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Biomedical subjects

S G Jacobson

Publications and source records attributed to S G Jacobson.

At least 19 recordsLinked to original sources
PubMed1992

Abnormal rod dark adaptation in autosomal dominant retinitis pigmentosa with proline-23-histidine rhodopsin mutation.

We studied rod and cone function in 13 patients from four families with autosomal dominant retinitis pigmentosa and the proline-23-histidine rhodopsin mutation. In patients with early stages of this disease, rod sensitivity was mildly abnormal throughout the retina and cone sensitivity was normal. In more severely affected patients, sensitivity loss varied with retinal region, some regions showing mild rod loss only and other regions having pronounced rod and cone dysfunction. Rhodopsin levels were decreased below normal by amounts that indicated the rod sensitivity loss was determined by the reduced ability to absorb light. The most characteristic abnormality of this genotype was a slowed rod branch of dark adaptation, which was present regardless of the extent or severity of disease. The time required for recovery of rod sensitivity was more than twice the normal time. These findings with dark-adapted perimetry, fundus reflectometry, and dark adaptometry showed intrafamilial and interfamilial consistency.

Adolescent↗
PubMed1992

Ultrastructure of connecting cilia in different forms of retinitis pigmentosa.

The connecting (sensory) cilium of rods and cones is the stalk that separates the outer segment, which contains visual pigment in stacks of membrane discs, from the inner segment, which contains cytoplasmic organelles involved in protein synthesis. There are conflicting reports on the occurrence of abnormal motile cilia in patients with retinitis pigmentosa (RP) and very few ultrastructural studies of photoreceptor connecting cilia in retinas from patients with RP. Defective connecting cilia could lead to the outer segment atrophy and degeneration that are characteristic of RP. The present study addresses the hypothesis that photoreceptor connecting cilia, as observed in cross section by electron microscopy, are defective in RP. We examined retinas from five patients with RP and four controls and found morphologic defects in the connecting cilia of one RP patient with type 2 Usher syndrome (86% abnormal, P less than .0001) but not in our sample of patients with X-linked (n = 2), simplex (n = 1), or autosomal dominant (n = 1) RP.

Adolescent↗
PubMed1992

Rhodopsin levels in the central retinas of normal miniature poodles and those with progressive rod-cone degeneration.

Visual pigment in normal miniature poodles and those with progressive rod-cone degeneration (prcd), a late-onset autosomal recessive photoreceptor degeneration, has been studied using imaging fundus reflectometry (IFR). The stage to which the disease had advanced in the animals with prcd was assessed with electroretinography (ERG). Measurements were carried out on seven affected, two heterozygous and three homozygous normal animals. The IFR measurements showed that the in situ difference spectrum of visual pigment measured in the central retina of the normal poodle is typical of vertebrate rhodopsin, with a maximum at about 510 nm. Rhodopsin regeneration following extensive bleaches continues for up to 70 min. In poodles with prcd, rhodopsin is spectrally normal and regenerates at normal rates. In young affected animals under 1 year of age, the final levels of rhodopsin could already be substantially reduced. Serial measurements of visual pigment in these dogs showed differences in the degree and spatial pattern of pigment loss and rate of progression between animals. The extent of visual pigment loss also differed among the older (greater than 4.5 years) affected animals: while in one animal no pigment could be detected, in another a central band of retina was relatively spared, and significant levels of visual pigment were measured within it. Pigment levels measured within the central 25 degrees of the retinas of poodles heterozygous for prcd were lower than those in normal animals, even though their ERGs were within the normal range.

Animals↗
PubMed1992

X-linked retinitis pigmentosa: functional phenotype of an RP2 genotype.

Rod- and cone-mediated function was studied with psychophysics and electroretinography in members of an X-linked retinitis pigmentosa pedigree with the RP2 genotype. An asymptomatic hemizygote with an early stage of the disease had cone dysfunction in the mid-periphery and an abnormal cone electroretinogram (ERG); rod function was normal. Hemizygotes with more advanced disease had cone and rod dysfunction in the mid-peripheral retina and cone dysfunction in the far periphery; cone and rod ERGs were abnormal. At very advanced stages, there was an absolute mid-peripheral scotoma and marked cone and rod dysfunction in the far peripheral and central retina. Cone and rod ERGs were severely abnormal or not detectable. Heterozygotes showed tapetal-like reflexes, patches of pigmentary retinopathy, and a range of functional findings from no detectable abnormalities to moderate levels of retinal dysfunction. There were regions of normal function adjacent to dysfunctional patches that had greater cone than rod sensitivity losses or comparable cone and rod losses. The results suggest that the phenotype of this RP2 genotype of X-linked retinitis pigmentosa, unlike other forms of retinitis pigmentosa, is first expressed as a cone photoreceptor system dysfunction, and as the disease progresses, both rod and cone systems are involved.

Adult↗
PubMed1991

Retinal function and rhodopsin levels in autosomal dominant retinitis pigmentosa with rhodopsin mutations.

We studied rod and cone function in 20 patients from six families with autosomal dominant retinitis pigmentosa, who represented five different point mutations in the gene encoding rhodopsin. In a family with a stop codon mutation at the carboxyl end of the molecule (glutamine-344), young members with the mutation were asymptomatic and clinically unaffected but showed about 1 log unit of rod sensitivity loss across the visual field and decreased rhodopsin levels; at this stage, cone function was essentially normal. In three families with mutations at the border of a transmembrane segment (arginine-135-leucine and arginine-135-tryptophan), there was neither detectable rod function nor measurable rhodopsin; cone function was variably impaired. Two families carrying different mutations (threonine-17-methionine and threonine-58-arginine) had altitudinal visual field defects with less impaired rod and cone function in the inferior than in the superior field. Rod adaptation was abnormal in both families, but the time course of adaptation differed between patients with the two mutations. Differences in the pattern of retinal dysfunction were therefore discernible in patients with different rhodopsin mutations.

Adolescent↗
PubMed1991

Rhodopsin mutations in autosomal dominant retinitis pigmentosa.

DNA samples from 161 unrelated patients with autosomal dominant retinitis pigmentosa were screened for point mutations in the rhodopsin gene by using the polymerase chain reaction and denaturing gradient gel electrophoresis. Thirty-nine patients were found to carry 1 of 13 different point mutations at 12 amino acid positions. The presence or absence of the mutations correlated with the presence or absence of retinitis pigmentosa in 174 out of 179 individuals tested in 17 families. The mutations were absent from 118 control subjects with normal vision.

Base Sequence↗
PubMed1991

Relatively enhanced S cone function in the Goldmann-Favre syndrome.

Using electrophysiologic and psychophysical tests that measure rod, midspectral, and S (blue) cone function, we studied four patients with the Goldmann-Favre syndrome, an autosomal recessive vitreoretinal degeneration. With spectral electroretinography, the predominant signal was from the S cones. With dark-adapted perimetry, all patients had severely reduced rod sensitivities and subnormal midspectral cone sensitivities. With S cone perimetry, the patients had normal or subnormal S cone function. Sensitivity differences between S and midspectral cones were significantly different from normal; there was relatively higher sensitivity to S cones compared to midspectral cones throughout the visual field. This relationship of dysfunctional cone mechanisms in the Goldmann-Favre syndrome is similar to that in the enhanced S cone syndrome, a recently identified retinal degeneration with S cone hypersensitivity. The results suggest that the Goldmann-Favre and the enhanced S cone syndromes are linked by a common pattern of retinal dysfunction.

Adult↗
PubMed1991

The distribution and kinetics of visual pigments in the owl monkey retina.

An imaging fundus reflectometer has been used to study the distribution and regeneration of visual pigments in the retina of the owl monkey, Aotes trivirgatus. Measurements were made over an area of retina from 10 degrees nasal to 30 degrees temporal on the horizontal meridian, and from 5 degrees inferior to 30 degrees superior on the vertical meridian. The measured density differences vary with retinal location, with values in the central retina higher than those in more peripheral regions. The area of high density differences is roughly circular, with the highest values (approximately 0.3 log units) centred on or near the area centralis. Spectral measurements are consistent with a rod visual pigment absorbing maximally at about 518 nm, and indicate that the contribution of cone pigments to the imaging fundus reflectometer (IFR) data is negligible everywhere within the retinal area studied. The distribution of density differences is shown to correlate well with anatomical data for receptor and ganglion cell populations. Bleaching the visual pigment with brief intense lights leads to the extensive formation of the long-lived photoproduct metarhodopsin 3. Complete regeneration of rhodopsin following a full bleaching exposure (whether of brief or extended duration) takes more than 60 min and the time course of its recovery cannot be described accurately by first order kinetics.

Animals↗
PubMed1990

Diagnostic clinical findings of a new syndrome with night blindness, maculopathy, and enhanced S cone sensitivity.

We studied eight patients who had night blindness, maculopathy (often cystoid), degenerative changes in the region of the vascular arcades, relatively mild visual field loss, and an unusual but characteristic electroretinogram. The dark-adapted electroretinogram showed no response to low-intensity stimuli that normally activate the rods, but large, slow responses to high-intensity stimuli. These large, slow waveforms persisted without change under light adaptation, and showed a striking mismatch to photopically balanced short and long wavelength stimuli (with sensitivity much greater to short than long wave-lengths). Since there is evidence from other studies that the electroretinogram and psychophysical responses represent hypersensitivity of short wavelength-sensitive (S or blue) cones, we propose that this disorder be called the enhanced S cone syndrome. There can be different degrees of severity in this syndrome, and progression appears to be slow.

Adolescent↗
PubMed1990

Patterns of rod and cone dysfunction in Bardet-Biedl syndrome.

We studied visual function in 16 patients with the Bardet-Biedl syndrome. Visual acuity, kinetic perimetry, and electroretinography results indicated a severe loss of central and peripheral vision and rod and cone function by the second or third decade of life. Light- and dark-adapted static perimetry in patients 10 to 15 years of age with early involvement showed a parallel and marked loss of rod and cone sensitivity across the visual field. Patients with more advanced disease and no measurable peripheral visual field showed different patterns of central visual dysfunction: an island of only cone function centered in a bull's-eye lesion; patches of rod function surrounding geographic atrophy; or a central island of excellent rod sensitivity but severely impaired cones. In the two least-affected patients, a 13-year-old boy and the asymptomatic 45-year-old sibling of a patient, there were more rod than cone abnormalities as determined by electroretinography and static perimetry.

Adolescent↗
PubMed1990

Photoreceptor rosettes with blue cone opsin immunoreactivity in retinitis pigmentosa.

Immunocytochemistry has rarely been performed on donor retinas from patients with retinitis pigmentosa (RP), due to routine storage of tissues in fixatives that reduce or destroy antigenicity. The authors have developed a method to circumvent this problem and report light and electron microscopic histopathology and immunocytochemistry of an unusual retina from a 76-year-old man with multiplex RP. The retina shows loss of photoreceptors throughout (particularly rods), shortened foveal cone outer segments, and displaced photoreceptors in rosettes and tubules, an atypical pattern for RP. Antigenicity was recovered in this retina by treatment with sodium borohydride, and 17 antigens normally found in retina are present with expected distribution, although many cells have abnormal morphology. Most cone outer segments are immunoreactive with anti-blue but not anti-red/green cone opsin, whereas blue cone sensitivity is preferentially lost in many cases of RP. Psychophysical testing of the patient's sister, who has the same retinal disease, showed reduced rod and red/green cone sensitivities. This was consistent with the diminished numbers and size of rods and red/green cones found by immunocytochemistry in her brother's retina. The sister did not show blue cone hypersensitivity characteristic of a recently described retinal degeneration known as the "enhanced S cone syndrome."

Aged↗
PubMed1990

[Modification of an automated perimeter for dark- and light-adapted perimetry].

A modified automated projection static perimeter which can measure thresholds with lights of three different wavelengths in light-adapted as well as in dark adapted state is described. With the modifications described, this instrument can evaluate relative states of rod and cone mechanisms respectively within the visual field range of 72 degrees. These modifications also enable dark-adapted two-color static perimetry quantitatively across the visual field including profile measurement. Results obtained from normal subjects with these techniques permit assessment of the sensitivity in dark and light and also determination of photoreceptor mediation in the dark. These techniques can evaluate rod and cone dysfunctions separately unlike other retinal function tests, and may show that different mechanisms even in one clinical entity of retinal dystrophies, as well as retinal degenerations, can be demonstrated.

Adaptation, Ocular↗
PubMed1990

SWS (blue) cone hypersensitivity in a newly identified retinal degeneration.

Photoreceptor-mediated mechanisms were studied in patients with a recently identified retinopathy typified by night blindness, cystoid maculopathy, and similar scotopic and photopic electroretinograms (ERGs). Dark-adapted spectral sensitivity functions were only partly explained as composites of rod and cone curves shifted to lower sensitivities; there was unusually high sensitivity from 400-460 nm. A rod mechanism, reduced in sensitivity by at least 3 log units, was detectable with dark adaptometry. No measurable rhodopsin was found with fundus reflectometry. Light-adapted spectral sensitivities were subnormal for wavelengths greater than 500 nm but supernormal from 420-460 nm. On a yellow adapting field, the supernormal spectrum approximated that of the short-wavelength-sensitive (SWS) cone system. With spectral ERGs, two mechanisms were demonstrated. Dark- and light-adapted ERGs to green, orange-yellow, and red stimuli had similar waveforms and coincident intensity-response functions on a photopic intensity axis. ERGs to blue and blue-green stimuli were similar, and intensity-response functions coincided on a SWS cone intensity axis. Patients varied in the degree to which rod and midspectral cone function were decreased and SWS cone function was increased.

Adolescent↗
PubMed1989

Cone-rod dystrophy. Phenotypic diversity by retinal function testing.

Three patterns of visual dysfunction were identified in patients with autosomal recessive or simplex cone-rod dystrophy using rod and cone electroretinography and light- and dark-adapted static threshold perimetry. In the first pattern, there was a central rod and cone scotoma with eccentric fixation, mild peripheral retinal dysfunction equally affecting rod and cone systems, and slow progression. The second pattern, which was relatively more severe, also showed a central rod and cone scotoma and eccentric fixation; however, there was more cone than rod dysfunction detected by electroretinography, and function was lost in the peripheral visual field before it was lost in the midperipheral field. A third pattern, which was rapidly progressive, showed central unsteady fixation and no measurable cone function. Patches of rod function were retained in the central and inferotemporal regions of the visual field. Most of the patients studied fit within the three patterns and the patterns were consistent within families.

Adolescent↗
PubMed1989

Evaluation of eyes with stage-5 retinopathy of prematurity.

Recent advances in vitreous microsurgical techniques described by Machemer, Charles, Hirose, Trese, de Juan, and others have resulted in successful anatomical reattachment of eyes with stage-5 retinopathy of prematurity (ROP). Such eyes had previously been classified as inoperable. Although nearly 50% of eyes achieve an anatomical reattachment of the posterior retina, from 10% to 30% of the reattached eyes reported to date have no light perception. Infants with stage-5 ROP in both eyes may be quite difficult to evaluate preoperatively, particularly with regard to visual function and the configuration of the retinal detachment. Protocols for obtaining a bright flash visually evoked potential (VEP) and standardized echography have been developed to determine the following: 1. Objective evidence of visual function in one or both eyes 2. The configuration and characteristics of the retinal detachment It is hoped that such prospective evaluation will help to identify those eyes with the best prognosis for both visual anatomical success.

Evoked Potentials, Visual↗
PubMed1989

Interocular asymmetry of visual function in heterozygotes of X-linked retinitis pigmentosa.

Heterozygotes of X-linked retinitis pigmentosa were studied with full field rod and cone electroretinography and light adapted kinetic perimetry. Twelve parameters from the electroretinograms (ERGs) and two parameters from the kinetic visual fields of both eyes of 22 heterozygotes were measured and statistical comparisons made with results from female control subjects. Rod and cone ERG amplitude parameters were significantly lower and cone timing delayed in the heterozygotes. Most of the ERG parameters that were abnormal in measured value also showed significantly greater interocular differences compared with controls. Kinetic visual fields with both V-4e and I-4e test targets were smaller in heterozygotes than in controls. Only with the I-4e target, however, were interocular differences significantly larger in the heterozygotes. For the I-4e target and many of the ERG parameters, using the interocular difference in conjunction with the measured parameter value from a single eye significantly increased the efficacy of discrimination between heterozygotes and controls; for some ERG parameters, the interocular difference alone provided the best separation of the two groups.

Adolescent↗
PubMed1989

Rhodopsin levels and retinal function in cats during recovery from vitamin A deficiency.

Extended vitamin A deficiency in the cat led to an abnormal appearance in the tapetal fundus with the formation of a dark brown streak centered on the area centralis. At this time rod sensitivity, as measured by the b-wave of the electroretinogram, was reduced by more than two log units; the level of rod visual pigment was reduced by about 90% throughout the paracentral retinal region and was essentially absent from the area centralis. Following oral supplementation with vitamin A there was a rapid partial recovery of both rhodopsin levels and rod sensitivity. Further recovery continued over more than 18 days to levels that were not substantially below normal. This recovery was absent from the area centralis, in which measured visual pigment levels remained very low. In supplemented cats, the brown color in the fundus faded but there remained a small hyper-reflective zone at the area centralis. Morphological examination of the central retina in a supplemented cat showed an outer nuclear layer reduced to one or two rows in the small zone with low rhodopsin levels. Cone but not rod photoreceptors were present in this zone and they appeared to lack outer segments. During recovery, the increase in rod sensitivity was approximately linearly related to the recovery of rhodopsin levels. Thus, in these conditions reduction in sensitivity resulting from previous vitamin A deficiency was limited by the ability of the photoreceptors to absorb incident quanta. The time course of the recovery of rhodopsin and sensitivity suggests that at least two processes were involved. The faster of these may be the regeneration of rhodopsin from existing opsin molecules in the outer segments, while the slower may depend on the renewal of the outer segments themselves.

Animals↗