Search PubMed⌕ Search

Biomedical subjects

E L Berson

Publications and source records attributed to E L Berson.

At least 19 recordsLinked to original sources
PubMed1996

Evaluation of patients with retinitis pigmentosa receiving electric stimulation, ozonated blood, and ocular surgery in Cuba.

OBJECTIVE: To evaluate the effect of intervention with electric stimulation, autotransfused ozonated blood, and ocular surgery, performed in Cuba, on the course of the common forms of retinitis pigmentosa. DESIGN: Ocular evaluations over 6 to 8 months before and after intervention in Cuba. SETTING: Evaluations performed at a US clinical research facility. PATIENTS: Ten adult patients aged 25 to 67 years with retinitis pigmentosa. MAIN OUTCOME MEASURES: Visual acuity, visual field area, and electroretinogram (ERG) amplitude. RESULTS: No significant change in visual acuity or visual field area was observed on average between preintervention and postintervention values over a 6- to 8-month interval. Mean 30-Hz cone ERG amplitude declined by 15.5% between preintervention and postintervention values (P = .006). When data on change in visual field area from 1 statistically significant outlier were excluded from the analysis, a significant decline of 12.9% in mean visual field area was observed (P = .025). CONCLUSIONS: These data support the conclusion that the intervention offered in Cuba provides no benefit to patients with retinitis pigmentosa as measured by visual acuity, visual field area, and ERG. The magnitudes of the mean declines observed in ERG amplitude and visual field area over a 6- to 8-month interval, relative to those reported in previous studies, raise the possibility that this intervention may worsen the course of the disease.

Adult↗
PubMed1996

Clinical and histopathologic findings in clumped pigmentary retinal degeneration.

OBJECTIVE: To describe the clinical and histopathologic features of clumped pigmentary retinal degeneration (CPRD). DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Twenty-four patients, aged 7 to 83 years, were identified from the medical record filed of the Berman-Gund Laboratory, Boston, Mass, as having the clinical features of CPRD. The autopsy eye from a 56-year-old man with CPRD was studied with light and electron microscopy. MAIN OUTCOME MEASURES: Visual acuities, visual fields, dark-adaptation thresholds, and results of electroretinograms; histopathologic study of an autopsy eye. RESULTS: The functional deficit of patients with CPRD seems to be similar to that of patients with typical retinitis pigmentosa. Different degrees of severity were observed among patients of similar age. The histopathologic data showed that the clinically distinct areas of clumped pigment are due to excessive accumulation of melanin granules in retinal pigment epithelial cells. CONCLUSION: Based on the distinct clinical and histopathologic appearance, CPRD should be considered as a separate form of retinal degeneration.

Adolescent↗
PubMed1996

Isolation of focal rod electroretinograms from the dark-adapted human eye.

PURPOSE: To isolate focal rod electroretinograms (ERGs) from the dark-adapted human eye. METHODS: In two normal volunteers, dark-adapted focal rod ERGs were recorded from the peripheral retina in response to 30 degree diameter blue flashes of varying retinal illuminance and from different retinal regions in response to 10 degree diameter bright blue flashes. Dark-adapted focal rod ERGs also were recorded from a patient with the multiple evanescent white dot syndrome (MEWDS) and an enlarged blind spot in response to 30 degree diameter blue flashes presented within and outside the scotoma. The slower and larger stray light rod component elicited by these flashes was removed by subtracting the matching rod response to a dimmer, full-field flash, or was ignored when it did not overlap the faster and smaller focal rod component. RESULTS: The focal rod ERG had a waveform and sensitivity similar to those of the full-field rod ERG, was approximately proportional in amplitude to the density of rods directly illuminated, and was nondetectable within the retinal area corresponding to the enlarged blind spot of the patient with MEWDS. CONCLUSIONS: Focal rod ERG a- and b-waves, in response to stimuli as small as 10 degrees, can be recorded from different regions of the dark-adapted human retina to evaluate localized rod function.

Adult↗
PubMed1996

The relationship between visual field size and electroretinogram amplitude in retinitis pigmentosa.

PURPOSE: To determine to what degree visual field size is correlated with electroretinogram (ERG) amplitude among patients with the common forms of retinitis pigmentosa (RP). METHODS: Visual field equivalent diameter to the V4e white test light of the Goldmann perimeter was correlated with log ERG amplitude elicited by 0.5 Hz or 30 Hz full-field flashes of white light. Primary analyses were conducted on data from 583 patients with the common forms of RP. Subset analyses were performed on data from patients with ERG responses with different ranges of amplitude to assess to what extent the correlation depends on ERG amplitude, as well as on data from patients of a given genetic type to determine whether the correlation depends on the mode of transmission. Data from patients with the rhodopsin, Pro23His mutation (n = 38) or with the rhodopsin, Pro347Leu mutation (n = 24) were analyzed to determine the correlation between visual field size and ERG amplitude for patients with the same mutation. RESULTS: Visual field size was significantly correlated with ERG amplitude for every comparison (P < or = 0.0003). Correlations generally were higher for ERGs elicited by 30 Hz flashes (r = 0.62 for the entire sample) than they were for those elicited by 0.5 Hz flashes (r = 0.53 for the entire sample). They were lower for truncated ranges of ERG amplitude, higher for patients with dominant or recessive disease than for patients with x-linked disease or for patients of all genetic types combined, and strong for patients with the same rhodopsin mutation (reaching a value of 0.87). CONCLUSIONS: Visual field size is significantly correlated with ERG amplitude for patients with RP. Correlation depends on the range of ERG amplitudes, the inheritance type, and, particularly, on whether the analysis is confined to a single gene mutation.

Adolescent↗
PubMed1995

Mutations in the gene encoding the alpha subunit of the rod cGMP-gated channel in autosomal recessive retinitis pigmentosa.

Mutations in the genes encoding two proteins of the retinal rod phototransduction cascade, opsin and the beta subunit of rod cGMP phosphodiesterase, cause retinitis pigmentosa (RP) in some families. Here we report defects in a third member of this biochemical pathway in still other patients with this disease. We screened 94 unrelated patients with autosomal dominant RP and 173 unrelated patients with autosomal recessive RP for mutations in the gene encoding the alpha subunit of the rod cGMP-gated cation channel. Five mutant sequences cosegregated with disease among four unrelated families with autosomal recessive RP. Two of these were nonsense mutations early in the reading frame (Glu76End and Lys139End) and one was a deletion encompassing most if not all of the transcriptional unit; these three alleles would not be expected to encode a functional channel. The remaining two mutations were a missense mutation (Ser316Phe) and a frameshift [Arg654(1-bp del)] mutation truncating the last 32 aa in the C terminus. The latter two mutations were expressed in vitro and found to encode proteins that were predominantly retained inside the cell instead of being targeted to the plasma membrane. We conclude that the absence or paucity of functional cGMP-gated cation channels in the plasma membrane is deleterious to rod photoreceptors and is an uncommon cause of RP.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1995

Mutation spectrum of the gene encoding the beta subunit of rod phosphodiesterase among patients with autosomal recessive retinitis pigmentosa.

Mutations in the gene encoding the beta subunit of rod cGMP phosphodiesterase are known causes of photoreceptor degeneration in two animal models of retinitis pigmentosa, the rd (retinal degeneration) mouse and the Irish setter dog with rod/cone dysplasia. Here we report a screen of 92 unrelated patients with autosomal recessive retinitis pigmentosa for defects in the human homologue of this gene. We identified seven different mutations that cosegregate with the disease. They were found among four patients with each patient heterozygously carrying two mutations. All of these mutations are predicted to affect the putative catalytic domain, probably leading to a decrease in phosphodiesterase activity and an increase in cGMP levels within rod photoreceptors. Mutations in the gene encoding the beta subunit of rod phosphodiesterase are the most common identified cause of autosomal recessive retinitis pigmentosa, accounting for approximately 4% of cases in North America.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1995

Constitutive activation of phototransduction by K296E opsin is not a cause of photoreceptor degeneration.

The missense mutation Lys-296-->Glu (K296E) in the rhodopsin gene produces an opsin with no chromophore binding site and therefore is not activated by light. Nevertheless, the mutant opsin constitutively activates transducin in vitro and causes photoreceptor degeneration in vivo, possibly by continuously activating the phototransduction cascade, analogous to constant exposure to environmental light. We studied the K296E mutation in eight lines of transgenic mice. Each line developed photoreceptor degeneration with the rate of degeneration increasing monotonically as the ratio of mutant:wild-type opsin mRNA increased. At no time in the course of degeneration was there endogenous light adaptation in the retina as measured by the electroretinogram. The mutant opsin was found to be invariably phosphorylated and stably bound to arrestin. Light-independent activation of transducin was demonstrated only after the removal of arrestin and dephosphorylation of K296E opsin. Thus, K296E opsin in vivo does not activate the phototransduction cascade because it is shut off by photoreceptor inactivation mechanisms. Our data show that the K296E mutation does not cause photoreceptor degeneration by continuous activation of phototransduction.

Animals↗
PubMed1995

Mapping of the human cone transducin alpha-subunit (GNAT2) gene to 1p13 and negative mutation analysis in patients with Stargardt disease.

We report localization of the human cone transducin (GNAT2) gene using fluorescence in situ hybridization on chromosome 1 in band p13. The recent assignment of a gene for Stargardt disease to the same chromosomal region by linkage analysis prompted us to investigate the possible role of GNAT2 in the pathogenesis of this disease. We investigated 66 unrelated patients for mutations in the coding region of the GNAT2 gene using polymerase chain reaction-single strand conformation polymorphism analysis (SSCP) and direct sequencing. No disease-specific mutations were found, indicating that GNAT2 is probably not involved in the pathogenesis of most cases of Stargardt disease.

Base Sequence↗
PubMed1995

Autosomal recessive retinitis pigmentosa caused by mutations in the alpha subunit of rod cGMP phosphodiesterase.

Retinitis pigmentosa (RP) constitutes a group of genetically heterogeneous progressive photoreceptor degenerations leading to blindness and affecting 50,000-100,000 people in the U.S. alone. Over 20 different RP loci have been mapped, of which six have been identified. Three of these encode members of the rod photoreceptor visual transduction cascade: rhodopsin, the rod cGMP-gated cation channel alpha subunit, and the beta subunit of cGMP-phosphodiesterase (PDEB). As null mutations in PDEB cause some cases of RP and since both alpha and beta subunits are required for full phosphodiesterase activity, we examined the gene encoding the alpha subunit of cGMP phosphodiesterase (PDEA) in 340 unrelated patients with RP. We found three point mutations in PDEA in affected members of two pedigrees with recessive RP. Each mutation alters an essential functional domain of the encoded protein and likely disrupts its catalytic function. PDEA is the seventh RP gene identified, highlighting the extensive genetic heterogeneity of the disorder and encouraging further investigation into the role of other members of the phototransduction cascade in RP.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1995

Low incidence of retinitis pigmentosa among heterozygous carriers of a specific rhodopsin splice site mutation.

PURPOSE: To determine whether a rhodopsin splice donor site mutation at the 5' end of intron 4 is a cause of autosomal dominant retinitis pigmentosa. METHODS: Heterozygous carriers of the same rhodopsin splice site mutation in two pedigrees were identified using single-strand conformation polymorphism analysis. Twelve heterozygous carriers were evaluated by ophthalmoscopy. Goldmann kinetic visual fields, dark adaptation thresholds, and full-field electroretinograms including rod intensity-response functions. Clinical findings from the heterozygous carriers of the splice site mutation were compared with those from heterozygous carriers from a separate family with a known recessive rhodopsin null mutation, Glu249X. RESULTS: Analysis of DNA from 48 members of two pedigrees revealed 25 heterozygous carriers of the splice site mutation, ranging in age from 14 to 82 years. There were no homozygotes with the rhodopsin splice site mutation. Of the 25 heterozygous carriers, 24 were asymptomatic. Eleven asymptomatic heterozygotes were examined, including four older than 65 years of age. They were found to have normal fundi, full visual fields, and slightly elevated final rod dark adaptation thresholds. Their rod electroretinographic b-wave amplitudes were slightly diminished over the full range of blue light intensities. Rod a-wave implicit times were slightly but significantly prolonged in response to the brightest blue flash of light. These subtle abnormalities in rod function were similar to those found in asymptomatic heterozygous carriers of the recessive Glu249X mutation. Only one of the 25 heterozygous carriers of the splice site mutation had symptoms and signs of retinitis pigmentosa. CONCLUSIONS: Because 96% of these heterozygous carriers do not have retinitis pigmentosa, it is unlikely that this mutation in intron 4 is a dominant allele. The subtle abnormalities of rod function found in asymptomatic carriers are similar to those found in heterozygous carriers of a recessive rhodopsin allele. The one heterozygous carrier with retinitis pigmentosa probably has a second mutation in the rhodopsin gene or has a defect or defects in another gene that causes his disease.

Adolescent↗
PubMed1995

Red blood cell membrane phosphatidylethanolamine fatty acid content in various forms of retinitis pigmentosa.

In order to test the hypothesis that retinitis pigmentosa (RP) is associated with fatty acid abnormalities within cell membrane phospholipids, red blood cell membrane (RBC) phosphatidylethanolamine (PE) fatty acid content (% of total fatty acids) was measured using high performance liquid chromatography and capillary column gas chromatography in 155 patients from separate families with different genetic types of RP and 101 normal subjects. After controlling for the effects of age and sex, patients with all genetic forms of RP had significantly (P < 0.001) reduced mean RBC PE 22:6 omega 3 (n-3) (docosahexaenoic acid, DHA) content, and significantly (P < 0.001) elevated mean RBC PE dimethyl acetal (DMA) forms of 16:0, 18:0, and 18:1 omega 9 (n-9) as compared with normal subjects. RBC PE content of 22:5 omega 3 (n-3) (a precursor to DHA) and 18:2 omega 6 (n-6) (the major dietary essential fatty acid) were not significantly different in RP than in controls. Analysis by genetic types of RP showed that the mean RBC PE DHA percentages were significantly reduced by 24%, 14%, 30%, and 17%, respectively, in dominant, recessive, X-linked, and isolate forms of RP. The relative amounts of plasmalogens as indicated by DMA forms of 16:0 and 18:0 were significantly (P < 0.01) increased in dominant (by 33% and 25%), recessive (by 36% and 25%), and isolate cases (by 32% and 26%) of RP as compared with normal subjects. No such differences were seen in X-linked cases versus controls. Our data indicate that RBC PE DHA content is decreased in all genetic types of RP patients as compared to control subjects, and that RBC PE plasmalogens are increased in dominant, recessive, and isolate forms of RP. These data raise the possibility that membrane phospholipid fatty acid abnormalities may contribute to the pathogenesis of RP.

Acetals↗
PubMed1995

Clinical expression correlates with location of rhodopsin mutation in dominant retinitis pigmentosa.

PURPOSE: To determine whether severity of retinitis pigmentosa caused by dominant rhodopsin mutations depends on the location altered by the mutation. METHODS: Data from 128 patients (age range, 7 to 73 years), each with 1 to 27 rhodopsin mutations, were analyzed. To approximate normal distributions, visual acuities were converted to ranks and then to the normal form, kinetic visual fields to a V4e test light were converted to equivalent diameters, and dark-adapted sensitivities to an 11 degrees diameter stimulus and electroretinogram (ERG) amplitudes to full-field 0.5-Hz and 30-Hz flashes were converted to common logarithms. Each of these measures was then regressed on age, refractive error (for the ERG), and domain (intradiscal, transmembrane, or cytoplasmic) or codon number of the opsin molecule altered by the mutation. RESULTS: All five measures of function varied significantly with the domain (P < or = 0.0007) or codon number (P < 0.0001) altered by a mutation; visual acuity, visual field diameter, dark-adapted sensitivity, and ERG amplitudes were highest for mutations altering the intradiscal domain or low-numbered codons and lowest for mutations altering the cytoplasmic domain or high-numbered codons. CONCLUSIONS: These data indicate that severity of disease correlates with the location of the amino acid residue altered by a rhodopsin mutation in dominant retinitis pigmentosa.

Adolescent↗
PubMed1994

Digenic retinitis pigmentosa due to mutations at the unlinked peripherin/RDS and ROM1 loci.

In spite of recent advances in identifying genes causing monogenic human disease, very little is known about the genes involved in polygenic disease. Three families were identified with mutations in the unlinked photoreceptor-specific genes ROM1 and peripherin/RDS, in which only double heterozygotes develop retinitis pigmentosa (RP). These findings indicate that the allelic and nonallelic heterogeneity known to be a feature of monogenic RP is complicated further by interactions between unlinked mutations causing digenic RP. Recognition of the inheritance pattern exemplified by these three families might facilitate the identification of other examples of digenic inheritance in human disease.

Alleles↗