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Biomedical subjects

J R Brunette

Publications and source records attributed to J R Brunette.

At least 19 recordsLinked to original sources

Effects of retinal dopamine depletion on the rabbit electroretinogram.

This study evaluated the effects of intravitreal injections of 300 micrograms of 6-hydroxydopamine (6-OHDA) on electroretinogram (ERG) amplitudes and implicit response times of adult pigmented rabbits. One eye was injected intravitreally with 300 micrograms 6-OHDA and 600 micrograms ascorbic acid in a 0.3 ml 0.9% NaCl solution; the fellow eye received a similar solution containing only 600 micrograms ascorbic acid. Following this treatment ERG recordings were performed at 1, 4, and 7 days. After the last recordings, animals were sacrificed and retinas were isolated for biochemical analyses. Significant and progressive reductions in retinal concentrations of dopamine (DA) and its main metabolites homovanillic acid (HVA), and dihydroxyphenylacetic acid (DOPAC) were found in treated retinas. Concentrations of norepinephrine (NE), serotonin (5HT), and 5 hydroxyindoleacetic acid (5-HIAA) were not affected, thus demonstrating the specific neurotoxic action of 6-OHDA on retinal dopaminergic neurons. Concurrently, significant increases in ERG a- and b-wave amplitudes as well as in implicit response times were observed. These electrophysiological changes were progressive reaching a maximum 7 days after intravitreal injections. Changes in b-wave amplitudes and response times were more pronounced at low intensities of stimulation. These results clearly show that, in rabbits, selective decreases in retinal DA concentrations result in pronounced ERG changes, which offer additional evidence supporting a role for this transmitter in lateral inhibition in the retina.

Animals

Pattern electroretinogram and optic nerve section in pigeons.

We studied the effect of optic nerve section on the pattern electroretinogram (PERG) of 10 pigeons. Base line PERG and flash ERG were measured prior to surgery and then one optic nerve was cut. We measured PERG at various time intervals up to 24 weeks after the section. There was a sharp drop in PERG amplitude immediately following the section. It gradually returned to normal levels in the following 24 weeks. Significant decreases in time to peak were noted at 1 and 16 weeks for 0.5 cycle per degree checks and at 1, 2 and 9 weeks for 0.25 cycle per degree checks. The ERG generated by a TV stimulus did not change in amplitude but had a shorter time to peak at 24 weeks for a high intensity stimulus and at 16, 18, 24 weeks for a low intensity stimulus. Light and electron microscopic sections (at 24 weeks) revealed an almost complete loss of nerve fibers in the optic nerve. Retinal sections revealed only a few surviving ganglion cells and a few nerve fibers. This suggests that in pigeons, PERG is not generated by ganglion cells.

Animals

Lobular delayed choroidal perfusion as an early angiographic sign of diabetic retinopathy: a preliminary report.

Between January 1982 and December 1983 stereo colour photography covering 10 standard fields of 30 degrees and fluorescein angiography were performed in 64 consecutive patients with diabetes mellitus who had no clinical evidence of diabetic retinopathy. Fifty-two patients were excluded on the basis of the slightest photographic or angiographic evidence of retinopathy or any other ocular disease. Electroretinogram oscillatory potentials were recorded in the remaining 12 patients. Four of the 12 had normal oscillatory potentials, colour photographs and angiograms, while 8 had angiographic evidence of lobular delayed choroidal perfusion and abnormal oscillatory potentials. Although only a small number of patients in the preclinical stages of diabetic retinopathy were studied, the results warrant that further attention be given to lobular delayed choroidal perfusion, which may represent early evidence of choroidal involvement in diabetic retinopathy.

Choroid

Rod-cone differences in response to retinal ischemia in rabbit.

Two series of experiments are reported on incremental increases of ischemia and monitoring of recovery from total ischemia of varying duration. In the first, rods show hyper-responses and cones do not; changes in amplitude and delays appear at higher levels of ischemia in cones than they do in rods. In the second series, cones do not recover up to control values with total ischemias of 30 min or more, while rods do recover and even show hyper-responses. Cones appear more resistant than rods to ischemia, but once affected do not recover as well as rods. Discussion proposes that these differences are specific to receptor systems of each rather than secondary to vascularization patterns.

Animals

Dose related effects of 6-OHDA on rabbit retinal dopamine concentrations and ERG B-wave amplitudes.

The purpose of this study was to examine the dose related effects of 6-hydroxydopamine (6-OHDA) on the electroretinographic (ERG) B-wave amplitude and on retinal concentrations of dopamine (DA) and its main metabolites homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC). Doses of 6-OHDA (60, 300 or 1200 micrograms) were dissolved in a 0.9 percent NaCl and ascorbic acid solution and administered intravitreally in 300 microliter volume in one eye of adult pigmented rabbits. The fellow eye received a similar volume of the drug vehicle. With the smallest dose of 6-OHDA (60 micrograms) no changes in ERG B-wave amplitude or retinal concentrations of DA, DOPAC or HVA were found. With the largest dose of 6-OHDA (1200 micrograms) complete extinction of the ERG and almost total disappearance of DA, DOPAC and HVA were observed. With the intermediate dose of 300 micrograms 6-OHDA significant increases in B-wave amplitudes and decreases in retinal DA, DOPAC and HVA concentrations were obtained. This latter dose did not affect retinal concentrations of serotonin (5-HT), 5-hydroxyindole acetic acid (5-HIAA) and norepinephrine (NE). These results demonstrate that selective reductions of retinal dopamine and its metabolites can be obtained with a single intravitreal injection of 300 micrograms 6-OHDA in rabbits. The observed concomitant increase in B-wave amplitudes lends support to the hypothesis that DA acts as a mediator of lateral inhibition in the retina.

3,4-Dihydroxyphenylacetic Acid

Pattern and flash electroretinogram following increased intraocular pressure in pigeons.

We have observed an increase in time to peak and a decrease in amplitude for both the pattern electroretinogram (PERG) and the electroretinogram (ERG) in pigeons following an elevation in intraocular pressure (IOP). The changes in PERG were highly correlated to the changes in ERG. However, they differed in that significant changes from baseline values occurred at lower levels of IOP for PERG than ERG for the amplitude, and in some cases for the time to peak.

Animals

Electroretinographic recovery from controlled total ischemia.

Three groups of animals were studied during the four-hour period following their recovery from total occlusion of retinal circulation for periods of 30, 60 and 90 minutes. During incremental increases of ischemia, recovery followed a pattern that is the reverse of that previously reported, inasmuch as wave amplitude is concerned. From total extinction, ERGs recovered and showed hyperresponses. Delays, however, behaved differently: they increased with recovery time--the opposite of what was expected. All signs were inversely proportional to the duration of ischemia. Sixty minutes of occlusion appears to be a threshold beyond which ERGs do not recover as well.

Animals

Electroretinographic signs of experimental chronic ischemia in the rabbit retina.

Chronic retinal ischemia was induced in rabbits by clamping the retrobulbar neurovascular pedicle of one eye. The other eye was used as a control. Electroretinograms (ERGs) were recorded for up to 32 weeks. The amplitude of the b-wave and of the oscillatory potentials showed a biphasic change: first a rapid drop below normal for 4 to 9 weeks, then an increase to above normal. The hyperresponsiveness was maintained up to the 32nd week. The implicit time of response was significantly modified only for the responses evoked by a low to moderate intensity of stimulation.

Animals

Electroretinographic evaluation of diabetic retinopathy: sensitivity of amplitude and time of response.

Amplitude and delay of oscillatory potentials were studied in the electroretinograms (ERGs) of patients with diabetes to see which was the more sensitive for evaluating diabetic retinopathy. Loss of amplitude was more sensitive in identifying eyes with early stages of retinopathy, in which funduscopic evidence of retinopathy was still absent, whereas delay of response was more sensitive in grading eyes with later stages. With cases classified according to stage of retinopathy, loss of amplitude and delay of response, a theoretic curve of the electrophysiologic time-course of diabetic retinopathy was drawn. The curve showed that amplitude can distinguish normal from preretinopathic eyes, that with a loss of amplitude of less than 50% no retinopathy will be found ophthalmoscopically, and that with a delay of response greater than 8% the delay will correlate well with the stage of retinopathy.

Diabetic Retinopathy

Effects of intensity of stimulation on signs of acute ischemia in the electroretinogram.

Acute retinal ischemia was induced in adult albino rabbits by clamping the retrobulbar blood vessels or raising the intraocular pressure. As the level of ischemia was increased, the b-wave amplitude and implicit time of response increased. However, the hyperresponsivity and delay of response were inversely related to the intensity of stimulation used, although at levels of ischemia above 70% there was a significant delay of response even with high-intensity stimulation. Thus, if early signs of acute ischemia are to be successfully monitored, low intensities of stimulation must be used.

Acute Disease

Effects of dark adaptation on implicit time in the clinical electroretinogram.

Electroretinograms were recorded from 11 normal human subjects during dark adaptation, either in full dark adaptation or in the presence of light backgrounds of various intensities. Although the amplitude varied considerably depending on the state of dark adaptation, the timing of the response appeared to be much less influenced. For practical purposes, in the absence of a significant background the timing of the response can be considered constant for a given intensity of stimulation, whatever the state of adaptation.

Adult

Hyper-response and delay in the electroretinogram in acute ischemia.

Acute ischemia was induced in 11 adult albino rabbits by clamping the retrobulbar blood vessels and in 5 others by raising the intraocular pressure. Total ischemia was achieved by raising the pressure in the hydraulic remote control system until total collapse of the retinal circulation was observed by indirect ophthalmoscopy and the response on the electroretinogram (ERG) disappeared. The level of ischemia was increased by 15% increments from 25% to 100%, and ERGs were recorded with a constant intensity of stimulation. The amplitude increased up to a peak at 55% ischemia, then decreased to extinction at 100% ischemia. The time of response increased to a maximum at 100% ischemia. The tentative conclusion is drawn that it is important to appreciate that ischemia, and not just degeneration, can cause a delay of the ERG response in humans.

Animals

Electroretinographic evidence of miosis-induced peripheral ring scotoma.

The results of a previous series of experiments in rabbits suggested that under scotopic conditions miosis elevates the electroretinogram (ERG) threshold by casting a peripheral ring scotoma. In the present work similar experiments failed to show any change in the ERG under photopic conditions.

Animals

Timing of the electroretinogram response and dark adaptation.

The time response of the Electroretinogram (ERG) is an essential part of the examination. Peak time of response increases with dark adaptation and decreases with the intensity of stimulation. When working with constant amplitude during dark adaptation sensitivity increases but the intensity of stimulation decreases. It is essential to clarify the relationship of these two factors for valid interpretation of results. The present work suggests that the state of adaptation or retinal sensitivity affects amplitude, while peak time of the response is modified by the absolute value of the stimulating source whatever the state of adaptation. This observation has been done on rod responses and is valid as long as pigments remain unbleached and able to respond.

Animals

ERG responses of rods and cones during dark adaptation.

We demonstrate the main electrophysiological events during dark adaptation. We correlate simultaneously the separate rod and cone responses, the ERC sensitivity curves, their timing and the biphasic dark adaptation curve.

Animals