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Results for “RETINITIS PIGMENTOSA”

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PubMed2001

[Cloning the differentially expressed genes in the retina of rds mouse during the development of retinitis pigmentosa].

OBJECTIVE: To clone the differentially expressed genes in the retina of rds mouse (the animal model of congenital retinitis pigmentosa) during the disease development. METHODS: The retinal mRNA of rds mouse during the development of retinitis pigmentosa was analyzed by the mRNA differential display. The differentially expressed mRNA fragments were cloned and sequenced. RESULTS: There was obvious difference of gene expression between rds mouse and the control during the development of retinitis pigmentosa. Five differentially expressed bands were cloned and sequenced. One of those had 86% identity (132/154) with the sequence of the human cDNA DKFZp434D1227 from adult testis in GenBank, which was submitted lately (15-Oct-1999) and without much information. The other had lower identity with the sequences in GenBank. A highly expressed clone in the rds mouse on postnatal day 25 had the same length as another clone in the normal on postnatal day 37, which was not expressed in the rds mouse on day 37. The sequences of the two clones were identical in all but two base pairs. CONCLUSION: These results indicate that there are a lot of novel differentially expressed genes in the chronic processing diseases, such as retinitis pigmentosa.

Animals↗

PubMed2005

Effect of exogenous administration of nerve growth factor in the retina of rats with inherited retinitis pigmentosa.

NGF is implicated in retinal damage regression. To study whether this is a direct effect or an effect mediated by NGF on other endogenous biological mediators, we investigated the effect of exogenous administration of NGF in RCS rats affected by retinitis pigmentosa. We found that NGF administration exerts a rescue effect on photoreceptors in this animal model. NGF injection enhances brain-derived neurotrophic factor, beta-fibroblast growth factor, transforming growth factor-beta, vascular endothelial factor and neuropeptide-Y. This suggests that NGF has an effect on RCS rat retina, probably also through the stimulation of other biological mediators produced and released in the retina.

Animals↗

PubMed1985

Synthetic activities of cultured retinal pigment epithelial cells from a patient with retinitis pigmentosa.

We established cultures of retinal pigment epithelial (RPE) cells from four normal individuals and a 56-year-old male patient with autosomal-dominant retinitis pigmentosa (RP) and examined the synthetic activities of these cells via radiolabeling experiments. The uptake of radioactive precursors per milligram of cell protein by RPE cells from the patient with RP was significantly higher than that found in the normal control cells. It appears that the net synthetic activities of glycosaminoglycans and proteins in our patient's cells were enhanced and that the cell metabolism was altered. This finding suggests that malfunctioning of the RPE cells may play a role in the deterioration of photoreceptor functions seen in at least some patients with autosomal-dominant RP.

Adult↗

PubMed1987

A comparative study in the use of closed-circuit television reading machines and optical aids by patients with retinitis pigmentosa and maculopathy.

Patients with retinitis pigmentosa (RP) who have insufficient vision to benefit from optical low vision aids are frequently helped by the closed-circuit television (CCTV) reading machines. RP patients' use of the CCTV is compared with that of patients with maculopathy (i.e. a group with a central scotoma only, is compared to a group which also has additional peripheral field loss), and with that of a "normal" control group. The performance of people with RP is improved by using white print on a black background, while macular degeneration subjects have no significant preference. Speed limits appear to be a function of restrictions imposed by the machine. Both groups frequently read faster with "optical aids".

Adolescent↗

PubMed1996

Linkage of a medium sized Scottish autosomal dominant retinitis pigmentosa family to chromosome 7q.

Retinitis pigmentosa is a group of hereditary retinopathies which is both clinically and genetically heterogeneous. Autosomal dominant (ADRP), autosomal recessive (ARRP), and X linked recessive (XLRP), as well as digenic forms of inheritance have been reported. ADRP has been linked to 3q, 6p, 7p, 7q, 8cen, 17p, 17q, and 19q. Three unrelated ADRP families have been reported to show linkage to 7q. We tested a Scottish ADRP family with microsatellite markers mapping within the 7q31-q35 region, and found three markers (D7S487, D7S514, D7S530) showing statistically significant evidence of linkage. A maximum two point lod score of 3.311 at 0% recombination was obtained for D7S514.

Adolescent↗

PubMed2005

A new locus (RP31) for autosomal dominant retinitis pigmentosa maps to chromosome 9p.

Retinitis pigmentosa (RP) is a debilitating disease of the retina affecting approximately 1.5 million people worldwide. RP shows remarkable heterogeneity both clinically and genetically, with more than 40 genetic loci implicated, 12 of which account for the autosomal dominant form (adRP) of inheritance. We have recently identified a French Canadian family that presents with early onset adRP. After exclusion of all known loci for adRP, a genome-wide search established firm linkage with a marker from the short arm of chromosome 9 (LOD score of 6.3 at recombination fraction theta=0). The linked region is flanked by markers D9S285 and D9S1874, corresponding to a genetic distance of 31 cM, in the region 9p22-p13.

Age of Onset↗

PubMed1995

Rod photoreceptor neurite sprouting in retinitis pigmentosa.

In animal models for retinitis pigmentosa (RP), rod photoreceptors show abnormal distribution of rhodopsin prior to undergoing cell death. To elucidate the steps in degeneration of human photoreceptors, immunocytochemistry was performed on donor retinas from 15 RP patients and five normal subjects. Rhodopsin immunolabeling in the normal retinas was restricted to the rod outer segments. In the RP retinas, rhodopsin was present in shortened rod outer segments and in the surface membranes of the rod inner segments and somata. In regions of photoreceptor death, the surviving rods had sprouted rhodopsin-positive neurites that were closely associated with gliotic Müller cell processes and extended to the inner limiting membrane. Rods and cones in the RP maculas did not form neurites, but the axons of peripheral cones were abnormally elongated and branched. Double immunofluorescence labeling showed that the rod neurites bypassed the horizontal and rod bipolar cells that are normally postsynaptic to rod axons. To our knowledge, this is the first report of rod neurite sprouting in vivo. We were unable to find neurites on degenerate rods in old rds mice, an animal model for RP. The rod neurites in the human RP retinas resemble the long, branched processes formed by rods cultured on Müller cells or purified N-CAM. Neurite growth by surviving rods in the RP retinas may be a response to neurotrophic factor upregulation, loss of inhibitory factors, or changes in molecules associated with reactive Müller cells. Such changes in the retinal microenvironment may impede functional integration of transplanted photoreceptors. The contributions of the rhodopsin-positive rod neurites and abnormal cone axons to the functional abnormalities observed in RP are unknown.

Adult↗

PubMed1999

Acuity recovery and cone pigment regeneration after a bleach in patients with retinitis pigmentosa and rhodopsin mutations.

PURPOSE: To assess visual acuity recovery times and cone photopigment regeneration kinetics after a bleach in the fovea of patients with dominant retinitis pigmentosa due to rhodopsin mutations. METHODS: The authors measured acuity recovery times by computerized photostress testing in 13 patients with dominant retinitis pigmentosa and one of eight rhodopsin mutations. The authors also measured their time constants of cone photopigment regeneration with a video imaging fundus reflectometer to determine whether acuity recovery time depended on pigment regeneration kinetics. These values were compared with those of normal subjects, by the Mann-Whitney U test. The relationship between acuity recovery time and the time constant of cone photopigment regeneration among the patients was quantified by the Spearman rank correlation. RESULTS: The visual acuity recovery times, which averaged 22.0 seconds for the patients with retinitis pigmentosa and 11.2 seconds for the normal subjects, were significantly slower for the patient group (P < 0.001). The time constants of cone pigment regeneration, which averaged 172 seconds for the patients with retinitis pigmentosa and 118 seconds for the normal subjects, also were significantly slower for the patient group (P = 0.043). The authors also found a significant, positive correlation between the visual acuity recovery time and the time constant of pigment regeneration for the patients with retinitis pigmentosa (r = 0.65, P = 0.017). CONCLUSIONS: A slowing of foveal visual acuity recovery and cone pigment regeneration, which are related to each other, can occur in patients with retinitis pigmentosa, due to a rod-specific gene defect.

Adult↗

PubMed1982

Genetic aspects of retinitis pigmentosa in China.

We analyzed 151 pedigrees (209 cases) of retinitis pigmentosa in Shanghai, China. Of the 209 cases, the proportion of autosomal recessive (AR), autosomal dominant (AD), X-linked recessive (XR), and simplex cases is 33.1, 11, 7.7, and 48.3% respectively. The average age of onset was 24.7 years in the AD type, 22.9 years in the AR and five years in the XR type. The average refractive errors were -1.88 D in the AD type, -2.37 D in the AR type, and -5.72 D in the XR type. In addition, 24,100 persons were screened and six cases of retinitis pigmentosa were found. The gene frequencies of the AR (including simplex cases), AD, and XR types as calculated from the disease prevalence were 0.0142267, 0.0000137, and 0.0000384, respectively. The gene frequency of the AR type as calculated from the frequency of consanguinity (15.9%) was 0.00389, which is much less than that calculated from the prevalence. The probable explanation is that the AR type of retinitis pigmentosa really consists of several different disease entities, with each entity representing a separate gene mutation. The number of different mutations within the AR group is estimated to lie between 11 and 41.

Adolescent↗

PubMed2006

Ca2+/recoverin dependent regulation of phosphorylation of the rhodopsin mutant R135L associated with retinitis pigmentosa.

No single molecular mechanism accounts for the effect of mutations in rhodopsin associated with retinitis pigmentosa. Here we report on the specific effect of a Ca2+/recoverin upon phosphorylation of the autosomal dominant retinitis pigmentosa R135L rhodopsin mutant. This mutant shows specific features like impaired G-protein signaling but enhanced phosphorylation in the shut-off process. We now report that R135L hyperphosphorylation by rhodopsin kinase is less efficiently inhibited by Ca2+/recoverin than wild-type rhodopsin. This suggests an involvement of Ca2+/recoverin into the molecular pathogenic effect of the mutation in retinitis pigmentosa which is the cause of rod photoreceptor cell degeneration. This new proposed role of Ca2+/recoverin may be one of the specific features of the proposed new Type III class or rhodopsin mutations associated with retinitis pigmentosa.

Animals↗

PubMed1996

Evaluation of fatty acids in membrane phospholipids of erythrocytes in retinitis pigmentosa patients.

Several investigators have observed abnormalities of plasma DHA in various common forms of retinitis pigmentosa. Erythrocyte membranes are an accessible tissue which may more closely reflect neural membrane fatty acid levels, but little data is yet available on their fatty acid composition in retinitis pigmentosa patients. We have evaluated the DHA levels in red blood cells membrane phospholipids in various genetic forms of retinitis pigmentosa and relative controls. The results obtained indicate significantly lower DHA levels in red blood cell membrane phospholipids in retinitis pigmentosa patients with respect to controls (p < 0.01). This data is significant for autosomal dominant forms only (p < 0.01). Fatty acid content alterations in membrane phospholipids of red blood cells may be considered as markers for abnormalities in the lipid metabolism which disturb the retina integrity.

Adolescent↗

PubMed2005

The association between visual acuity and central retinal thickness in retinitis pigmentosa.

PURPOSE: To determine whether visual acuity is related to central retinal thickness in patients with retinitis pigmentosa. METHODS: Visual acuities were measured with Early Treatment Diabetic Retinopathy Study (ETDRS) charts and optical coherence tomography (OCT3) was used to calculate retinal thicknesses and grade third high-reflectance bands in 162 patients with the typical forms of retinitis pigmentosa who had Snellen visual acuities of 20/20 to 20/200, minimal to no cataracts, and no visible macular cysts. Sixty-five patients were retested within 2 months to estimate the intervisit variability of retinal thickness measurements. RESULTS: ETDRS acuity was best related to retinal thickness measured at fixation and as the average value over the central 1 mm by a second-order polynomial (r(2) = 0.38 and P < 0.001 in both cases). Acuity was maximal for intermediate retinal thickness and appeared to decline for both lesser and greater retinal thicknesses. By linear regression, the decline in acuity for decreasing retinal thickness was steeper in eyes with an absent third high-reflectance band than for eyes with a partially distinct band. No decline was noted in eyes with an intact band. Assessment of intervisit variability of retinal thickness measurements showed 98% confidence limits of +/-17 microm at fixation and +/-11 microm for the central 1 mm. CONCLUSIONS: Both retinal thinning (due to cell loss) and retinal thickening (due to presumed edema) appear to be associated with lower visual acuity in patients with typical retinitis pigmentosa. The definition of the OCT third high-reflectance band may help to predict which patients are more likely to lose visual acuity as retinal thickness declines. An increase or decrease in retinal thickness of more than 17 microm at fixation or 11 microm over the central 1 mm at follow-up can be considered a significant (P < 0.01) change in these patients.

Adolescent↗

PubMed1997

Phenotypes in three Swedish families with X-linked retinitis pigmentosa caused by different mutations in the RPGR gene.

PURPOSE: To assess the clinical phenotypes in three Swedish families with X-linked retinitis pigmentosa caused by different mutations in the RPGR gene. METHODS: Three families from different parts of Sweden, including nine patients with retinitis pigmentosa and six female carriers of X-linked retinitis pigmentosa, were examined clinically. Ophthalmologic examination included kinetic perimetry with a Goldmann perimeter using standardized objects I4e and V4e, dark adaptation final thresholds with a Goldmann-Weeker adaptometer, and full-field electroretinograms. RESULTS: The clinical findings in the patients demonstrated a severe form of retinitis pigmentosa with visual handicap early in life. Patients with a microdeletion of exons 8 through 10 of the RPGR gene had a more severe phenotype compared to the patients with single base-pair mutations in the introns 10 and 13 of the RPGR gene, resulting in splicing defects. Furthermore, heterozygous carriers in these families displayed a wide spectrum of clinical features, from minor symptoms to severe visual disability. CONCLUSION: These three families show a variable clinical phenotype resulting from different mutations in the RPGR gene. A microdeletion spanning at least parts of exons 8 through 10 seems to result in a severe phenotype compared to the splice defects. Heterozygous carriers of X-linked retinitis pigmentosa with these specific RPGR genotypes also show a variability of the phenotype; carriers with the microdeletion may be severely visually handicapped.

Adolescent↗

PubMed1994

Autosomal dominant retinitis pigmentosa caused by the threonine-17-methionine rhodopsin mutation: retinal histopathology and immunocytochemistry.

The retinas from a 68-year-old man with autosomal dominant retinitis pigmentosa caused by the threonine-17-methionine rhodopsin mutation were studied. Patients with this mutation have a characteristic clinical phenotype that shows intra- and interfamilial consistency. The retinas were examined by light and electron microscopy, including immunocytochemistry with markers for rods, cones, the retinal pigment epithelium, the interphotoreceptor matrix and Müller cells, and the results were correlated with those from visual function tests performed fourteen months before death. Grossly, both retinas had heavy deposits of bone spicule-like pigmentation inferiorly, but the superior retinas showed much less pigmentation. The maculas contained no rods and an incomplete monolayer of cone somata, consistent with the patient's severely reduced central vision. The inferior retinas contained no rods and rare cone somata, correlating with an absolute scotoma in the superior field. The superior retinas had near-normal-appearing rods and cones in the far periphery and a gradient from the midperipheral to central retina of progressively shortened outer segments and loss of photoreceptors, consistent with the patient's reduced rod and cone electroretinograms and retained rod and cone sensitivities in the inferior peripheral field by perimetry. Immunocytochemistry with rod-specific markers was qualitatively normal in the superior mid to far peripheral retina. Electron microscopic immunogold labeling with anti-rhodopsin revealed similar densities of gold particles over rod outer segments of the RP and a normal donor retina. Degenerate photoreceptors in the superior equatorial region of the RP retina had short outer segments, and some rods had surface labeling with anti-rhodopsin of the inner segments, somata and synapses. The results indicate regional retinal differences of disease severity in this genotype and that rods in the superior peripheral retina have normal morphology despite the presence of the mutant allele. To the authors' knowledge, this is the first detailed study of rod photoreceptors in the retina of an RP patient with a rhodopsin mutation.

Aged↗

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↗

PubMed1999

Morphometric analysis of the extramacular retina from postmortem eyes with retinitis pigmentosa.

PURPOSE: To evaluate the degree of inner retinal preservation in the extramacular regions of postmortem retinitis pigmentosa (RP) eyes. METHODS: Eighteen RP retinas and 11 age-matched healthy retinas were sectioned for morphometric analysis by light microscopy. The 18 RP retinas were classified by disease severity and mode of inheritance. Cell nuclei in the outer nuclear layer (ONL), inner nuclear layer (INL), and ganglion cell layer (GCL) were counted in adjacent 125-microm segments from an area spanning the region between 4 mm and 10 mm from the fovea. RESULTS: A mixed-effects model showed a decrease in mean cell counts for each of the cell layers when the severity groups and inheritance types compared with those of control retinas. There was no statistically significant difference in the number of nuclei preserved in the INL and GCL in the moderate group compared with the severe group. Results from the INL counts for the different inheritance types of RP showed a higher overall mean percentage of cells was preserved for the autosomal dominant RP (ADRP) group when compared with the X-linked (XLRP) and simplex RP groups. Analysis of the GCL counts revealed significantly more counts only in the ADRP group compared with the XLRP group; the other group comparisons were not significant. CONCLUSIONS: Retinitis pigmentosa results in cell loss in all retinal layers, with the most profound loss in the ONL, followed by the GCL and then the INL. The preservation of the INL and GCL in the extramacular region is less than that previously reported for the macular region of the same retinas.

Aged↗

PubMed1999

Preliminary report: indications of improved visual function after retinal sheet transplantation in retinitis pigmentosa patients.

PURPOSE: To report indications of new visual function after retinal transplantation in two blind patients with retinitis pigmentosa. METHODS: Intact sheets of fetal retina (15 and 17 weeks gestational age) were transplanted subretinally (between the neurosensory retina and the retinal pigment epithelium) near the fovea in the left eye of a 23-year-old white man (Patient A) and in the left eye of a 72-year-old white woman (Patient B), both with autosomal-recessive retinitis pigmentosa. RESULTS: Postoperatively, at 6 and 5 months, respectively, both patients reported new visual sensation in the visual field corresponding to the transplant. In both patients, the visual sensation continued to be present after transplantation, at 12 and 8 months, respectively. In Patient A, a transient multifocal electroretinography (mfERG) response was observed in the transplant area 4 months postoperatively but was not detectable in Patient A at 6.0 and 9.5 months post-retinal transplantation. In Patient B, no positive mfERG responses were seen up to 5 months postoperatively. No rejection (presenting as cystoid macular edema, macular pucker, and extensive intraretinal edema with disrupted retinal pigment epithelium) to the transplanted tissue was seen up to 13 months in Patient A and 9 months in Patient B by fluorescein angiography. CONCLUSION: Transplantation of intact sheets of fetal human retina in two patients with retinitis pigmentosa was not associated with evidence of transplant rejection. Subjective improvement and an indication of objective improvement 4 months postoperatively were seen in Patient A, and subjective improvement only was seen in Patient B.

Adult↗

PubMed1992

Activated retinitis pigmentosa peripheral lymphocytes adhere to and alter cultured human retinal pigment epithelial cells.

Interleukin-2 receptor (IL-2R) is an activation molecule that, when expressed on peripheral blood lymphocyte (PBL) membranes, indicates the secretion of IL-2 and initiation of an immune system activation cascade. Comparing the average of IL-2R expression in 34 patients with retinitis pigmentosa (RP) syndrome (561 +/- 282 cells/mm3; mean +/- standard deviation) with 35 age-matched normal subjects (194 +/- 39 cells/mm3), it was found that those with RP had greater numbers of IL-2R-positive cells (P less than 0.001). The increased amounts of IL-2R on PBL of 29 RP and the homotypic self-aggregation of RP PBL by phase and scanning electron microscopy led to the study of the interaction of RP PBL with cultured human postmortem retinal pigment epithelial cells (RPE). A direct correlation was found between the amount of IL-2R expression and the numbers of RP lymphocytes adhering to RPE monolayers. However, the adherence effect was not unique to RP syndrome but appeared to be a nonspecific result of lymphocyte activation. Greater adherence to RPE than normal also was observed in PBL from disease control subjects with elevated IL-2R values and in PBL stimulated by the mitogen, concanavalin A (Con-A). In addition, RPE monolayers were destroyed by Con-A-stimulated PBL that showed 95-98% IL-2R expression. Similar, but less serious effects, occurring in RPE cells after 1 wk's cocultivation with RP PBL, suggested that activated RP lymphocytes can be cytotoxic to RPE during prolonged contact. Because macrophage-like cells and class II major histocompatibility complex expression have been found in RP-affected retinas, immune-mediated cytopathologic effects may contribute to retinal degeneration in RP.

Adolescent↗