SEARCH · PubMed Health

Results for “RETINITIS PIGMENTOSA”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15Linked to original sources

PubMed1998

Arrestin gene mutations in autosomal recessive retinitis pigmentosa.

OBJECTIVE: To assess the clinical and molecular genetic studies of patients with autosomal recessive retinitis pigmentosa associated with a mutation in the arrestin gene. DESIGN: Results of molecular genetic screening and case reports with DNA analysis and clinical features. SETTING: University medical center. PATIENTS: One hundred twenty anamnestically unrelated patients with autosomal recessive retinitis pigmentosa. METHODS: DNA analysis was performed by single strand conformation polymorphism followed by nucleotide sequencing to search for a mutation in exon 11 of the arrestin gene. Clinical features were characterized by visual acuity slitlamp biomicroscopy, fundus examinations, fluorescein angiography, kinetic visual field testing, and electroretinography. RESULTS: We identified 3 unrelated patients with retinitis pigmentosa associated with a homozygous 1-base-pair deletion mutation in codon 309 of the arrestin gene designated as 1147delA. All 3 patients showed pigmentary retinal degeneration in the midperipheral area with or without macular involvement. Patient 1 had a sibling with Oguchi disease associated with the same mutation. Patient 2 demonstrated pigmentary retinal degeneration associated with a golden-yellow reflex in the peripheral fundus. Patients 1 and 3 showed features of retinitis pigmentosa without the golden-yellow fundus reflex. CONCLUSIONS: Although the arrestin 1147delA has been known as a frequent cause of Oguchi disease, this mutation also may be related to the pathogenesis of autosomal recessive retinitis pigmentosa. This phenomenon may provide evidence of variable expressivity of the mutation in the arrestin gene.

Adult↗

PubMed1996

Retinal hemodynamics in retinitis pigmentosa.

PURPOSE: To investigate the retinal hemodynamic changes occurring in patients with retinitis pigmentosa (RP). METHODS: Bidirectional laser Doppler velocimetry and monochromatic fundus photography were used to determine retinal venous diameter (D), maximum erythrocyte velocity (Vmax), and volumetric blood flow (Q) in the major retinal veins of eight patients with RP and eight age-matched normal controls. The retinal vascular regulatory responses to hyperoxia, defined as the percent decreases in D (RD), Vmax (RVmax), and Q (RQ) at four to six minutes of breathing 100% oxygen, were determined in eight normal subjects and five RP patients. RESULTS: Average D, Vmax, and Q +/- S.D. in the largest retinal vein of each subject were 106 +/- 14 microns, 1.01 +/- 0.20 cm/sec, and 3.5 +/- 1.3 microliters/min, respectively, in RP patients, and 166 +/- 12 microns, 1.79 +/- 0.14 cm/sec, and 14.7 +/- 2.6 microliters/min, respectively, in normal subjects. This corresponded to significant decreases from normal of 36% in D, 44% in Vmax, and 76% in Q in RP patients (Wilcoxon's rank sum test, P < .001). Average total retinal volumetric blood flow rate was 8.2 +/- 2.9 microliters/min in RP patients and 37 +/- 4.9 microliters/min in normal subjects, corresponding to a significant decrease from normal of 78% (Wilcoxon's rank sum test, P < .001). In RP patients, the regulatory responses to hyperoxia (RD, RVmax, and RQ) were similar to those observed in normal subjects. RESULTS: Retinal blood flow is significantly decreased in patients with RP, probably as a result of vascular remodeling in response to reduced metabolic demand. The regulatory responses to hyperoxia are similar to those of normal subjects. Measurements of retinal blood flow may help assess the progression of the disease and the effects of treatment.

Adult↗

PubMed1978

Rhodopsin and visual threshold in retinitis pigmentosa.

Rhodopsin kinetics and visual threshold were determined in three subjects with a dominant form of retinitis pigmentosa. The retinal areas studied showed varying loss of sensitivity, which correlated well with the reduction in the measured density of rhodopsin in the test region. Rhodopsin photosensitivity was normal, and there was no evidence that either rhodopsin or the cone pigments regenerated more rapidly than normal. The findings in these cases of retinitis pigmentosa, when compared with the threshold changes induced by vitamin A deficiency or photic bleaching, suggest that the disease produces an imbalance between disc removal and new disc formation, which results in a progressive shortening of the photoreceptor outer segments and, eventually, in their complete disappearance.

Adult↗

PubMed2002

Progressive photoreceptor degeneration, outer segment dysplasia, and rhodopsin mislocalization in mice with targeted disruption of the retinitis pigmentosa-1 (Rp1) gene.

Retinitis pigmentosa (RP), a common group of human retinopathic diseases, is characterized by late-onset night blindness, loss of peripheral vision, and diminished or absent electroretinogram (ERG) responses. Mutations in the photoreceptor-specific gene RP1 account for 5-10% of cases of autosomal dominant RP. We generated a mouse model of the RP1 form of RP by targeted disruption of the mouse ortholog (Rp1) of human RP1. In Rp1(-/-) mice, the number of rod photoreceptors decreased progressively over a period of 1 year, whereas that of cone photoreceptors did not change for at least 10 months. Light and electron microscopic analysis revealed that outer segments of Rp1(-/-) rods and cones were morphologically abnormal and became progressively shorter in length. Before photoreceptor cell death, rhodopsin was mislocalized in inner segments and cell bodies of Rp1(-/-) rods. Rod ERG amplitudes of Rp1(-/-) mice were significantly smaller than those of Rp1(+/+) mice over a period of 12 months, whereas those of Rp1(+/-) mice were intermediate. The decreases in cone ERG amplitudes were slower and less severe than those in rods. These findings demonstrate that Rp1 is required for normal morphogenesis of photoreceptor outer segments and also may play a role in rhodopsin transport to the outer segments. The phenotype of Rp1 mutant mice resembles the human RP1 disease. Thus, these mice provide a useful model for studies of RP1 function, disease pathology, and therapeutic interventions.

Animals↗

PubMedDate not supplied

Retinitis pigmentosa: defined from a molecular point of view.

Retinitis pigmentosa (RP) denotes a group of hereditary retinal dystrophies, characterized by the early onset of night blindness followed by a progressive loss of the visual field. The primary defect underlying RP affects the function of the rod photoreceptor cell, and, subsequently, mostly unknown molecular and cellular mechanisms trigger the apoptotic degeneration of these photoreceptor cells. Retinitis pigmentosa is very heterogeneous, both phenotypically and genetically. In this review we propose a tentative classification of RP based on the functional systems affected by the mutated proteins. This classification connects the variety of phenotypes to the mutations and segregation patterns observed in RP. Current progress in the identification of the molecular defects underlying RP reveals that at least three distinct functional mechanisms may be affected: 1) the daily renewal and shedding of the photoreceptor outer segments, 2) the visual transduction cascade, and 3) the retinol (vitamin A) metabolism. The first group includes the rhodopsin and peripherin/RDS genes, and mutations in these genes often result in a dominant phenotype. The second group is predominantly associated with a recessive phenotype that results, as we argue, from continuous inactivation of the transduction pathway. Disturbances in the retinal metabolism seem to be associated with equal rod and cone involvement and the presence of deposits in the retinal pigment epithelium.

Apoptosis↗

PubMed1992

Serum transferrin in patients with retinitis pigmentosa.

The CDG syndrome is a newly detected disorder with a carbohydrate defect in glycoproteins such as transferrin. As retinitis pigmentosa is a part of this syndrome, there could also be other subtypes of retinitis pigmentosa with a similar biochemical defect. Isoforms of serum transferrin were therefore analysed in 78 patients from different families with retinitis pigmentosa and showed slightly or moderately elevated values for less glycosylated isoforms in two families. The study suggests that abnormal glycoprotein metabolism manifested by elevated values of carbohydrate-deficient isotransferrins may be present in a small proportion of families with retinitis pigmentosa. The relationship between the glycoprotein defect and retinitis pigmentosa remains to be established.

Adult↗

PubMed2006

A novel missense RP1 mutation in retinitis pigmentosa.

AIMS: More than 20 mutations associated with retinitis pigmentosa (RP) have been identified in the retinitis pigmentosa 1 (RP1) gene, all of them leading to the production of a truncated protein without 50-70% of the C-terminal of the RP1 protein. RP1 was recently found to be a microtubule-associated protein (MAP) and responsible for the organisation of the photoreceptor outer segment. The N-terminal doublecortin (DCX) domain of RP1 is essential for its function. But how the C-terminal of the protein affects its function is still not known. This study aims to get a better understanding of the RP1 gene by mutation screening on RP patients. METHODS: Peripheral blood was taken from 72 RP patients. Together with 101 RP patients and 190 control subjects previously reported, mutation screening was performed by polymerase chain reaction (PCR) and direct sequencing. Statistical analysis was performed using SPSS. RESULTS: Two novel missense sequence changes, D984G and C727W, and one novel variant, 6492T>G, at the 3' untranslated region were found. They were not found in 190 control subjects. D984G causes RP. It creates two possible N-myristoylation sites according to PROSITE. C727W does not segregate with RP in the family. It abolishes an N-myristoylation site. R872H, a previously reported polymorphism, was predominantly present in control subjects (P=0.001). CONCLUSIONS: Our results suggest that disruption of the C-terminal of RP1 may be associated with the development of RP, and the possible involvement of the RP1 polypeptide downstream of its DCX domain in normal RP1 function.

Adult↗

PubMed1984

Transport of fluorescein in the ocular posterior segment in retinitis pigmentosa.

The function of the blood-retinal barrier was assessed by vitreous fluorophotometry in 12 patients with various genetic types of retinitis pigmentosa and in 11 normal subjects. The measurements were corrected to minimize the effect of artifacts. We evaluated the inward penetration of fluorescein sodium across the blood-retinal barrier and determined the outward permeability coefficient for fluorescein by interpreting the data with a pharmacokinetic computer model. Patients with retinitis pigmentosa had increased inward permeability and decreased outward permeability to fluorescein in comparison with values of normal subjects.

Adolescent↗

PubMed1982

Pathology of retinitis pigmentosa.

Eyes from patients with retinitis pigmentosa were obtained at autopsy. They were processed in celloidin and examined by light microscopy. The earliest evidence of retinal degeneration occurred in the equatorial zone and then extended peripherally and centrally. In the eyes with the earliest involvement, a sequence could be demonstrated in the zone of transition from the less involved macula to the more degenerated retina at the equator. The probable order for the development of degenerative changes in our material appeared to be as follows: (1) migration of nuclei from the outer nuclear layer to the rod and cone layer and the outer plexiform layer; (2) degeneration and loss of photoreceptors and their nuclei in the outer nuclear layer; (3) loss of connecting fibers in the outer plexiform layer; (4) migration of the retinal pigment epithelium (RPE) into the retina, mainly around the blood vessels, but also as isolated balls and spots (this prominent feature, which characterizes the disease, is secondary and only follows the loss of the photoreceptors and their nuclei); (5) adhesion of the retinal to the retinal pigment epithelium or Bruch's membrane in spots or broad areas and; (6) possible transneuronal degeneration of some cells in the inner nuclear and ganglion cell layers. Gliosis of the disc was universal as was the presence of glial membranes from the disc extending over the posterior retina, especially prominent in the macular region. As the material was obtained from 16 to 35 years ago, we lack electrophysiologic and familial data and electron microscopy was not possible.

Adult↗

PubMedDate not supplied

Retinitis pigmentosa, Coats disease and uveitis.

PURPOSE: To study the anamnestic immune response to retinal specific antigens of two patients suffering from a rare triad of retinitis pigmentosa, Coats disease and uveitis. PATIENTS: 17-year-old girl presented with an acute episode of panuveitis, and her 19-year-old brother suffered from chronic uveitis. On examination, both patients showed retinal vascular changes and subretinal exudations typical of Coats disease, with bone-spicule pigmentary changes as observed in retinitis pigmentosa. RESULTS: All routine examinations were unrevealing. However, the peripheral lymphocytes from these two siblings gave a specific anamnestic response to retinal antigens in vitro. A stimulation index of 4.6 was obtained when the sister's lymphocytes were stimulated with interphotoreceptor binding protein, IRBP--during the acute stage of the uveitis. The brother's lymphocytes showed a stimulation index of 2.7 towards S-Ag during the chronic phase of his uveitic condition. CONCLUSIONS: These results indicate that autoimmunity towards retinal antigens may play some role in specific types of retinitis pigmentosa. Whether these autoimmune reactions are a primary pathological mechanism or are secondary to the extensive destruction of the photoreceptor layer resulting from the retinitis pigmentosa remains debatable.

Adolescent↗

PubMedDate not supplied

Prevalence of retinitis pigmentosa in urban and rural adult Chinese: The Beijing Eye Study.

PURPOSE: To determine the prevalence of retinitis pigmentosa in the elderly Chinese population. METHODS: The Beijing Eye Study is a population-based, cross-sectional cohort study and included 4439 subjects out of 5324 subjects invited to participate (response rate 83.4%) with an age of 40+ years. Readable fundus photographs were available for 4027 (90.7%) subjects. Diagnostic criteria for retinitis pigmentosa were visual field defects on frequency doubling perimetry, typical ophthalmoscopic abnormalities such as retinal pigment deposits, retinal arteriole attenuation, and pigment epithelial atrophy, and no other reason for perimetric defects and fundus abnormalities. RESULTS: Retinitis pigmentosa was diagnosed in four subjects (all men). Its prevalence was 0.099+/-3.15% (95% CI: 0.00, 0.2). CONCLUSIONS: Retinitis pigmentosa with typical fundus appearance and functional loss may be present in about 1 out of 1000 elderly Chinese in Northern China. Calculated for the whole population in China, the figure would be 1.3 million patients with retinitis pigmentosa.

Adult↗

PubMed2004

[Progress in pathogenesis and therapeutic research in retinitis pigmentosa and age-related macular degeneration].

Retinitis pigmentosa (RP) and age-related macular degeneration (AMD) are designated special targeted eye diseases by the Welfare and Labor Ministry of Japan. We have been studying the pathogenesis, diagnosis, treatment, and evaluation of these diseases. The development of molecular genetic analyses of RP revealed that the type and frequency of mutations varied with the ethnic population. In our present study, we focused on the genetic analysis and clinical examinations for autosomal dominant retinitis pigmentosa (ADRP). We screened 96 unrelated ADRP families with 9 genes, which included rhodopsin, peripherin/RDS, RP 1, NRL, FSCN 2, PRPF 31, PRPC 8, HPRP 3, IMPDH 1. We also showed the correlations we have found between the phenotype and genotype of hereditary retinal diseases in Japanese patients. Our mutation screenings suggested that Japanese patients with ADRP might have a unique mutation, because the mutation in the FSCN 2 gene has been found only in Japanese patients. On the other hand, the Pro347Leu and Pro23His mutations in the rhodopsin, the Arg677X mutation in the RP 1, and the Asp226Asn mutation in the IMPDH 1 genes are representative mutations for ADRP, and are not found or are very rare in Japanese patients with ADRP. The results of randomized controlled trials of low-dose radiation for wet-type age-related macular degeneration located at the fovea centralis indicate the effectiveness of this treatment for maintaining visual acuity and regression of choroidal neovascular membrane (CNV) for at least one-year. Simple surgical removal of CNV or transplantation of autologous cultured iris pigment epithelium (IPE) with vitreous surgery showed some improvement of vision. In either RP or AMD, photoreceptors die, in most cases by apoptosis. Neurotrophic factors (NT) are effective for reducing these processes and preventing photoreceptor cell death in animal models. To apply these methods to humans, the procedures are as follows: 1) obtaining IPE by peripheral iridectomy, 2) culturing it with autologous serum and transfecting the cDNA of NT, and then 3) transplantation of these cells under the retina. We used cDNA of brain-derived neurotrophic factor (BDNF) with adeno-associated virus (AAV) as a vector. These ex vivo procedures were safe and very effective for preventing photoreceptor cell death in animal models, such as RCS rats and light-damaged rats. In the future, these procedures could be applied for RP or AMD and might show some clinical effects for maintaining or improving the vision of patients.

Aging↗

PubMed1993

A new codon 15 rhodopsin gene mutation in autosomal dominant retinitis pigmentosa is associated with sectorial disease.

OBJECTIVE: To ascertain and characterize rhodopsin gene mutations in autosomal dominant retinitis pigmentosa and to correlate these mutations with the clinical phenotypes. METHODS: DNA was extracted from leukocytes, and the rhodopsin gene was amplified and analyzed using molecular-biological methods. Clinical and electrophysiological data were collected from patient charts. RESULTS: We found a disease-causing mutation that was previously undescribed, to our knowledge, for autosomal dominant retinitis pigmentosa within codon 15 of exon 1 of the rhodopsin gene. It was a single base-pair transversion (AAT to AGT) leading to a serine-for-asparagine substitution. This altered a glycosylation site in the intradiscal portion of the rhodopsin molecule. The pedigree examined demonstrated an inferior distribution of retinal pigmentary changes and predominantly superior visual field loss with relative preservation of electroretinographic amplitudes and good vision, which is consistent with sectorial or sectorial-like retinitis pigmentosa. CONCLUSIONS: A codon 15 rhodopsin gene mutation caused retinitis pigmentosa in the pedigree studied. There may be an association between intradiscal rhodopsin gene mutations and sectorial forms of retinitis pigmentosa.

Adult↗

PubMed2005

Sequence variations in the retinal fascin FSCN2 gene in a Spanish population with autosomal dominant retinitis pigmentosa or macular degeneration.

PURPOSE: Only one mutation in the retinal fascin gene (FSCN2) has so far been associated with autosomal dominant retinitis pigmentosa (adRP) and macular dystrophy (adMD), in a Japanese population. Our study was designed to identify mutations in the FSCN2 gene among Spanish persons with adRP or adMD. METHODS: Denaturing gradient gel electrophoresis and direct genomic sequencing were used to evaluate the complete coding region and flanking intronic sequences of the FSCN2 gene for mutations in 150 unrelated adRP and 15 adMD index patients, and in 50 sporadic cases of retinitis pigmentosa, together with 50 controls. Ophthalmic and electrophysiological examination of retinitis pigmentosa patients and their relatives was carried out according to pre-existing protocols. RESULTS: Sixteen nucleotide substitutions were detected in the coding sequence of the index patients. Nine of these, His7Tyr, Ala122Thr, Ser126Phe, His138Tyr, Arg149Gln, Ala240Thr, Ala323Thr, Asn331His, and Phe367Leu are missense mutations, one is a nonsense mutation (Lys302Stop), and six are silent mutations. Co-segregation of the mutations in the families showed no direct relation between mutation and disease. CONCLUSIONS: The photoreceptor-specific FSCN2 gene showed a relatively high number of sequence variations. The mutation 208delG in FSCN2, the only mutation so far associated with adRP or adMD, and which presumably causes a null allele, was not detected in these Spanish families. The nonsense mutation, Lys302Stop, detected in one adRP Spanish family is not the cause of the disease. These findings support the fact that the kind and frequency of the mutations depend on the ethnic population.

Amino Acid Sequence↗

PubMed1993

Colour vision in retinitis pigmentosa. Influence of cystoid macular edema.

In retinitis pigmentosa patients the effect of cystoid macular edema on colour vision was studied. The occurrence of cystoid macular edema decreases with increasing colour vision defect. The mutual proportion of the main types of colour vision defects remains stable until visual acuity has dropped to 0.5; at lower VA levels the number of red-green defects increases. Neither the finding of a blue-yellow colour vision defect in FM100 Hue testing nor the appearance of anomaloscopic pseudoprotanomaly is influenced by cystoid macular edema. The authors conclude that cystoid macular edema in retinitis pigmentosa patients mainly affects visual acuity and not colour vision. They also noted a familial occurrence of cystoid macular edema.

Color Perception↗

PubMed2004

Autosomal recessive retinitis pigmentosa in a Pakistani family mapped to CNGA1 with identification of a novel mutation.

PURPOSE: To map the locus for autosomal recessive retinitis pigmentosa in a large Pakistani family and to determine the causative mutation. METHODS: A large family with multiple individuals affected by autosomal recessive retinitis pigmentosa was ascertained in the Punjab province of Pakistan as part of an ongoing project between the CEMB, Lahore, Pakistan and the NEI to identify genetic causes of eye diseases. After initial analysis of previously identified autosomal recessive retinitis pigmentosa loci, a genome wide scan was performed using microsatellite markers at about 10 cM intervals. Two point lod scores were calculated and haplotypes were analyzed in order to define disease locus. Bidirectional dideoxynucleotide sequencing was used to screen for mutations in candidate genes. RESULTS: In the genome wide scan, autosomal recessive retinitis pigmentosa in this Pakistani family showed linkage to an 11.7 cM region of chromosome 4p12 between D4S405 and D4S1592 with a maximum lod score of 2.90 with D4S405 at theta;=0.01 Sequence analysis of CNGA1 identified a 2 bp deletion in exon 8: c.626_627delTA resulting in a frameshift, p.Ser209fsX26 in the translated protein. This mutation results in deletion of the COOH terminal 482 of 690 total amino acids in CNGA1 and their replacement by 25 novel amino acids before a premature termination. The mutation is found in a homozygous state in all 7 affected individuals and was heterozygous in all 15 unaffected family members examined. The mutant allele of CNGA1 itself shows linkage to the disease with maximum lod score of 4.43 at theta;=0. CONCLUSIONS: The autosomal recessive retinitis pigmentosa in this family is caused by a mutation in CNGA1 gene. To our knowledge, this is the first report in which both linkage analysis and identification of a mutation support CNGA1 as a cause for autosomal recessive retinitis pigmentosa.

Base Sequence↗

PubMed1987

Electroretinographic findings in retinitis pigmentosa.

Full-field electroretinograms (ERGs) provide a basis for establishing the diagnosis of widespread progressive forms of retinitis pigmentosa in early life even at a time when fundus abnormalities visible with the ophthalmoscope are minimal or absent. Patients characteristically show delays in rod or cone b-wave implicit times or both, while patients with self-limited sector retinitis pigmentosa or stationary night blindness have normal b-wave implicit times. ERGs are presented to show their usefulness in detection of female carriers of X-chromosome-linked retinitis pigmentosa, in quantitating the natural course of all types of retinitis pigmentosa, and in detecting an abnormal rod ERG diurnal rhythm in the dominant form. Potential therapies for the retinitis pigmentosa associated with abetalipoproteinemia and Refsum's disease are also considered.

Abetalipoproteinemia↗

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↗