significant negative effects on the b-wave amplitude (?38 %, p?=?0.02 for 2 mM; ?54 %, p?= 0.02 for 5 mM). The a-wave amplitude remained stable even at higher concentrations.

Conclusions

Although the photoreceptors seem to have a tolerance to high concentrations of tempol, higher intravitreal concentrations than 1 mM should be considered critical.     

Electrophysiological effects of Brilliant Blue G in the model of the isolated perfused vertebrate retina

Background To facilitate epiretinal or inner limiting membrane peeling dyes like Indocyanine Green (ICG) as well as Trypan Blue (TB) were used so far. However, toxic effects on the retina were described for both dyes. The aim of our study was to investigate the retinal tolerance to the new dye Brilliant Blue G (BBG), which implies a possibly more favorable biocompatibility. Methods Bovine retina preparations were perfused with an oxygen preequilibrated standard solution. The electroretinogram (ERG) was recorded using Ag/AgCl-electrodes. After recording stable b-wave amplitudes, Brilliant Blue G (BBG) was applied epiretinally for 10 s, 15 s, 30 s, 60 s and 120 s at a concentration of 0.25 mg/ml, which was recently proposed for vitreoretinal surgery. To disclose the effects of BBG on photoreceptor function two test series at the same concentration were performed to evaluate the impact of BBG on the a-wave amplitude. Aspartate at a concentration of 1 mM was added to the nutrient solution to obtain stable a-wave amplitudes. Thereafter, BBG was epiretinally applied for 30 s or 60 s. The recovery of the ERG-amplitudes was followed up for 115 min. Results Reductions of the a- and b-wave amplitude were found directly after exposure with BBG in each test series, but the effects on the electroretinogram after application of BBG were rapidly and completely reversible within the recovery time for all exposure times. No differences were found between the ERG-amplitudes before and after dye application at the end of the washout. Conclusions BBG seems to be an alternative vital staining dye with a good biocompatibility. Comparing the effects with Indocyanine Green or Trypan Blue in the model of the isolated perfused vertebrate retina BBG exhibits a more favorable safety profile.     

Effects of daunorubicin and CD95L on retinal function in superfused vertebrate retina.

Alternative treatments of proliferative vitreoretinopathy (PVR) are needed. The intravitreal application of daunorubicin combined with CD95 ligand (CD95L) could provide a new therapeutic strategy. The effects of this application on bovine retinal function were investigated. Bovine retina preparations were perfused with a standard solution preequilibrated with oxygen. The b-wave and, after the addition of aspartate, the photoreceptor potential P III of the electroretinogram (ERG) were recorded using Ag/AgCl electrodes. Stable ERG amplitudes were recorded, then daunorubicin was added to the solution for 45 minutes, also with the addition of CD95L antibody. Subsequently, the preparation was reperfused with the standard solution for 100 minutes, to allow for recovery. The reduction in b-wave amplitude was reversible and not significantly changed by the addition of 0.25 microg/mL CD95L antibody to 13 microM of daunorubicin. The reduction of the b-wave amplitude was significantly changed and only partly reversible within the recovery time using 40 microM and 80 microM of daunorubicin. The photoreceptor potential P III amplitude was not significantly changed for up to 80 microM of daunorubicin. The ERG showed toxic effects of daunorubicin above a concentration of 13 microM used therapeutically in humans. The combination with CD95L did not increase retinal toxicity. It is, therefore, concluded that daunorubicin may be applied intraocularly, combined with CD95L, without interfering with retinal function.     

Effects of patent blue on human retinal function

Background Dye solutions for intraoperative staining of epiretinal membranes and the internal limiting membrane improve the visualisation of these thin structures and facilitate their removal. Lately, the application of patent blue for staining of the internal limiting membrane has been proposed as an alternative to the standard procedures during macular hole surgery. In the present study we investigated the effects of patent blue 0.48% on human retinal function.Methods An isolated human retina preparation was perfused with a standard solution and the electroretinogram (ERG) was recorded repeatedly. After recording of stable ERG amplitudes the nutrient solution was substituted by a commercially available patent blue solution. The duration of retinal exposure to the dye solution was varied between 15 s and 4 min. Thereupon, the preparation was reperfused with standard solution for 2 h. The percentage of b-wave reduction after exposition was calculated.Results No effects on the human ERG were seen after 15 and 30 s of dye application. Reversible reductions of the b-wave amplitude were found for an exposure period of 60 and 120 s, respectively. After 4 min of patent blue application a persistant b-wave amplitude reduction by 40% was found.Conclusions Patent blue affects human retinal function when applied for at least 1 min. However, no irreversible effects on the human ERG were seen even after 2 min of retinal exposure to patent blue. Thus, toxic effects on retinal function after intraoperative short-term application of patent blue 0.48% appear unlikely to occur.Presented in part during the Annual Congress of the German Ophthalmological Society (DOG) in Berlin, 2004     

Hyperosmolarity and electroretinogram (ERG) potentials in isolated rat retinas: possible implications in diabetic models

In this report, the effects of increases in the osmolarity of media superfusing isolated rat retinas on the a-wave, b-wave and oscillatory potentials of the electroretinogram (ERG) were examined. Osmolarity of the media was raised from 310 milliosmoles (control) to 340 and 370 milliosmoles by addition of NaCl or sucrose. Increases in osmolarity led to rapid decreases in the amplitudes of the b-wave and oscillatory potentials with little change in the amplitude of the a-wave. Excellent recovery of the ERG potentials was observed when control conditions were restored. The implications of these effects of an hyperosomotic load on ERG potentials in vitro are discussed with regard to a possible role of this load in models of experimental diabetes.     

玻璃体出血对视网膜损伤的电生理研究

通过对家兔玻璃体出血模型的视网膜电镜观察，结果表明，出血后７天，ａ，ｂ波幅显著下降，２８天时仍有明显改变，与病理改变相一致，且ａ波幅下降的幅度大于ｂ波，对其意义进行了讨论。     

Effects of hypoxemia on the a- and b-waves of the electroretinogram in the cat retina

PURPOSE: Slow components of the electroretinogram (ERG) are sensitive to even mild hypoxemia (60 < P(a)O(2) < 100 mm Hg) in the cat eye. However, the electrical responses of the inner retina remain unchanged until P(a)O(2) is below 40 mm Hg. In this study, the effects of hypoxemia on photoreceptors, on which both slow ERG components and inner retinal activity depend, were examined by recording the a-wave of the ERG. METHODS: 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-minute intervals during hypoxemic episodes lasting 15 minutes to 2 hours. RESULTS: The cat a-wave was well described by the Lamb and Pugh a-wave model during normoxia and hypoxemia. During mild hypoxemia (P(a)O(2) of 50-60 mm Hg), small changes in a-wave amplitude were detected but did not become greater during severe hypoxemia. The mean decrease in the a-wave amplitude during severe hypoxemia (P(a)O(2) of 20-30 mm Hg) was 8.9% from the mean amplitude during air breathing. The effects of hypoxemia were more severe on the b-wave amplitude. The mean decrease in the b-wave was 35% at P(a)O(2) of 20-30 mm Hg. CONCLUSIONS: The a-wave is more resistant to severe hypoxemia than the b-wave. This implies that photoreceptor transduction works almost normally during hypoxemia and that failure of inner retinal PO(2) regulation causes the decrease in the b-wave. Previously observed changes in the amplitudes of slow ERG components during hypoxemia may result from changes in the ionic environment, rather than a failure of photoreceptor energy metabolism.     

视网膜色素上皮变性大鼠随生长发育的视网膜电图改变

背景RCS—rdy-P’大鼠随着生长发育会逐渐发生视网膜色素变性（RP）,记录其生长发育过程中的视网膜电图（ERG）改变可为该模型鼠的进一步研究奠定基础。目的观察RCS—rdy-P’大鼠视网膜发育过程中的ERG变化,研究ERG随发育的变化特点。方法采用RETI-port系统、环形角膜电极和不锈钢针状电极分别记录生后21、32、37、45、60d的RCS-rdy-P’大鼠的系列暗适应ERG,每个年龄组6只鼠。取相同时间点及数量的同种系正常的RCS-rdy-P’大鼠作为正常对照。暗适应不同时间的ERG对比采用RCS-rdy＋P’生后60d大鼠共9只,每组3只。结果在刺激光强、刺激频率、体温相同的情况下,RCS-rdy-P’大鼠ERGb波振幅与暗适应时间有关,随着暗适应时间的延长,b波振幅增加,当暗适应时间超过12h时,即使暗适应时间增加,b波振幅不再增长,说明暗适应超过12h可以得到RCS-rdy＋-P’大鼠一个较为稳定的ERG波形。与RCS—rdy＋一P’大鼠比较,RCS—rdy-P’大鼠在生后21d时ERG已出现a波、b波振幅的下降,同时隐含时明显延长,以a波改变为主。随着RCS—rdy-P’大鼠年龄增长及RP的进展,ERGa波、b波振幅进一步下降,隐含时延长,RCS—rdy-P’大鼠生后60d时,其ERG反应记录不到。对照组大鼠在21d时,ERG的a波、b波均振幅较低;生后32d时RCS—rdy-P’大鼠b波振幅增加,但隐含时缩短;到生后45d仅小幅增加,45～60d再次出现b波振幅显著增加,隐含时缩短。结论RCS—rdy一一P’大鼠随着年龄的增长发生视网膜功能的变化,其暗适应ERG改变符合RP的进展过程。     

Retinal pigment epithelial dysfunction in human immunodeficiency virus-infected patients with cytomegalovirus retinitis

OBJECTIVE: Prior clinical observations led the authors to examine electrophysiologic measures of retinal (electroretinogram [ERG]) and retinal pigment epithelial (electro-oculogram [EOG]) function in patients infected with human immunodeficiency virus (HIV) who either had or did not have cytomegalovirus (CMV) retinitis in order to determine if the ERG or EOG measures were differentially affected in CMV retinitis. DESIGN: Cross-sectional study. PARTICIPANTS: Forty-one HIV-infected patients (20 with and 21 without CMV retinopathy) were evaluated. INTERVENTION: ERGs and EOGs were recorded. Patients' fundi were evaluated by indirect ophthalmoscopy or fundus photography. MAIN OUTCOME MEASURES: The ERG a- and b-wave amplitudes and EOG light/dark amplitude ratio (L/D ratio) from the eyes of all patients were compared with values 2 standard deviations from the mean of a normal sample. The area of the retinal lesions was estimated from fundus photographs or from careful drawings made during indirect ophthalmoscopy. RESULTS: The majority of the eyes (64.5%) of the patients with CMV retinitis had subnormal L/D ratios, and most eyes (95%) of patients without CMV retinitis had normal L/D ratios. Only six eyes (four with and two without CMV retinopathy) had subnormal a-wave amplitudes, and there was no significant correlation between a-wave amplitude and the L/D ratio for patients with CMV retinitis. Most eyes (80.6%) of the patients with CMV retinitis had subnormal b-wave amplitudes, but there was no significant correlation between b-wave amplitude and L/D ratio in the patients with CMV retinitis. In three patients with CMV retinitis selected to exemplify the range of effects on the ERG and EOG, the b-wave amplitude loss was roughly proportional to the area of retina visibly affected in indirect ophthalmoscopy. One patient had a nonrhegmatogenous retinal detachment. CONCLUSIONS: Middle retinal function, as reflected in the b-wave amplitude, and retinal pigment epithelial function, as reflected in the L/D ratio, were both compromised in CMV retinitis, but the effect on function in the two layers of the retina appeared independent because there was no significant correlation between the L/D ratio and b-wave amplitude. The decrease in L/D ratio was not secondary to loss of photoreceptor function and probably represents a dysfunction of the retinal pigment epithelium because there was no significant correlation between a-wave amplitude, which was normal in most cases, and L/D ratio. The inner retinal pathology of CMV retinitis is visible clinically and was associated with decreases in b-wave amplitude in this and previous studies. The significant independent retinal pigment epithelial dysfunction demonstrated in this study may be an important predisposing factor to retinal detachment in CMV retinitis.     

Influence of chlorpromazine on the rabbit electroretinogram

In anesthetized albino or nonalbino rabbits, a 3 to 8 mg/kg IV injection of chlorpromazine did not affect a-wave amplitude of the electroretinogram (ERG). However, immediately after the injection of the drug, b-wave amplitude increased. The maximum increase occurred between 35 to 50 min, and the recovery time varied between 5 to 8 hr. Initial changes in the b-wave amplitude to some extent were affected by systemic changes in the blood pressure. However, the b-wave amplitude remained high for a long time after the blood pressure reached preinjection value, indicating a local effect of the drug. There was no change in a- or b-wave latencies. Although in vitro a large quantity of chlorpromazine can be localized in the melanin granules from pigmented rabbit retina, in vivo the ERG b-wave changes caused by the small intravenous dose of the drug were similar in both albino and nonalbino rabbits.     

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.     

Increased ERG a- and b-wave amplitudes in 7- to 10-year-old children resulting from prenatal lead exposure

PURPOSE: To determine the dose-response relationship between blood lead concentration ([PbB]) and scotopic ERG amplitude in 7- to 10-year-old children with lifetime lead exposure. METHODS: Full-field flash scotopic ERGs were recorded over a 4-log-unit range in 45 dark-adapted children with normal visual acuity. [PbB] was measured throughout pregnancy and postnatal development, and the subjects' [PbB] levels were grouped at each age by tertiles. RESULTS: The median [PbB] during pregnancy was, from lowest to highest tertile, 2.5 to 5.0, 7.5 to 9.0, and 14.0 to 16.5 microg/dL, and after birth was 4.0 to 8.0, 6.0 to 14.5, and 7.5 to 21.0 microg/dL. Only maternal [PbB] at 12 weeks of pregnancy showed a significant dose-response relationship with the ERG measures, so that with increasing [PbB] there were significant increases in leading-edge a-wave amplitude, peak a-wave amplitude, and b-wave amplitude and sensitivity, with no changes in implicit times. Data analyses showed that children whose mothers had [PbB] of 10.5 microg/dL or more at 12 weeks of pregnancy had relatively increased a- and b-waves. CONCLUSIONS: Lead exposure during the first trimester of pregnancy produces dose-dependent increases in scotopic a- and b-wave amplitudes in 7- to 10-year-old children. The results suggest that the increases in a- and b-wave amplitudes originate from rods; however, the increased b-wave amplitude and sensitivity may also originate in the inner retina. These alterations occurred at maternal [PbB] at or below currently accepted safe levels. These novel findings reveal that the developing retina is a sensitive target for lead and suggest that lead-exposed children be examined for possible future visual system deficits.     

Predominant loss of the photopic negative response in central retinal artery occlusion

PURPOSE: To determine how the photopic negative response (PhNR) is affected in central retinal artery occlusion (CRAO). DESIGN: Observational case series. METHODS: Seven patients with unilateral CRAO were included. Full-field scotopic and photopic electroretinograms (ERGs) including the PhNR were recorded. Each ERG amplitude in the affected eye was expressed as a percentage of amplitude of the corresponding wave in the unaffected eye. RESULTS: Mean of the PhNR amplitude was reduced to 12.3 +/- 11.7% of that of unaffected eyes whereas the cone b-wave amplitude was attenuated to only 73.4 +/- 30.4%. This reduction of the PhNR amplitude was more significant than that of other waves including the rod b-wave, maximum a-wave and b-wave, cone a-wave and b-wave, and 30 Hz flicker ERG (P <.005). CONCLUSIONS: The PhNR was severely affected in CRAO despite relative preservation of the cone b-wave, implicating massive loss of ganglion cells and their axons.     

The contributions of voltage- and time-dependent potassium conductances to the electroretinogram in rabbits.

The electroretinogram (ERG) is generated by light-induced electrical activity in retinal cells. Since potassium ions and potassium conductances play a major role in determining the membrane potential of cells, changes in these are expected to affect the amplitude and pattern of the ERG. We recorded the ERG responses and the isolated P-III waves of rabbits after intraocular injections of specific blockers for potassium channels. 4-aminopyridine (4-AP) did not cause any noticeable changes in the ERG while tetraethylammonium chloride (TEA) induced time-dependent effects. Short-term (1-2 h) effects were expressed as significant augmentation of the b-wave with little change in the a-wave. At longer periods of follow-up, the a-wave increased in amplitude while the b-wave decreased. TEA augmented the amplitude of the isolated P-III wave. These effects of TEA can be explained by TEA-induced depolarization of the photoreceptors. Cesium ions and barium ions induced substantial augmentation of the b-wave. Barium but not cesium ions reduced the isolated P-III component of the ERG probably by blocking the potassium channels in the Müller cells. The augmentation of the b-wave by both barium or cesium ions is inconsistent with the Müller cells hypothesis for the ERG b-wave.     

Facilitatory and neurotoxic effects of intravitreal ornithine on the electroretinographic responses of albino rats

The effect of an intravitreal injection of ornithine on the retina of rats was studied electroretinographically. Rats were injected intravitreally with 5 microl of 0.02, 0.25 and 0.5 M ornithine. Electroretinograms (ERGs) were recorded before, and 1, 3 and 9 days after the injection. High doses of ornithine (0.5 M) reduced while low doses (0.02 M) enhanced the ERG amplitudes. The implicit time of the a-wave was delayed at all concentrations after ornithine injection, which suggests that implicit times may be a more sensitive parameter of the ornithine effect. There were significant changes in the stimulus intensity necessary to obtain the one half of the maximum amplitude of the b-wave that may have been caused by damage of the photoreceptors and retinal pigment epithelium cells by ornithine. We conclude that the effect of ornithine on retinal function is dose dependent and can either enhance or depress the ERG amplitudes.