Effect of high-intensity irradiation from dental photopolymerization on the isolated and superfused vertebrate retina.

BACKGROUND: Light or electromagnetic radiation may damage the neurosensory retina during irradiation of photopolymerizing resinous materials. Direct and indirect effects of irradiation emitted from polymerisation curing light may represent a severe risk factor for the eyes and the skin of the lamp operators, as well as for the patient's oral mucosa. METHODS: Bovine superfused retinas were used to record their light-evoked electroretinogram (ERG) as ex vivo ERGs. Both the a- and the b-waves were used as indicators for retinal damage on the functional level. The isolated retinas were routinely superfused with a standard nutrient solution under normoglycemic conditions (5 mM D-glucose). The change in the a- and b-wave amplitude and implicit time, caused by low and high intensity irradiation, was calculated and followed over time. RESULTS: From the results, it can be deduced that the irradiation from LED high-power lamps affects severely the normal physiological function of the bovine retina. Irradiations of 1,200 lx irreversibly damaged the physiological response. In part, this may be reversible at lower intensities, but curing without using the appropriate filter will bleach the retinal rhodopsin to a large extent within 20 to 40 s of standard application times. CONCLUSION: Constant exposure to intense ambient irradiation affects phototransduction (a-wave) as well as transretinal signalling. The proper use of the UV- and blue-light filtering device is highly recommended, and may prevent acute and long lasting damage of the neurosensory retina.

MfERG responses to long-duration white stimuli in glaucoma patients.

The intent of our study was to evaluate whether the response to a long-duration white stimulus in the multifocal electroretinogram (mfERG) is sufficiently sensitive to detect early retinal dysfunction in glaucoma. On-off mfERGs were recorded from 15 NTG and 15 HTG patients and compared with 14 control subjects. Recording parameters were the following: LED stimulus screen (RETIscan™), 100-ms stimulus duration, 200-ms stimulus interval, 11-min total recording time, stimulus matrix of 61 elements, frame rate: 70 Hz, Lmax: 180 cd/m(2), Lmin: 0 cd/m(2), and filter setting: 1-200 Hz. The second negative response following stimulus onset (N2-on), as well as following stimulus offset (N2-off), was analyzed as an overall response and in quadrants, as well as in 4 small central and four adjoining peripheral areas per quadrant. The latency of the N2-on was significantly delayed in HTG in all response averages tested, while in NTG this was only seen in the overall response and in the small central response averages (P < 0.05). The most sensitive measure in HTG was the latency of the N2-on of the small peripheral response average of the superior temporal quadrant with an area under the ROC curve of 0.881. For NTG, the most representative measure was the latency of the N2-on of the small central response average of the inferior nasal quadrant with an area under the ROC curve of 0.793. Our results showed that in stimulation with long-duration flashes, the second negative response following the on response, representative of the early PhNR, is affected in glaucoma where N2-on showed a latency delay in POAG patients. The latency delay of the N2-on was more prominent for HTG than for NTG.

Optimising the structure and function of the adult P23H-3 retina by light management in the juvenile and adult.

This study tests the potential of light restriction to optimise retinal structure and function in adulthood, using the P23H-3 rhodopsin-mutant transgenic rat as a model. P23H-3 rats were reared in scotopic (5 lux) or mesopic (40-60 lux) cyclic (12 h/12 h light/dark) light. A further 2 groups were reared in one of these light conditions to P(postnatal day)30, and then were transferred to the other condition. Retinae were examined at P30-365. Rod and cone function were assessed by the dark-adapted flash electroretinogram. The rate of photoreceptor death was assessed with the TUNEL technique, and photoreceptor survival by the thickness of the outer nuclear layer (ONL). Photoreceptor structural changes were assessed by immunohistochemistry. Mesopic rearing severely reduced the number, function and outer segment (OS) length of photoreceptors. Light restriction in the adult (achieved by moving mesopic-reared animals to scotopic conditions at P30) slowed photoreceptor death, induced recovery of the ERG and of OS length in survivors, resulting in an adult retina that matched the scotopic-reared in function, photoreceptor survival (stability) and structure. Conversely, light exposure in the adult (achieved by moving scotopic-reared animals to mesopic conditions at P30) accelerated photoreceptor death, shortened OSs and reduced the ERG, resulting in a retina that was as damaged and dysfunctional as a mesopic-reared retina, and showed greater photoreceptor instability. Present observations suggest, that the stability and function of adult photoreceptors are determined by both early and adult ambient light experience. Light restriction in the adult was effective in inducing the self-repair of photoreceptors, and the recovery of their function and stability. Light restriction in the juvenile (before P30) improved early photoreceptor survival but made adult photoreceptors vulnerable to brighter light experienced in adulthood. For comparable human dystrophies, these results suggest that light restriction begun after retinal maturation may be effective in optimising the structure, function and stability of the adult retina.

Calpains are activated by light but their inhibition has no neuroprotective effect against light-damage.

Calpain had been shown to be highly activated at one day after exposure to the damaging light (Perche et al. (2007)Caspase-dependent apoptosis in light-induced retinal degeneration. Invest Ophthalmol Vis Sci 48:2753-2759.), suggesting that they might play a critical role in photoreceptor apoptosis induced by light. Therefore in the present study we investigate the role of calpain in light-induced photoreceptor cell death. In a first set of experiments, untreated albino Wistar rats were sacrificed at 0, 2, 4, 6, 12, 24 h of light exposure and at one day after the light was turned off (D1) to measure retinal calpain activity and to study calpain expression. In a second set of experiments, after control electroretinograms (ERGs), rats were uninjected or injected intravitreally with DMSO or the calpain inhibitor Mu-Phe-hPhe-FMK, before being exposed to the damaging light for 24 h. ERGs were then recorded at one day (D1) and fifteen days (D15) after the end of light exposure. Rats were sacrificed at D1 for apoptotic cell detection or D15 for histological analysis (ONL thickness). Calpain activity and expression significantly increased in Untreated retinas, from 0 h to D1. DMSO has no effect on calpain activity. Mu-Phe-hPhe-FMK significantly inhibited retinal calpain activity by 85% at 2 h of light exposure and still 48% at D1. However, Mu-Phe-hPhe-FMK has no effect on light-induced retinal degeneration as evidence by equivalent loss of function, equivalent loss of photoreceptor cells and an equivalent number of apoptotic cells in Mu-Phe-hPhe-FMK and DMSO retinas. Therefore, calpains are up-regulated by light stress but they do not have a pivotal role in photoreceptor apoptosis.

A novel isoform of acetylcholinesterase exacerbates photoreceptors death after photic stress.

PURPOSE: To study the involvement of stress-induced acetylcholinesterase (AChE) expression in light-induced retinal damage in albino rats. METHODS: Adult albino rats were exposed for 24 hours to bright, damaging light. AChE expression was monitored by in situ hybridization, by histochemistry for AChE activity, and by immunocytochemistry. An orphan antisense agent (Monarsen; Ester Neurosciences, Ltd., Herzlia Pituach, Israel) was administered intraperitoneally to minimize light-induced AChE expression. The electroretinogram (ERG) was recorded to assess retinal function. RESULTS: Twenty-four-hour exposure to bright light caused severe reduction in the ERG responses and augmented expression of mRNA for the "read-through" variant of AChE (AChE-R) in photoreceptor inner segments (IS), bipolar cells, and ganglion cells. AChE activity increased in IS. The expressed AChE protein was a novel variant, characterized by an extended N terminus (N-AChE). Systemic administration of the orphan antisense agent, Monarsen, reduced the photic induction of mRNA for AChE-R, and of the N-AChE protein. Rats exposed to bright, damaging light and treated daily with Monarsen exhibited larger ERG responses, relatively thicker outer nuclear layer (ONL), and more ONL nuclei than did rats exposed to the same damaging light but treated daily with saline. CONCLUSIONS: The findings indicate that the photic-induced novel variant of AChE (N-AChE-R) may be causally involved with retinal light damage and suggest the use of RNA targeting for limiting such damage.

Protective effect of TEMPOL derivatives against light-induced retinal damage in rats.

PURPOSE: OT-551 (1-hydroxy-4-cyclopropanecarbonyloxy-2,2,6,6-tetramethylpiperidine hydrochloride), a TEMPOL-H (OT-674) derivative, is a new catalytic antioxidant. In the present study, the efficacy of OT-551 and OT-674 in retinal neuroprotection was tested in a model of light-induced photoreceptor degeneration. METHODS: Albino rats were intraperitoneally injected with OT-551, OT-674, or water, approximately 30 minutes before a 6-hour exposure to 2700-lux white fluorescent light. Retinal protection was evaluated histologically by measuring the thickness of the outer nuclear layer (ONL) and functionally by electroretinogram (ERG) analysis, 5 to 7 days after exposure to light. Levels of protein modification by 4-hydroxynonenal (4-HNE) and 4-hydroxyhexenal (4-HHE), which are end products of the nonenzymatic oxidation of n-6 and n-3 polyunsaturated fatty acids, respectively, were measured by Western dot blot analysis immediately after exposure to light. RESULTS: After exposure to light, water-treated animals had a 77% loss of ERG b-wave amplitudes and a 26% and 56% loss of mean ONL thickness in the inferior and superior hemispheres, respectively. Compared with water-treated rats, ERG b-wave amplitudes in light-exposed eyes were significantly higher in 25 (P < 0.05)-, 50 (P < 0.05)-, and 100 (P < 0.001)-mg/kg OT-551-treated rats. Mean ONL thickness in the superior hemisphere was significantly higher in 25 (P < 0.01)-, 50 (P < 0.01)-, and 100 (P < 0.001)-mg/kg OT-551-treated, light-exposed eyes and in 100 mg/kg (P < 0.05) OT-674-treated eyes. No decrease of ONL thickness was observed in the light-protected covered fellow eyes in any animal. Increased levels of 4-HNE- and 4-HHE-protein modifications after exposure to light in water-treated eyes were completely counteracted by 100 mg/kg OT-551. CONCLUSIONS: Systemic administration of OT-551 and OT-674 provides both functional and morphologic photoreceptor cell protection against acute light-induced damage, most likely by inhibiting lipid peroxidation. The protection by OT-551 was greater than OT-674.

Electroretinographic Assessment of Inner Retinal Signaling in the Isolated and Superfused Murine Retina.

PURPOSE: Longer-lasting electroretinographic recordings of the isolated murine retina were initially achieved by modification of a phosphate-buffered nutrient solution originally developed for the bovine retina. During experiments with a more sensitive mouse retina, apparent model-specific limitations were addressed and improvements were analyzed for their contribution to an optimized full electroretinogram (ERG). MATERIAL AND METHODS: Retinas were isolated from dark-adapted mice, transferred to a recording chamber and superfused with different solutions. Scotopic and photopic ERGs were recorded with white flashes every 3 minutes. The phosphate buffer (Sickel-medium) originally used was replaced by a carbonate-based system (Ames-medium), the pH of which was adjusted to 7.7-7.8. Moreover, addition of 0.1 mM BaCl2 was investigated to reduce b-wave contamination by the slow PIII component typically present in the murine ERG. RESULTS: B-wave amplitudes were increased by the pH-shift (pH 7.4 to pH 7.7) from 22.9 ± 1.9 µV to 37.5 ± 2.5 µV. Improved b-wave responses were also achieved by adding small amounts of Ba2+ (100 µM), which selectively suppressed slow PIII components, thereby unmasking more of the true b-wave amplitude (100.0% with vs. 22.2 ± 10.7% without Ba2+). Ames medium lacking amino acids and vitamins was unable to maintain retinal signaling, as evident in a reversible decrease of the b-wave to 31.8 ± 3.9% of its amplitude in complete Ames medium. CONCLUSIONS: Our findings provide optimized conditions for ex vivo ERGs from the murine retina and suggest that careful application of Ba2+ supports reliable isolation of b-wave responses in mice. Under our recording conditions, murine retinas show reproducible ERGs for up to six hours.

Prolonged rhodopsin phosphorylation in light-induced retinal degeneration in rat models.

PURPOSE: The effects of various light-induced stresses on the retina were examined in the retinal degenerative rat model. METHODS: Retinal morphology and electroretinograms (ERGs) were analyzed after application of light-induced stress of several intensities (650, 1300, 2500, or 5000 lux). For evaluation of rhodopsin (Rho) function, the kinetics of Rho regeneration and dephosphorylation were studied by spectrophotometric analysis and immunofluorescence labeling with antibodies specifically directed toward the phosphorylated residues (334)Ser and (338)Ser in the C terminus of Rho. Retinal cGMP concentration was determined by ELISA. Expression levels of neurotrophic factors (FGF2, brain-derived neurotrophic factor [BDNF], platelet-derived growth factor [PDGF], and ciliary neurotrophic factor [CNTF]) were evaluated quantitatively by RT-PCR. RESULTS: Light intensity-dependent deterioration of ERG responses and thinning of the retinal outer nuclear layer were observed in wild-type and Royal College of Surgeons (RCS) rat retinas. Under dark adaptation after light-induced stress, the kinetics of Rho regeneration were not different between wild-type and RCS rat retinas. Rho dephosphorylation at (334)Ser and (338)Ser was extremely delayed in RCS rat retinas compared with wild-type without light-induced stress, but Rho dephosphorylation at those sites became slower in both RCS and wild-type rat retinas. In terms of expression of neurotrophic factors, almost no significant changes were observed between the animals after light-induced stress. CONCLUSIONS: The present study indicates that light-induced stress causes intensity-dependent deterioration in retinal function and morphology in wild-type and RCS rat retinas. Disruption of the phototransduction cascade resulting from slower kinetics of Rho dephosphorylation appears to be involved in retinal degeneration.

Retinal light damage: structural and functional effects of the antioxidant glutathione peroxidase-1.

PURPOSE: The role of the antioxidant enzyme glutathione peroxidase-1 (GPx1) in protecting the retina against photo-oxidative damage was investigated in GPx1-deficient and wild-type mice. METHOD: Albino GPx1-deficient and age-matched wild-type mice were examined. Baseline electroretinograms (ERGs) were recorded. Thereafter, mice were exposed to intense light for 12 hours. After a 24-hour recovery in darkness, post-light-insult ERGs were recorded and compared with baseline. Structural effects of light insult were evaluated by retinal histology. Antioxidant expression was investigated by quantitative reverse transcription-PCR (qRT-PCR). RESULTS: Light insult significantly affected ERG responses, with reduced a- and b-wave amplitudes. Structurally, photoreceptor layers were predominantly affected. As expected, GPx1 expression was negligible in GPx1-deficient mice but was upregulated in wild-type mice in response to light insult. Similarly, hemeoxygenase-1 and thioredoxin-1 expression increased significantly in wild-type retinas after light exposure. Catalase, GPx isoforms (GPx2 to -4), peroxiredoxin-6, glutaredoxin-1, and thioredoxin-2 expression was unaffected by GPx1 deficiency and light insult, whereas significant increases in glutaredoxin-2 occurred in non-light-exposed (baseline) GPx1-deficient retinas. Compared with baseline wild-type retinas, lipid peroxidation (TBARS assay), an indicator of oxidative stress, was elevated in baseline GPx1-deficient retinas. Unexpectedly, the light insult induced diminution of retinal function, in terms of ERG amplitude, and structural damage was significantly greater in wild-type than in with GPx1-deficient retinas. CONCLUSIONS: The data showing increased oxidative damage in baseline GPx-deficient retina give rise to the hypothesis that increased oxidative stress provides a "preconditioning" environment in which protective mechanisms paradoxically render GPx1-deficient retinas less vulnerable to light-induced oxidative damage. This study identified glutaredoxin-2 as a potential candidate.

Analysis of the human a-wave ERG component.

The a-wave is one of the main issues of research in the field of ocular electrophysiology, since it is strictly connected with early photoreceptoral activities. The present study proposes mathematical methods that analyse this component in human subjects, and supports experimental evidence relating to possible correlations among the responses of photoreceptoral units under a light stimulus. The investigation is organized in two parts: the first part concerns the onset and the initial slope, up to the first minimum (about 10-15 ms), the second part deals with the main portion of the wave, up to about 30 ms. In both cases, the a-waves, recorded at various levels of luminance, have been fitted with a set of appropriate functions representing possible models of physiological behaviour which would take place in the early stages of phototransduction. The statistical nature of the underlying processes is also discussed. The results indicate that correlations occur in the early stages, whereas random processes are set up later.

The Shift of ERG B-Wave Induced by Hours' Dark Exposure in Rodents.

PURPOSE: Dark adaptation can induce a rapid functional shift in the retina, and after that, the retinal function is believed to remain stable during the continuous dark exposure. However, we found that electroretinograms (ERG) b-waves gradually shifted during 24 hours' dark exposure in rodents. Detailed experiments were designed to explore this non-classical dark adaptation. METHODS: In vivo ERG recording in adult and developing rodents after light manipulations. RESULTS: We revealed a five-fold decrease in ERG b-waves in adult rats that were dark exposed for 24 hours. The ERG b-waves significantly increased within the first hour's dark exposure, but after that decreased continuously and finally attained steady state after 1 day's dark exposure. After 3 repetitive, 10 minutes' light exposure, the dark exposed rats fully recovered. This recovery effect was eye-specific, and light exposure to one eye could not restore the ERGs in the non-exposed eye. The prolonged dark exposure-induced functional shift was also reflected in the down-regulation on the amplitude of intensity-ERG response curve, but the dynamic range of the responsive light intensity remained largely stable. Furthermore, the ERG b-wave shifts occurred in and beyond classical critical period, and in both rats and mice. Importantly, when ERG b-wave greatly shifted, the amplitude of ERG a-wave did not change significantly after the prolonged dark exposure. CONCLUSIONS: This rapid age-independent ERG change demonstrates a generally existing functional shift in the retina, which is at the entry level of visual system.

Acid-sensing ion channel 2 is important for retinal function and protects against light-induced retinal degeneration.

pH variations in the retina are thought to be involved in the fine-tuning of visual perception. We show that both photoreceptors and neurons of the mouse retina express the H+-gated cation channel subunits acid-sensing ion channel 2a (ASIC2a) and ASIC2b. Inactivation of the ASIC2 gene in mice leads to an increase in the rod electroretinogram a- and b-waves and thus to an enhanced gain of visual transduction. ASIC2 knock-out mice are also more sensitive to light-induced retinal degeneration. We suggest that ASIC2 is a negative modulator of rod phototransduction, and that functional ASIC2 channels are beneficial for the maintenance of retinal integrity.

Visual responses in teleosts. Electroretinograms, eye movements, and circadian rhythms.

We have recorded ocular potentials in response to brief flashes of light from two teleosts, the white perch (Roccus americana) and the green sunfish (Lepomis cyanellus). The animals were respired and maintained in an alert state for up to 2 d. Responses were recorded with corneal and transcleral electrodes. The responses of green sunfish were composed of electroretinogram (ERG) and eye movement potentials, whereas the responses in white perch contained only the ERG. Injection of curare abolished the sunfish eye movement potentials, unmasking the ERG. Observation under infrared illumination established a direct relationship between eye movements and the fast potentials which could be abolished by curare. We found no evidence of circadian changes in the amplitude of the ERG b-wave of either species. However, our results combined with those of a previous study of sunfish ocular potentials (Dearry, A., and B. Barlow, Jr. 1987. J. Gen. Physiol. 89: 745-770) suggest that the sunfish visual system exhibits rhythmic changes in oculomotor responses, which appear to be controlled by a circadian oscillator.

Ultraviolet- and short-wavelength cone contributions alter the early components of the ERG of young zebrafish.

The electroretinogram (ERG) is a commonly used measure to examine retinal processing in both basic and clinical research. The purpose of this study was to determine the retinal mechanisms responsible for the developmental differences found in the zebrafish ERG waveform. The ERG of young zebrafish possesses a voltage-negative response to ultraviolet- and short-wavelength stimuli, but not to middle- and long-wavelength stimuli; the ERG of adult zebrafish does not possess this response component. ERGs were obtained from young zebrafish before and after the introduction of either aspartate, or a combination of APB (DL-2-amino-4-phosphonobutyric acid) and PDA (cis-2,3-piperidinedicarboxylic acid) in order to suppress the responses of various types of retinal neurons. Log irradiance versus response amplitude functions of the ERG response to 200-ms stimuli of various wavelengths at various times following stimulus onset (70 and 120 ms) was derived as well as spectral sensitivity. Aspartate eliminated all voltage-positive responses regardless of stimulus wavelength; irradiance-response functions following aspartate were similar to the early responses of young control fish to ultraviolet- and short-wavelength stimuli. APB + PDA produced similar but not identical results as aspartate, suggesting that the combination of these agents does not completely eliminate all post-receptoral contributions to the ERG. Spectral sensitivity functions derived from aspartate-exposed subjects at various time measurements were dominated by contributions from ultraviolet- and short-wavelength-sensitive cone types. These wavelength-dependent ERG responses are similar to those found in humans with enhanced S-cone syndrome. Finally, ERG waveform differences across stimulus wavelength suggest that the circuitry of ultraviolet- and short-wavelength cone types is different to that of middle- and long-wavelength cone types in young zebrafish.

Light induces peroxidation in retina by activating prostaglandin G/H synthase.

Prostaglandin G/H synthase (PGHS) has been shown to generate peroxides to a significant extent in the retina and absorbs light at the lower end of the visible spectrum. We postulated that PGHS could be an important initial source of peroxidation in the retina exposed to light, which would in turn alter retinal function. Exposure of pig eyes (in vivo) to light (350 fc/3770 lx) caused after 3 h a 50% increase and by 5 h a 30% decrease in a- and b-wave amplitudes of the electroretinogram (ERG) which were comparable at 380-650 nm and 380-440 nm but were not observed at wavelengths > 450 nm. These effects of light were prevented by free radical scavengers (dimethylthiourea and high-dose allopurinol) and PGHS inhibitors (naproxen and diclofenac), but stable analogs of prostaglandins did not affect the ERG. Both increases and subsequent decreases in ERG wave amplitudes following light exposure in vivo were associated with increases in retinal prostaglandin and malondialdehyde (peroxidation product) levels, which were inhibited by the nonselective PGHS blockers, naproxen and diclofenac. Similar observations were made in vitro on isolated porcine eyecups as well as on retinal membranes exposed to light (250 fc/ 2700 lx) 380-650 nm and 380-440 nm but not at > 500 nm. Both PGHS-1 and PGHS-2 contributed equivalently to light-induced prostaglandin synthesis, as shown after selective PGHS-2 blockers, but mRNA expression of PGHS-1 and 2 was not affected by light. Finally, light stimulated activities of pure PGHS-1 and PGHS-2 isozymes, and these were also shown to produce superoxide radical (detected with fluorogenic spin trap, proxyl fluorescamine). Taken together, data suggest that PGHS- (1 and 2) is activated by short wavelength visible light, and in the retina is an important source of reactive oxygen species which in turn alter retinal electrophysiological function. PGHS thus seems a likely chromophore in setting forth photic-induced retinal injury. Findings provide an explanation for increased sensitivity of the retina to visible light predominantly at the far blue range of its spectrum.

Stray light-induced multifocal electroretinograms.

PURPOSE: To evaluate the characteristics of stray light-induced response in multifocal ERG (mfERG) elicited by the stimulus falling on the disc. METHODS: A patient with an enlarged optic disc (4 x 4 disc diameters of disc of normal fellow eye) and four normal volunteers served as subjects. The mfERGs elicited by different stimulus intensities (0.67-4.67 cd-sec/m(2)) were recorded from the patient, and the mfERGs obtained with stimuli on the enlarged optic disc. For comparison, full-field pseudorandom ERGs (ffprERGs) were also recorded in all subjects. The first-order kernels (K1) and the second-order kernels (K2.1) were analyzed. RESULTS: A small and delayed K1 was recorded on the enlarged disc, but K2.1 was flat on the disc at all intensities. The implicit time of K1 at lower intensities was longer than at higher intensities. ffprERGs at very low intensities in the patient and normal subjects were similar to the mfERG on the disc (delayed K1 associated with flat K2.1). CONCLUSIONS: The responses elicited by stimulating the disc were delayed in K1 and flat in K2.1. Because similar ffprERGs were observed at very low intensities, it is likely that an optic disc with high reflectance scattered the stimulus light to create a weak full-field stimulus. Thus, care must be taken when focal lesions are investigated with mfERGs.

Regional variations in local contributions to the primate photopic flash ERG: revealed using the slow-sequence mfERG.

PURPOSE: To determine the variations with eccentricity of the primate photopic ERG and to separate contributions by different retinal cells by using intravitreal pharmacologic agents. METHODS: Slow-sequence multifocal (mf)ERGs were obtained from 19 anesthetized adult rhesus monkeys and 5 normal human subjects. Recordings in monkeys were obtained before and after injections of tetrodotoxin citrate (TTX) to block sodium-dependent spiking; TTX+N-methyl-D-aspartic acid (NMDA)+picrotoxin (PTX) or gamma-aminobutyric acid (GABA) to block all inner retinal activity; L-2 amino-4-phosphonobutyric acid (APB) to block the On-pathway; and cis-2, 3 piperidine dicarboxylic acid (PDA) to block the Off-pathway and the otherwise unblocked inner retinal activity. The stimulus consisted of 103 equal-sized hexagons within 17 degrees of the fovea; every 200 ms (15 frames), each hexagon had a 50% chance of remaining at 20 cd/m(2) or increasing briefly to 4.7 cd-s/m(2). Oscillatory potentials (OPs; 90-300 Hz) were extracted. RESULTS: The slow-sequence mfERG summed over the stimulated area looked similar to a standard photopic, full-field ERG, with a- and b-waves and OPs. OPs in the foveal and temporal retina were larger than in the nasal retina. This nasotemporal asymmetry was removed by TTX, and the OPs were eliminated, either by blocking inner retina activity or by blocking the On-pathway. The summed mfERG waveform, including OPs, was shaped mainly by the more peripheral retinal regions. The foveal b-wave peak occurred about 5 to 6 ms later than in the periphery, with the depolarizing peak of the On-pathway/bipolar contribution occurring earlier than the depolarizing peak of the Off contribution at all eccentricities. The a-wave was composed of a small photoreceptor contribution and postreceptoral portion originating from hyperpolarizing neurons. CONCLUSIONS: The variations in the primate photopic ERG with eccentricity are due to spike-driven oscillatory activity that is more prominent in central and temporal retina than in nasal retina and to the slower timing of all responses in the central, compared with the peripheral, retina. The full-field, photopic ERG most closely resembles the mfERG responses to stimulation of peripheral regions.

The effects of forward light scattering on the multifocal electroretinogram.

PURPOSE: To study the effects of forward light scattering on the multifocal electroretinogram (mfERG). METHODS: Thirty young normal subjects were recruited for this study. The mfERG was measured under five conditions. (1) no light scattering (stimulus contrast 93%), (2) mild light scattering (stimulus contrast 80%), (3) moderate light scattering (stimulus contrast 50%), (4) no light scattering (stimulus contrast 80%), and (5) no light scattering (stimulus contrast 50%). RESULTS: The amplitudes of N1 and P1 from the central retina did not change significantly, but the amplitudes of N1 and P1 in the mid peripheral retina increased with the increase of forward light scattering. By comparing conditions 1, 4 and 5, it was shown that the amplitudes of N1 and P1 decreased at all eccentricities when stimulus contrast reduced from 93% to 50%. CONCLUSIONS: This study suggests that the topography and waveform of the mfERG could be affected by forward light scattering.

Specific features of the electroretinogram of vertebrates induced by X-rays.

The net electroretinograms of dark-adapted retinas of the common frog in situ were investigated on an automated experimental system with programmed control and electronic differentiation of biopotentials with respect to the first and second derivatives. It was demonstrated that X-rays elicit an electroretinogram consisting of two components, provisionally called the first and second X-ray reactions (X-1 and X-2), which differ with respect to their parameters from electroretinograms elicited under the same conditions by red and blue light. The administration of sodium azide, sodium nitrate, monoiodo-acetate and other substances alter the X-1 and X-2 as well as the photo-induced ERGs in different ways; this indicates their relative independence and different mechanisms of the occurrence and passing of excitation across the structures of the retina, and makes it possible to partially isolate these for individual study. Thus, the assertion of a number of investigators regarding the absence of specific features in the X-ray induced electroretinograms becomes problematical. The discovery of X-ray-specific reactions in the retina makes it possible to hope that the radiological phosphene (the X-ray phosphene) may serve as a test for the determination of the individual radiational excitability of the central nervous system.

[The effect of prolonged exposure to UV radiation on the state of the ocular media and on the parameters of the electroretinogram in the rabbit]. / Vliianie dlitel'nogo vozdeistviia UF-izlucheniia na sostoianie glaznykh sred i parametry élektroretinogrammy krolika.

Rabbits were exposed to vertically directed UV-B radiation (280-320 nm) 5 days a week during 10 months with daily dose 6.5 J/m2 (biological effective daily dose 0.83 J/m2). Within the first week expressed photokeratoconjunctivitis was observed, but to the end of third week state of cornea and conjunctiva became practically normal. Transparency of intra-eye structures was unchanged, functional activity of retina underwent undulatory alterations. Amplitude changes of a- and b-waves of electroretinogram reached 30% of control values during the first, were negligible within the second, and exceed control by 15-20% between 8 and 10-th months of exposure. Critical frequency of flashing was unchanged.