Biomedical subjects

M A Sandberg

Publications and source records attributed to M A Sandberg.

At least 55 records · Page 3Linked to original sources

PubMed1991

Relationship of oscillatory potential amplitude to A-wave slope over a range of flash luminances in normal subjects.

The effect of flash luminance on the relationship of oscillatory potential (OP) amplitude, as a measurement of inner retinal function, to a-wave slope, as a measurement of photoreceptor function, was evaluated in full-field electroretinograms recorded from normal subjects. The ratio of OP amplitude to a-wave slope was found to be independent of flash luminance over a 3000-fold luminance range. This finding raises the possibility that a reduction in the ratio of OP amplitude to a-wave slope in eyes with media opacities may be used as a sign of inner retinal malfunction. Selected cases are presented to illustrate application of this approach.

Adult↗

PubMed1990

Mutations within the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa.

BACKGROUND: Night blindness is an early symptom of retinitis pigmentosa. The rod photoreceptors are responsible for night vision and use rhodopsin as the photosensitive pigment. METHODS AND RESULTS: We found three mutations in the human rhodopsin gene; each occurred exclusively in the affected members of some families with autosomal dominant retinitis pigmentosa. Two mutations were C-to-T transitions involving separate nucleotides of codon 347; the third was a C-to-G transversion in codon 58. Each mutation corresponded to a change in one amino acid residue in the rhodopsin molecule. None of these mutations were found in 106 unrelated normal subjects who served as controls. When the incidence of these three mutations was added to that of a previously reported mutation involving codon 23, 27 of 150 unrelated patients with autosomal dominant retinitis pigmentosa (18 percent) were found to carry one of these four defects in the rhodopsin gene. All 27 patients had abnormal rod function on monitoring of their electroretinograms. It appears that patients with the mutation involving codon 23 probably descend from a single ancestor. CONCLUSIONS: In some patients with autosomal dominant retinitis pigmentosa, the disease is caused by one of a variety of mutations of the rhodopsin gene.

Base Sequence↗

PubMed1990

A point mutation of the rhodopsin gene in one form of retinitis pigmentosa.

The gene for autosomal dominant retinitis pigmentosa in a large pedigree of Irish origin has recently been found to be linked to an anonymous polymorphic sequence, D3S47 (C17), from the long arm of chromosome 3. As the gene coding for rhodopsin is also assigned to the long arm of chromosome 3 and is expressed in rod photoreceptors that are affected early in this blinding disease, we searched for a mutation of the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa. We found a C----A transversion in codon 23 (corresponding to a proline----histidine substitution) in 17 of 148 unrelated patients and not in any of 102 unaffected individuals. This result, coupled with the fact that the proline normally present at position 23 is highly conserved among the opsins and related G-protein receptors, indicates that this mutation could be the cause of one form of autosomal dominant retinitis pigmentosa.

Adult↗

PubMed1990

Rod electroretinograms in an elevated cyclic guanosine monophosphate-type human retinal degeneration. Comparison with retinitis pigmentosa.

Unusual rod electroretinogram (ERG) intensity-response functions were recorded from three female patients with retinal degeneration who had visual acuities of 20/200, retinal arteriolar narrowing, and diffuse granularity of the retinal pigment epithelium. All three patients had rod b-waves that were profoundly subnormal in amplitude and markedly delayed in implicit time to bright stimuli. Rod a-wave slopes were reduced 50% below normal, indicating photoreceptor involvement. These unusual rod ERG intensity-response functions are similar to those previously reported for the isolated cat eye with elevated retinal cyclic guanosine monophosphate (cGMP) after perfusion with isobutylmethylxanthine. This finding supports the idea that these three patients may have an elevation of retinal cGMP. Their rod ERG intensity-response functions are contrasted with those recorded from some patients with retinitis pigmentosa.

1-Methyl-3-isobutylxanthine↗

PubMed1989

An electroretinographic and molecular genetic study of X-linked cone degeneration.

We evaluated full-field electroretinograms from members of a family with X-linked cone degeneration. The 15-year-old propositus had near normal visual acuity and a protan deficiency. His maternal grandfather and great uncle had a visual acuity of 20/200, a deficiency in color vision, and signs of macular degeneration; all had normal rod electroretinographic responses and diminished cone electroretinographic responses. The mother and maternal aunt of the propositus had normal visual acuity and diminished cone electroretinograms with predominant loss of red cone function. Their cone responses were greater than those of affected males. Genomic DNA isolated from these patients was analyzed with a red cone pigment gene cDNA probe that disclosed a 6.5-kilobase deletion in the red cone pigment gene. These findings substantiate that a defect in a gene encoding for a cone photoreceptor protein can lead to a cone photoreceptor degeneration.

Adolescent↗

PubMed1989

Effects of 2-amino-4-phosphonobutyric acid (APB) and glycine on the oscillatory potentials of the rat electroretinogram.

Oscillatory potentials of the electroretinogram were monitored in dark-adapted rats following intravitreal injection of 2-amino-4-phosphonobutyric acid (APB), a glutamate analog that preferentially blocks the light response of depolarizing bipolar cells, or glycine, a known endogenous inhibitory neurotransmitter that suppresses the light response of cells in the inner retina postsynaptic to glycinergic neurons. Oscillatory potentials were abolished in conjunction with the b-wave with APB and selectively reduced or eliminated by glycine: neither agent attenuated the a-wave. The results are compatible with the idea that light-induced depolarizing bipolar cell, hyperpolarizing bipolar cell, and glycinergic amacrine cell responses are all necessary for the generation of oscillatory potentials in the rat. The results also suggest that hyperpolarizing bipolar cells do not contribute to b-wave generation.

Aminobutyrates↗

PubMed1988

Narrow-band filtering for monitoring low-amplitude cone electroretinograms in retinitis pigmentosa.

Low amplitude (less than 10 microV) cone electroretinograms, elicited with 30-Hz white flicker from 59 patients with retinitis pigmentosa, were computer-averaged alone or in combination with a narrow-band electronic filter that increases the signal to noise ratio, thereby making it possible to evaluate the electroretinograms of most patients with retinitis pigmentosa. Narrow-band filtering reduced the amplitude of computer-averaged responses by an average of 7%, but the change in amplitude was independent of the size of the unbandpassed response. Narrow-band filtering also allowed measurement of 30-Hz cone responses in patients followed up over an 11- to 15-year period and quantitation of responses of less than 1 microV, which were not detectable with computer averaging alone.

Adolescent↗

PubMed1988

Diurnal rhythm in the electroretinogram of the Royal College of Surgeons (RCS) pigmented rat.

RCS pigmented rats, born and raised in cyclic light for 22-23 days and then placed in darkness for up to 24 hr, showed a diurnal rhythm in the rod electroretinogram (ERG) that was comparable with that seen in normal pigmented rats. a-Wave and b-wave sensitivities were 21- and 34% lower, respectively, 1.5 hr after expected light onset compared with those at other times of day. In contrast to findings in normal rats, however, these sensitivity decreases in the RCS rats were not associated with an increase in the frequency of large phagosomes in the pigment epithelium; phagosome frequency was subnormal and relatively constant over the day. These findings suggest that depressed ERG sensitivities 1.5 hr after expected light onset in both normal and RCS pigmented rats reflect altered rod photoreceptor function associated with the process of outer-segment disc shedding and not with engulfment of shed discs into phagosomes by the pigment epithelium.

Animals↗

PubMed1988

Rod ERG diurnal rhythm in some patients with dominant retinitis pigmentosa.

Five patients with dominant retinitis pigmentosa who were monocularly entrained to a 14 hr light: 10 hr dark cycle showed an abnormal diurnal rhythm in the rod electroretinogram of the entrained eye. These patients as a group showed larger-than-normal reductions in b-wave sensitivity 1.5 hr and 8 hr after light onset relative to other times of day. The findings raise the possibility that these patients have an abnormality in rod photoreceptor function associated with the process of outer segment renewal.

Adult↗

PubMed1987

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.

Adolescent↗

PubMed1987

Effects of IBMX on the ERG of the isolated perfused cat eye.

Full-field electroretinograms (ERGs) were recorded from isolated cat eyes perfused through the ophthalmociliary artery with isobutylmethylxanthine (IBMX), an inhibitor of cyclic guanosine monophosphate (cyclic GMP) phosphodiesterase. Low doses of IBMX (0.1-0.3 mM) produced decreased rod ERG amplitudes at low stimulus luminances and increased rod ERG amplitudes at high stimulus luminances. A high dose of IBMX (1.0 mM) initially produced the same effect as the low doses and then led to decreased rod ERG amplitudes at all stimulus luminances. Perfusion with IBMX also resulted in elevations in the semi-saturation luminance (sigma), delayed rod a-wave latencies, delayed rod a-wave and b-wave implicit times, and reduced rod a-wave slopes. Eyes perfused with IBMX (1.0 mM) were also found to have elevated levels of retinal cyclic GMP. These effects of IBMX on the rod ERG are considered in the context of previously described ERGs in selected cases of human retinal degeneration.

1-Methyl-3-isobutylxanthine↗

PubMed1986

Electroretinograms in carriers of blue cone monochromatism.

We recorded full-field electroretinograms from seven female obligate carriers of X-linked blue cone monochromatism and eight daughters of obligate carriers. We observed that all obligate carriers had one or more of the following abnormalities: delayed cone b-wave implicit times to 30-Hz white flicker, loss of the a1 oscillation in responses to single flashes of white light under dark-adapted conditions, subnormal b-wave amplitudes to single flashes of white light under dark-adapted conditions, and subnormal cone responses to 30-Hz white flicker. All had normal rod responses to blue light. Three of eight daughters of obligate carriers had abnormal electroretinograms comparable to those recorded from obligate carriers. These obligate carriers have a partial but comparable deficiency of red and green cone function.

Adult↗

PubMed1986

Electroretinogram (ERG) sensitivity and phagosome frequency in the normal pigmented rat.

Normal adult pigmented rats, born and raised in cyclic light for 25- to 27 days and then placed in darkness for up to 24 hr, showed an inverse relation between electroretinogram (ERG) sensitivity and phagosome frequency in the pigment epithelium over the course of a day. Linear regression revealed that a two-fold increase in the frequency of large phagosomes was associated with approximately a one-third decrease in ERG sensitivity. The observed 37-40% decline in ERG sensitivity 1.5 hr after expected light onset was significantly greater than what would be expected from the measured 11% shortening of rod outer segments at that time of day. Possible explanations for this disparity are considered.

Animals↗

PubMed1986

Full-field electroretinograms in miniature poodles with progressive rod-cone degeneration.

Full-field electroretinograms (ERGs) were recorded between the ages of 4 and 34 months from 8 miniature French poodles with inherited progressive rod-cone degeneration (PRCD) and from 11 normal miniature poodles. Three stages of retinal function were observed in the affected dogs, although the ages of transition from one stage to the next were variable among dogs. Rod and cone ERGs were normal in amplitude in the first stage, rod ERGs were reduced in amplitude and cone ERGs were normal in the second, and rod ERGs were extremely reduced in amplitude or nondetectable and cone ERGs were reduced in amplitude in the third. On average, these poodles with PRCD lost 7.2% of remaining rod amplitude per month and 2% of remaining cone amplitude per month. Affected poodles had normal rod and cone b-wave implicit times over all three stages, in contrast to humans with the early stages of progressive forms of retinitis pigmentosa who have delayed rod and/or cone b-wave implicit times.

Animals↗

PubMed1986

Diurnal rhythm in the human rod ERG. Relationship to cyclic lighting.

Five normal subjects were monitored with periodic full-field ERG testing during entrainment to a 14L:10D lighting cycle. On the second day of entrainment, mean ERG threshold was significantly higher 1.5 hr after light onset than at other times of day and was comparable to a previously reported threshold elevation following 7 days of entrainment. This diurnal rhythm was not detectable in eyes entrained for 3 days that were then maintained in darkness for 1 day. The findings support the idea that 2 days of entrainment are required to maximize the diurnal rhythm in the human rod ERG and that an adapting light may be required to trigger this rhythm.

Adaptation, Ocular↗

PubMed1985

Natural course of retinitis pigmentosa over a three-year interval.

Ninety-four patients, 6 to 49 years old, with progressive forms of retinitis pigmentosa were examined at baseline and annually for three consecutive years with respect to visual acuity, kinetic visual fields, dark-adaptation thresholds, computer-averaged electroretinograms, and fundus photographs. A subset was recalled within two months of a given visit to measure intervisit variability and to develop criteria for what constitutes significant (P less than .01) functional change. Over a three-year interval full-field electroretinograms declined significantly in 66 of 86 patients (77%) with detectable responses at baseline. Patients lost an average of 16% to 18.5% of remaining electroretinographic amplitude per year and 4.6% of remaining visual field area per year. Bone spicule pigmentation increased in 41 of 76 patients for whom we could make comparisons over a three-year interval (54%). Visual acuity and dark-adaptation thresholds remained relatively stable.

Adolescent↗

PubMed1985

Enhancement of (polyA+)RNA synthesis in light in isolated intact photoreceptor cells of the rat.

Incorporation of [3H]-cytidine into messenger RNAs (polyadenylated RNAs) was enhanced in light in isolated intact photoreceptor cells of the rat. The increase in polyadenylated (PolyA+)RNAs appeared selective relative to other photoreceptor RNAs since incorporation of [3H]-cytidine into this fraction was up to 10-fold higher while labeling of total cellular RNAs was only two- to three-fold higher in light compared with dark. The photoreceptor cells were isolated in vivo through destruction of inner retina neurons with injections of combinations of neurotoxic substances during early postnatal development. The photoreceptor cells attained normal adult morphology and function: the alpha-wave of the electroretinogram, as well as the thickness of the outer nuclear layer and the length of photoreceptor inner and outer segments, were found to be within the normal range at 4 and 10 weeks of age. In addition to RNA synthesis, such photoreceptor cell preparations when incubated in vitro demonstrated a capacity for regulating light-dependent sodium fluxes comparable to that within the intact retina. The potential usefulness of this model for exploring the molecular biology of photoreceptor cells is discussed.

Animals↗

PubMed1984

Diurnal rhythm in the human rod ERG.

Six normal subjects, monocularly entrained to a 14 hr light/10 hr dark cycle, showed a diurnal rhythm in the rod ERG of the entrained eye but not the unentrained eye. Thresholds in the entrained eye were significantly higher 1 1/2 hrs after light onset than at other times. This threshold increase occurred at a time when rod disc shedding has been observed histologically to be maximal in light-entrained animals.

Adaptation, Ocular↗