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Sample records for retinitis pigmentosa patients

  1. Retinitis Pigmentosa

    MedlinePlus

    ... Action You are here Home › Retinal Diseases Listen Retinitis Pigmentosa What is retinitis pigmentosa? What are the symptoms? ... is available? What treatment is available? What is retinitis pigmentosa? Retinitis pigmentosa, also known as RP, refers to ...

  2. Retinitis pigmentosa

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/001029.htm Retinitis pigmentosa To use the sharing features on this page, please enable JavaScript. Retinitis pigmentosa is an eye disease in which there is ...

  3. [Visual rehabilitation in patients with retinitis pigmentosa].

    PubMed

    de Castro, Celina Tamaki Monteiro; Berezovsky, Adriana; de Castro, Danilo Dimas Monteiro; Salomão, Solange Rios

    2006-01-01

    To determine which low-vision aids could be useful to patients with retinitis pigmentosa and also the benefits that the rehabilitation program could provide based on visual acuity and/or daily visual tasks. A group of 30 patients with retinitis pigmentosa aged from 7 to 73 years were enrolled in this study. Visual acuity and visual function tests (visual field, full-field electroretinogram) was performed and low-vision aids tested. Information about the use of the remaining vision was obtained. After choosing the best optical or electronic devices and before their prescription, a low-vision training program was carried out. The best corrected visual acuity varied from HM (hand movements) to 20/40 for distance and visual acuity better than 16M to 0.5M for near. 90% of the patients had optical devices prescribed: 13 for near, 9 for distance, 2 electronic devices and 3 filters. Three patients with extremely narrow visual field and very low visual acuity were referred to orientation and mobility. The low-vision aids were useful for the retinitis pigmentosa patients: telescopes, hand-held magnifiers, stand magnifiers, half-eye base-in prism lenses, electronic devices and illumination control were beneficial to enhance visual acuity and visual efficiency. The prescription of low-vision aids was helpful in daily-life activities and a high level of satisfaction with the implemented visual rehabilitation program was reported.

  4. Retinitis Pigmentosa.

    ERIC Educational Resources Information Center

    Carr, Ronald E.

    1979-01-01

    The author describes the etiology of retinitis pigmentosa, a visual dysfunction which results from progressive loss of the retinal photoreceptors. Sections address signs and symptoms, ancillary findings, heredity, clinical diagnosis, therapy, and research. (SBH)

  5. Retinitis Pigmentosa.

    ERIC Educational Resources Information Center

    Carr, Ronald E.

    1979-01-01

    The author describes the etiology of retinitis pigmentosa, a visual dysfunction which results from progressive loss of the retinal photoreceptors. Sections address signs and symptoms, ancillary findings, heredity, clinical diagnosis, therapy, and research. (SBH)

  6. Diagnostic imaging in patients with retinitis pigmentosa.

    PubMed

    Mitamura, Yoshinori; Mitamura-Aizawa, Sayaka; Nagasawa, Toshihiko; Katome, Takashi; Eguchi, Hiroshi; Naito, Takeshi

    2012-01-01

    Retinitis pigmentosa (RP) is a progressive inherited retinal disease, and patients with RP have reduced visual function caused by a degeneration of the photoreceptors and retinal pigment epithelium (RPE). At the end stage of RP, the degeneration of the photoreceptors in the fovea reduces central vision, and RP is one of the main causes of acquired blindness in developed countries. Therefore, morphological and functional assessments of the photoreceptors in the macula area can be useful in estimating the residual retinal function in RP patients. Optical coherence tomography (OCT) is a well-established method of examining the retinal architecture in situ. The photoreceptor inner/outer segment (IS/OS) junction is observed as a distinct, highly reflective line by OCT. The presence of the IS/OS junction in the OCT images is essential for normal visual function. Fundus autofluorescence (FAF) results from the accumulation of lipofuscin in the RPE cells and has been used to investigate RPE and retinal function. More than one-half of RP patients have an abnormally high density parafoveal FAF ring (AF ring). The AF ring represents the border between functional and dysfunctional retina. In this review, we shall summarize recent progress on diagnostic imaging in eyes with RP.

  7. Increased Prevalence of Flammer Syndrome in Patients with Retinitis Pigmentosa.

    PubMed

    Konieczka, K; Koch, S; Schoetzau, A; Todorova, M G

    2016-04-01

    "Retinitis pigmentosa" refers to a group of degenerative eye diseases with a genetic background. Flammer syndrome encompasses a set of symptoms and signs, mainly but not exclusively related to dysregulation of blood vessels. The purpose of the present study was to determine, with the help of a questionnaire, whether symptoms of Flammer syndrome occur more often in patients with retinitis pigmentosa than in controls. 76 patients with retinitis pigmentosa (members of the Swiss patient organization for retinitis pigmentosa) and 274 control subjects answered a questionnaire (Flammer Syndrome Questionnaire) on 15 symptoms and signs of Flammer syndrome. Seven of 15 symptoms and signs of Flammer syndrome were significantly more often positive in retinitis pigmentosa patients than in controls. Six additional symptoms and signs occurred non-significantly more often and 2 non-significantly less often in patients with retinitis pigmentosa. Retinitis pigmentosa patients suffer significantly more often from symptoms and signs of the Flammer syndrome than control subjects. This includes low body mass index, low blood pressure, feeling cold, migraine, increased smell perception and perfectionism. The reason for this association between retinitis pigmentosa and Flammer syndrome and the potential implications need to be determined. Georg Thieme Verlag KG Stuttgart · New York.

  8. Vitreous cysts in patients with retinitis pigmentosa.

    PubMed

    Yoshida, Noriko; Ikeda, Yasuhiro; Murakami, Yusuke; Nakatake, Shunji; Tachibana, Takashi; Notomi, Shoji; Hisatomi, Toshio; Ishibashi, Tatsuro

    2015-11-01

    To determine the prevalence of vitreous cysts in patients with retinitis pigmentosa (RP). We retrospectively reviewed the charts of 435 consecutive patients diagnosed as having typical RP. Vitreous cysts were diagnosed in 37 eyes of 28 patients with RP (13 males and 15 females; mean age 47.0 ± 19.8 years; range 15-79 years), for an overall prevalence of 6.4%. The cysts were observed bilaterally in nine of the patients (32.1%). Among these 28 patients, 11 (39.3%) were younger than 40 years. In all, 81.8% of the vitreous cysts were detected around the optic nerve head. We demonstrated that the prevalence of vitreous cysts was 6.4% in patients with RP. These cysts were considered to be asymptomatic.

  9. Retinitis pigmentosa

    PubMed Central

    Hamel, Christian

    2006-01-01

    Retinitis pigmentosa (RP) is an inherited retinal dystrophy caused by the loss of photoreceptors and characterized by retinal pigment deposits visible on fundus examination. Prevalence of non syndromic RP is approximately 1/4,000. The most common form of RP is a rod-cone dystrophy, in which the first symptom is night blindness, followed by the progressive loss in the peripheral visual field in daylight, and eventually leading to blindness after several decades. Some extreme cases may have a rapid evolution over two decades or a slow progression that never leads to blindness. In some cases, the clinical presentation is a cone-rod dystrophy, in which the decrease in visual acuity predominates over the visual field loss. RP is usually non syndromic but there are also many syndromic forms, the most frequent being Usher syndrome. To date, 45 causative genes/loci have been identified in non syndromic RP (for the autosomal dominant, autosomal recessive, X-linked, and digenic forms). Clinical diagnosis is based on the presence of night blindness and peripheral visual field defects, lesions in the fundus, hypovolted electroretinogram traces, and progressive worsening of these signs. Molecular diagnosis can be made for some genes, but is not usually performed due to the tremendous genetic heterogeneity of the disease. Genetic counseling is always advised. Currently, there is no therapy that stops the evolution of the disease or restores the vision, so the visual prognosis is poor. The therapeutic approach is restricted to slowing down the degenerative process by sunlight protection and vitaminotherapy, treating the complications (cataract and macular edema), and helping patients to cope with the social and psychological impact of blindness. However, new therapeutic strategies are emerging from intensive research (gene therapy, neuroprotection, retinal prosthesis). PMID:17032466

  10. Evaluation of contrast visual acuity in patients with retinitis pigmentosa.

    PubMed

    Oomachi, Kazumi; Ogata, Kazuha; Sugawara, Takeshi; Hagiwara, Akira; Hata, Akira; Yamamoto, Shuichi

    2011-01-01

    The purpose of this study was to determine visual acuity at different contrast levels under photopic and mesopic conditions in patients with retinitis pigmentosa. Sixty eyes of 31 normal controls, 92 eyes of 52 patients with retinitis pigmentosa without other ocular disorders (RP-1 group), and 20 eyes of 14 patients with retinitis pigmentosa with cataracts and without other ocular disorders (RP-2 group) were studied. Conventional visual acuity was measured using a conventional Landolt ring chart with 100% contrast and luminance of 150 cd/m(2). All of the patients with retinitis pigmentosa had a decimal visual acuity better than 1.0. Contrast visual acuity was measured with the same Landolt ring chart with contrasts of 100% and 10% and under photopic (200 cd/m(2)) and mesopic (10 cd/m(2)) conditions. Decimal visual acuities were converted to logMAR units for the analyses. The 100% contrast visual acuity and the 10% contrast visual acuity determined under both photopic and mesopic conditions were significantly poorer in both the RP-1 and RP-2 groups than in the controls. The differences between the conventional visual acuity and the 100% contrast visual acuity were significantly greater in the RP-1 and RP-2 groups than in the controls under both photopic and mesopic conditions. The differences between the 100% contrast visual acuity and the 10% contrast visual acuity were not significant among the three groups under photopic and mesopic conditions. Contrast visual acuities were greatly reduced in patients with retinitis pigmentosa with relatively well preserved conventional visual acuity, and the contrast visual acuity was largely influenced by ambient light levels in patients with retinitis pigmentosa. Although a longitudinal study for confirmation has to be performed, our findings indicate that contrast visual acuity is a better test to follow changes in visual function in patients with retinitis pigmentosa.

  11. Gene panel sequencing in Brazilian patients with retinitis pigmentosa.

    PubMed

    Costa, Kárita Antunes; Salles, Mariana Vallim; Whitebirch, Chris; Chiang, John; Sallum, Juliana Maria Ferraz

    2017-01-01

    Retinal dystrophies constitute a group of diseases characterized by clinical variability and pronounced genetic heterogeneity. Retinitis pigmentosa is the most common subtype of hereditary retinal dystrophy and is characterized by a progressive loss of peripheral field vision (Tunnel Vision), eventual loss of central vision, and progressive night blindness. The characteristics of the fundus changes include bone-spicule formations, attenuated blood vessels, reduced and/or abnormal electroretinograms, changes in structure imaged by optical coherence tomography, and subjective changes in visual function. The different syndromic and nonsyndromic forms of retinal dystrophies can be attributed to mutations in more than 250 genes. Molecular diagnosis for patients with retinitis pigmentosa has been hampered by extreme genetic and clinical heterogeneity between retinitis pigmentosa and other forms of retinal dystrophies. Next generation sequencing (NGS) technologies are among the most promising techniques to identify pathogenic variations in retinal dystrophies. The purpose of this study was to discover the molecular diagnosis for Brazilian patients clinically diagnosed with a retinitis pigmentosa pattern of inheritance by using NGS technologies. Sixteen patients with the clinical diagnosis of retinitis pigmentosa were included in the study. Their DNA was sequenced in a panel with 132 genes related to retinal dystrophies using the Illumina(®) platform. Sequence analysis and variation calling was performed using Soft Genetics(®), NextGene, and Geneticist Assistant software. The criteria for pathogenicity analysis were established according to the results of prediction programs (Polyphen 2, Mutation taster and MetaCore™) and comparison of pathogenic variations found with databases. The identified potentially pathogenic variations were all confirmed by Sanger sequencing. There were 89 variations predicted as pathogenic, but only 10 of them supported the conclusion of the

  12. Long-term safety of human retinal progenitor cell transplantation in retinitis pigmentosa patients.

    PubMed

    Liu, Yong; Chen, Shao Jun; Li, Shi Ying; Qu, Ling Hui; Meng, Xiao Hong; Wang, Yi; Xu, Hai Wei; Liang, Zhi Qing; Yin, Zheng Qin

    2017-09-29

    Retinitis pigmentosa is a common genetic disease that causes retinal degeneration and blindness for which there is currently no curable treatment available. Vision preservation was observed in retinitis pigmentosa animal models after retinal stem cell transplantation. However, long-term safety studies and visual assessment have not been thoroughly tested in retinitis pigmentosa patients. In our pre-clinical study, purified human fetal-derived retinal progenitor cells (RPCs) were transplanted into the diseased retina of Royal College of Surgeons (RCS) rats, a model of retinal degeneration. Based on these results, we conducted a phase I clinical trial to establish the safety and tolerability of transplantation of RPCs in eight patients with advanced retinitis pigmentosa. Patients were studied for 24 months. After RPC transplantation in RCS rats, we observed moderate recovery of vision and maintenance of the outer nuclear layer thickness. Most importantly, we did not find tumor formation or immune rejection. In the retinis pigmentosa patients given RPC injections, we also did not observe immunological rejection or tumorigenesis when immunosuppressive agents were not administered. We observed a significant improvement in visual acuity (P < 0.05) in five patients and an increase in retinal sensitivity of pupillary responses in three of the eight patients between 2 and 6 months after the transplant, but this improvement did not appear by 12 months. Our study for the first time confirmed the long-term safety and feasibility of vision repair by stem cell therapy in patients blinded by retinitis pigmentosa. WHO Trial Registration, ChiCTR-TNRC-08000193 . Retrospectively registered on 5 December 2008.

  13. Association of antiretinal antibodies and cystoid macular edema in patients with retinitis pigmentosa.

    PubMed

    Heckenlively, J R; Jordan, B L; Aptsiauri, N

    1999-05-01

    To report the association of antiretinal antibodies in patients with bilateral cystoid macular edema and retinitis pigmentosa. In a prospective study, 30 consecutive patients with bilateral cystoid macular edema and retinitis pigmentosa were tested for antiretinal antibodies. As control subjects, 30 consecutive patients with retinitis pigmentosa who did not have cystoid macular edema and 50 normal subjects without retinitis pigmentosa or cystoid macular edema were tested for antiretinal antibodies. Laboratory personnel performing the antiretinal antibody testing were masked regarding the diagnosis of each patient. Twenty-seven (90%) of 30 patients with retinitis pigmentosa with cystoid macular edema had antiretinal protein antibody activity, compared with three (6%) of 50 normal controls (P < .001) and only four (13%) of 30 control patients with retinitis pigmentosa (P < .001). We found a significant association between cystoid macular edema and the presence of circulating antiretinal antibodies in patients who presented with retinitis pigmentosa and cystoid macular edema. This study suggests that patients with retinitis pigmentosa with cystoid macular edema may have an autoimmune process that is contributing to the formation of cystoid macular edema in retinitis pigmentosa, but to date, there is no direct evidence that the cystoid macular edema is caused by the antiretinal antibodies.

  14. Genetics Home Reference: retinitis pigmentosa

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions retinitis pigmentosa retinitis pigmentosa Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Retinitis pigmentosa is a group of related eye disorders that ...

  15. Visual Acuity is Related to Parafoveal Retinal Thickness in Patients with Retinitis Pigmentosa and Macular Cysts

    PubMed Central

    Brockhurst, Robert J.; Gaudio, Alexander R.; Berson, Eliot L.

    2008-01-01

    Purpose To quantify the prevalence and effect on visual acuity of macular cysts in a large cohort of patients with retinitis pigmentosa. Methods In 316 patients with typical forms of retinitis pigmentosa, we measured visual acuities with Early Treatment Diabetic Retinopathy Study (ETDRS) charts, detected macular cysts with optical coherence tomography (OCT), and quantified retinal thicknesses by OCT. We used the FREQ, LOGISTIC, and GENMOD procedures of SAS to evaluate possible risk factors for cyst prevalence and the MIXED procedure to quantify the relationships of visual acuity to retinal thickness measured at different locations within the macula. Results We found macular cysts in 28% of the patients, 40% of whom had cysts in only one eye. Macular cysts were seen most often in patients with dominant disease and not at all in patients with X-linked disease (p = 0.006). In eyes with macular cysts, multiple regression analysis revealed that visual acuity was inversely and independently related to retinal thickness at the foveal center (p = 0.038) and within a ring spanning an eccentricity of 5° to 10° from the foveal center (p = 0.004). Conclusions Macular cysts are a common occurrence in retinitis pigmentosa, especially among patients with dominantly-inherited disease. Visual acuity is influenced by edema in the parafovea, as well as in the fovea. PMID:18552390

  16. Endothelin-1 Plasma Levels in Patients with both Retinitis Pigmentosa and Flammer Syndrome.

    PubMed

    Todorova, M G; Josifova, T; Konieczka, K

    2015-04-01

    Endothelin-1 is a strong endogenous vasoconstrictor and is also an agent reducing the ocular blood flow. Patients with retinitis pigmentosa are known to have reduced ocular blood flow. This can be secondary to retinal atrophy, but may also partially result from an additional condition, such as a Flammer syndrome. The aim of the study was to investigate whether the endothelin-1 plasma levels in retinitis pigmentosa patients with and without Flammer syndrome are different. In the study we included patients with clinical signs and symptoms of retinitis pigmentosa, confirmed by electrophysiological findings. Blood samples were obtained from 6 retinitis pigmentosa patients with and 4 without Flammer syndrome. The results were related to 30 age- and sex-matched control subjects. Endothelin-1 plasma levels were determined by specific radioimmunoassay. The endothelin-1 plasma levels in retinitis pigmentosa patients with Flammer syndrome were significantly higher than those without Flammer syndrome. The mean (±SD) endothelin-1 levels (pg/mL) in retinitis pigmentosa patients with Flammer syndrome were 4.95 (±1.74), range: (2.37-6.76), whereas in patients without Flammer syndrome they were 1.10 (±0.08), range: 1.00-1.20. Our own normal values are: 1.56 (±0.30), range: (0.90-2.13). All retinitis pigmentosa patients with increased endothelin-1 plasma levels had signs and symptoms related to a Flammer syndrome, such as cold extremities, low blood pressure, reduced feeling of thirst, increased sensitivity in general, e.g., increased sensitivity to certain drugs, increased pain sensitivity and increased sense of smell. Endothelin-1 plasma levels were increased in retinitis pigmentosa patients with but not in patients without Flammer syndrome. Many questions remain open: Why so many retinitis pigmentosa patients suffer from Flammer syndrome, why is the endothelin-1 level in such patients higher than in healthy subjects with Flammer syndrome, how much of the ocular blood flow

  17. Politics and Human Welfare: Retinitis Pigmentosa Patients in South Africa.

    ERIC Educational Resources Information Center

    McKendrick, B. W.; Leketi, M.

    1990-01-01

    The study found that apartheid impacted the sociopsychological and physical circumstances of 12 African and 11 White people with retinitis pigmentosa in South Africa. Findings are discussed in terms of onset of condition, effects on subjects' lives, knowledge of social services, and needs unmet by existing services. (JDD)

  18. Politics and Human Welfare: Retinitis Pigmentosa Patients in South Africa.

    ERIC Educational Resources Information Center

    McKendrick, B. W.; Leketi, M.

    1990-01-01

    The study found that apartheid impacted the sociopsychological and physical circumstances of 12 African and 11 White people with retinitis pigmentosa in South Africa. Findings are discussed in terms of onset of condition, effects on subjects' lives, knowledge of social services, and needs unmet by existing services. (JDD)

  19. Intraretinal hyperreflective foci on spectral-domain optical coherence tomographic images of patients with retinitis pigmentosa.

    PubMed

    Kuroda, Masako; Hirami, Yasuhiko; Hata, Masayuki; Mandai, Michiko; Takahashi, Masayo; Kurimoto, Yasuo

    2014-01-01

    The purpose of this study was to observe the characteristic findings of spectral-domain optical coherence tomography (SD-OCT) images in the retinas of patients with retinitis pigmentosa and to evaluate their distribution patterns in the early and advanced stages of the disease. A total of 184 patients (368 eyes) with retinitis pigmentosa were observed using SD-OCT. We studied the presence or absence of continuous inner/outer segment (IS/OS) lines, presence of thinning of the retinal pigment epithelium-Bruch's membrane complex, and distribution patterns of hyperreflective foci in the inner and outer nuclear layers (INL and ONL). The IS/OS junction had partially disappeared in 275 eyes, which were at the early stage of retinitis pigmentosa (group X), whereas the junction had totally disappeared in 93, which were at the advanced stage of retinitis pigmentosa (group Y). Hyperreflective foci in the INL were observed in a significantly larger proportion of the eyes in group X than in group Y (90% versus 61%, P<0.001), but hyperreflective foci in the ONL were observed in a significantly larger proportion of eyes in group Y than in group X (100% versus 69%, P<0.001). Hyperreflective foci in the INL were more frequently observed in retinas with the early stage of retinitis pigmentosa and hyperreflective foci in the ONL were more frequently observed in the advanced stage. Hyperreflective foci may be indicative of changes in the retinal structure at each stage of retinitis pigmentosa.

  20. Unilateral retinitis pigmentosa.

    PubMed

    Bhattarai, D; Paudel, N; Adhikari, P; Gnyawali, S; Joshi, S N

    2015-01-01

    To report a rare case of unilateral retinitis pigmentosa and to present the clinical features, and findings of multifocal ERG and visual field of this case. A 70-year-old-female diagnosed as Retinitis Pigmentosa in right eye 7 years back, presented with further gradual painless diminution of vision in the very eye and without any similar symptoms in left eye. On examination, the findings (including multifocal ERG and visual field) suggested the features of retinitis pigmentosa in her right eye, while the other eye being unaffected. In this rare case, the distinct features of retinitis pigmentosa are seen only in one eye, and this can be further confirmed from multifocal ERG and visual field. © NEPjOPH.

  1. Uveitis in Patients with Retinitis Pigmentosa: 30 Years' Consecutive Data.

    PubMed

    Dutta Majumder, Parthopratim; Menia, Nitin; Roy, Rupak; Sen, Parveen; George, Amala E; Ganesh, Sudha K; Biswas, Jyotirmay

    2017-09-29

    To describe the clinical pattern of uveitis in patients with retinitis pigmentosa (RP) at a tertiary care eye hospital over a period of 30 years. The medical records of 32 eyes of 22 patients of RP with uveitis were included in this study. Collected data included age, subsets of uveitis, best corrected visual acuities (BCVA), detailed laboratory investigations, and treatment. Mean age at presentation was 53.4 ± 18.8 years, and mean age of diagnosis of RP was 39.2 ± 21.4 years. Uveitis was bilateral in 10 (45.5%) patients. The most common of uveitis in current study was anterior uveitis (56.2%), followed by intermediate uveitis (43.8%). Cataract developed in 12 (37.5%) eyes, and three eyes had raised intraocular pressure. Ten patients (45.5%) required oral steroid, and one patient required oral methotrexate. Uveitis in RP patients is rare, but not uncommon. Coexistence of these disorders might support the inflammatory pathway in etiology of RP.

  2. Spectrum of rhodopsin mutations in Korean patients with retinitis pigmentosa

    PubMed Central

    Kim, Kwang Joong; Kim, Cinoo; Bok, Jeong; Kim, Kyung-Seon; Lee, Eun-Ju; Park, Sung Pyo; Chung, Hum; Han, Bok-Ghee; Kim, Hyung-Lae; Kimm, Kuchan; Yu, Hyeong Gon

    2011-01-01

    Purpose To determine the spectrum and frequency of rhodopsin gene (RHO) mutations in Korean patients with retinitis pigmentosa (RP) and to characterize genotype–phenotype correlations in patients with mutations. Methods The RHO mutations were screened by direct sequencing, and mutation prevalence was measured in patients and controls. The impact of missense mutations to RP was predicted by segregation analysis, peptide sequence alignment, and in silico analysis. The severity of disease in patients with the missense mutations was compared by visual acuity, electroretinography, optical coherence tomography, and kinetic visual field testing. Results Five heterozygous mutations were identified in six of 302 probands with RP, including a novel mutation (c.893C>A, p.A298D) and four known mutations (c.50C>T, p.T17M; c.533A>G, p.Y178C; c.888G>T, p.K296N; and c.1040C>T, p.P347L). The allele frequency of missense mutations was measured in 114 ethnically matched controls. p.A298D, newly identified in a sporadic patient, had never been found in controls and was predicted to be pathogenic. Among the patients with the missense mutations, we observed the most severe phenotype in patients with p.P347L, less severe phenotypes in patients with p.Y178C or p.A298D, and a relatively moderate phenotype in a patient with p.T17M. Conclusions The results reveal the spectrum of RHO mutations in Korean RP patients and clinical features that vary according to mutations. Our findings will be useful for understanding these genetic spectra and the genotype–phenotype correlations and will therefore help with predicting disease prognosis and facilitating the development of gene therapy. PMID:21677794

  3. The cost-effectiveness of the Argus II retinal prosthesis in Retinitis Pigmentosa patients

    PubMed Central

    2014-01-01

    Background Retinitis Pigmentosa (RP) is a hereditary genetic disease causing bilateral retinal degeneration. RP is a leading cause of blindness resulting in incurable visual impairment and drastic reduction in the Quality of life of the patients. Second Sight Medical Products Inc. developed Argus II, a retinal prosthesis system for treating RP. Argus II is the world’s first ever-commercial implant intended to restore some vision in the blind patients. The objective of this study was to assess the cost-effectiveness of the Argus® II Retinal Prosthesis System (Argus II) in Retinitis Pigmentosa (RP) patients. Method A multi -state transition Markov model was developed to determine the cost-effectiveness of Argus II versus usual care in RP from the perspective of healthcare payer. A hypothetical cohort of 1000 RP patients aged 46 years followed up over a (lifetime) 25-year time horizon. Health outcomes were expressed as quality adjusted life years (QALYs) and direct healthcare costs expressed in 2012 €. Results are reported as incremental cost per ratios (ICERs) with outcomes and costs discounted at an annual rate of 3.5%. Results The ICER for Argus II was €14,603/QALY. Taking into account the uncertainty in model inputs the ICER was €14,482/QALY in the probabilistic analysis. In the scenarios of an assumption of no reduction on cost across model visual acuity states or a model time horizon as short as 10 years the ICER increased to €31,890/QALY and €49,769/QALY respectively. Conclusion This economic evaluation shows that Argus II is a cost-effective intervention compared to usual care of the RP patients. The lifetime analysis ICER for Argus II falls below the published societal willingness to pay of EuroZone countries. PMID:24731533

  4. The cost-effectiveness of the Argus II retinal prosthesis in Retinitis Pigmentosa patients.

    PubMed

    Vaidya, Anil; Borgonovi, Elio; Taylor, Rod S; Sahel, José-Alain; Rizzo, Stanislao; Stanga, Paulo Eduardo; Kukreja, Amit; Walter, Peter

    2014-04-14

    Retinitis Pigmentosa (RP) is a hereditary genetic disease causing bilateral retinal degeneration. RP is a leading cause of blindness resulting in incurable visual impairment and drastic reduction in the Quality of life of the patients. Second Sight Medical Products Inc. developed Argus II, a retinal prosthesis system for treating RP. Argus II is the world's first ever-commercial implant intended to restore some vision in the blind patients. The objective of this study was to assess the cost-effectiveness of the Argus® II Retinal Prosthesis System (Argus II) in Retinitis Pigmentosa (RP) patients. A multi -state transition Markov model was developed to determine the cost-effectiveness of Argus II versus usual care in RP from the perspective of healthcare payer. A hypothetical cohort of 1000 RP patients aged 46 years followed up over a (lifetime) 25-year time horizon. Health outcomes were expressed as quality adjusted life years (QALYs) and direct healthcare costs expressed in 2012 €. Results are reported as incremental cost per ratios (ICERs) with outcomes and costs discounted at an annual rate of 3.5%. The ICER for Argus II was €14,603/QALY. Taking into account the uncertainty in model inputs the ICER was €14,482/QALY in the probabilistic analysis. In the scenarios of an assumption of no reduction on cost across model visual acuity states or a model time horizon as short as 10 years the ICER increased to €31,890/QALY and €49,769/QALY respectively. This economic evaluation shows that Argus II is a cost-effective intervention compared to usual care of the RP patients. The lifetime analysis ICER for Argus II falls below the published societal willingness to pay of EuroZone countries.

  5. Psychological Disorders in Patients with Retinitis Pigmentosa in Iran

    PubMed Central

    ADHAMI-MOGHADAM, Farhad; IRAN-POUR, Elham

    2014-01-01

    Abstract Background To identify mental disorders and their prevalence in patients with retinitis pigmentosa (RP). Methods This descriptive study was carried out between January 2009 and January 2010 on 417 patients with RP, who were members of Iran RP Center. The necessary data were collected using questionnaires consisting two parts: The background characteristics and questions assessing the mental health and screening personality and psychosocial disorders, which were designed based on the Minnesota Multiphasic Personality Inventory. Data were analyzed using SPSS software with Chi-square test to assess the relationship between background characteristics and each mental disorder. Scores in the range of 30 and 70 were considered normal. Results Patients with RP suffered from eight mental disorders with the following prevalence: Obsessive compulsive disorder (39.3%), schizophrenia (38.1%), antisocial personality (37.6%), paranoia (36.7%), hypochondrias (35.3%), depression (31.2%), hysteria (26.9%), and hypomania (23.7%). No one had all the eight mental disorders simultaneously. Statistical analysis showed no significant relationship between obsessive compulsive disorder, paranoia, depression, and hysteria and background characteristics. A significant association was found between schizophrenia and onset of RP (P = 0.047). Furthermore, a significant association was seen between hypochondrias and educational level (P = 0.026) as well as income (P = 0.037), and smoking (P = 0.009). There was also a significant association between hypomania and marital status (P = 0.027). Conclusion The findings showed that RP might lead to various mental disorders, especially obsessive compulsive disorder. PMID:26005663

  6. Intraretinal hyperreflective foci on spectral-domain optical coherence tomographic images of patients with retinitis pigmentosa

    PubMed Central

    Kuroda, Masako; Hirami, Yasuhiko; Hata, Masayuki; Mandai, Michiko; Takahashi, Masayo; Kurimoto, Yasuo

    2014-01-01

    Background The purpose of this study was to observe the characteristic findings of spectral-domain optical coherence tomography (SD-OCT) images in the retinas of patients with retinitis pigmentosa and to evaluate their distribution patterns in the early and advanced stages of the disease. Methods A total of 184 patients (368 eyes) with retinitis pigmentosa were observed using SD-OCT. We studied the presence or absence of continuous inner/outer segment (IS/OS) lines, presence of thinning of the retinal pigment epithelium-Bruch’s membrane complex, and distribution patterns of hyperreflective foci in the inner and outer nuclear layers (INL and ONL). Results The IS/OS junction had partially disappeared in 275 eyes, which were at the early stage of retinitis pigmentosa (group X), whereas the junction had totally disappeared in 93, which were at the advanced stage of retinitis pigmentosa (group Y). Hyperreflective foci in the INL were observed in a significantly larger proportion of the eyes in group X than in group Y (90% versus 61%, P<0.001), but hyperreflective foci in the ONL were observed in a significantly larger proportion of eyes in group Y than in group X (100% versus 69%, P<0.001). Conclusion Hyperreflective foci in the INL were more frequently observed in retinas with the early stage of retinitis pigmentosa and hyperreflective foci in the ONL were more frequently observed in the advanced stage. Hyperreflective foci may be indicative of changes in the retinal structure at each stage of retinitis pigmentosa. PMID:24591813

  7. Clinical trial of lutein in patients with retinitis pigmentosa receiving vitamin A treatment

    USDA-ARS?s Scientific Manuscript database

    We sought to determine whether lutein supplementation will slow visual function decline in patients with retinitis pigmentosa receiving vitamin A. DESIGN: Randomized, controlled, double-masked trial of 225 nonsmoking patients, aged 18 to 60 years, evaluated over a 4-year interval. Patients received ...

  8. OPTOMAP WIDEFIELD IMAGING OF THE ARGUS II RETINAL PROSTHESIS IN PATIENTS WITH RETINITIS PIGMENTOSA.

    PubMed

    Israelsen, Paul E; Sadda, SriniVas R; Dorn, Jessy D; Humayun, Mark S; Olmos de Koo, Lisa C

    2016-01-01

    To explore the utility of using ultra-widefield imaging to visualize the Argus II implant in the eyes of three patients with retinitis pigmentosa. Case series of three patients with retinitis pigmentosa who were implanted with the Argus II Retinal Prosthesis System; two of whom were enrolled in the Argus II clinical trial and one received the implant after the commercial release of the device. Optomap widefield fundus autofluorescence and color images of both eyes were taken in all three patients by an experienced technician using the Optos 200Tx imaging system. Analysis focused on fundus autofluorescence images of the implanted eyes and consisted of assessing the location and configuration of the Argus II electrode array and cable, and also the condition of the surrounding retina. Analysis was led by an experienced vitreoretinal surgeon. Optos fundus autofluorescence images of the implanted eyes in all 3 patients gave a wide-angle view of the retina, with the electrode array and cable clearly visible. The status of the array and cable was able to be determined without difficulty. All 3 cases showed an appropriate mild-to-moderate bowing of the cable, and also the electrode array being positioned on or near the macula with a superotemporal tilt. Other features, such as "bone spicules," were also clearly seen. Optos color images were not as useful in the analysis because of an exaggerated green light artifact seen in the implanted versus the nonimplanted eyes. Optomap fundus autofluorescence widefield images are useful in determining the configuration of the Argus II cable and the position of the electrode array on the retina and therefore are a useful component of the postoperative surveillance of patients implanted with the device. Using autofluorescence avoids the generation of a light reflection artifact often seen with Optos color imaging.

  9. Adaptive optics fundus images of cone photoreceptors in the macula of patients with retinitis pigmentosa.

    PubMed

    Tojo, Naoki; Nakamura, Tomoko; Fuchizawa, Chiharu; Oiwake, Toshihiko; Hayashi, Atsushi

    2013-01-01

    The purpose of this study was to examine cone photoreceptors in the macula of patients with retinitis pigmentosa using an adaptive optics fundus camera and to investigate any correlations between cone photoreceptor density and findings on optical coherence tomography and fundus autofluorescence. We examined two patients with typical retinitis pigmentosa who underwent ophthalmological examination, including measurement of visual acuity, and gathering of electroretinographic, optical coherence tomographic, fundus autofluorescent, and adaptive optics fundus images. The cone photoreceptors in the adaptive optics images of the two patients with retinitis pigmentosa and five healthy subjects were analyzed. An abnormal parafoveal ring of high-density fundus autofluorescence was observed in the macula in both patients. The border of the ring corresponded to the border of the external limiting membrane and the inner segment and outer segment line in the optical coherence tomographic images. Cone photoreceptors at the abnormal parafoveal ring were blurred and decreased in the adaptive optics images. The blurred area corresponded to the abnormal parafoveal ring in the fundus autofluorescence images. Cone densities were low at the blurred areas and at the nasal and temporal retina along a line from the fovea compared with those of healthy controls. The results for cone spacing and Voronoi domains in the macula corresponded with those for the cone densities. Cone densities were heavily decreased in the macula, especially at the parafoveal ring on high-density fundus autofluorescence in both patients with retinitis pigmentosa. Adaptive optics images enabled us to observe in vivo changes in the cone photoreceptors of patients with retinitis pigmentosa, which corresponded to changes in the optical coherence tomographic and fundus autofluorescence images.

  10. Structural and functional changes associated with normal and abnormal fundus autofluorescence in patients with retinitis pigmentosa.

    PubMed

    Greenstein, Vivienne C; Duncker, Tobias; Holopigian, Karen; Carr, Ronald E; Greenberg, Jonathan P; Tsang, Stephen H; Hood, Donald C

    2012-02-01

    To analyze the structure and visual function of regions bordering the hyperautofluorescent ring/arcs in retinitis pigmentosa. Twenty-one retinitis pigmentosa patients (21 eyes) with rings/arcs and 21 normal individuals (21 eyes) were studied. Visual sensitivity in the central 10° was measured with microperimetry. Retinal structure was evaluated with spectral-domain optical coherence tomography. The distance from the fovea to disruption/loss of the inner outer segment (IS/OS) junction and thicknesses of the total receptor plus retinal pigment epithelial complex and outer segment plus retinal pigment epithelial complex layers were measured. Results were compared with measurements of the distance from the fovea to the inner and outer borders of the ring/arc seen on fundus autofluorescence. Disruption/loss of the inner outer segment junction occurred closer to the inner border of the ring/arc and it was closer to the fovea in eight eyes. For 19 eyes, outer segment plus and receptor plus RPE complex thicknesses were significantly decreased at locations closer to the fovea than the appearance of the inner border of hyperautofluorescence. Mean visual sensitivity was decreased inside, across, and outside the ring/arc by 3.5 ± 3.8, 8.9 ± 4.8, and 17.0 ± 2.4 dB, respectively. Structural and functional changes can occur inside the hyperfluorescent ring/arc in retinitis pigmentosa.

  11. Post-Cataract Surgery Visual Disturbance in a Retinitis Pigmentosa Patient with Asteroid Hyalosis

    PubMed Central

    Jingami, Yoko; Otani, Atsushi; Kojima, Hiroshi; Makiyama, Yukiko; Yoshimura, Nagahisa

    2011-01-01

    A patient with retinitis pigmentosa showed visual disturbances following successful cataract surgery. He had a dense asteroid hyalosis in the eye before cataract surgery. After the surgery he noticed that his vision became worse. The visual disturbance was explained as being caused by the progression of retinal degeneration. Although the electroretinogram was non-recordable, the degeneration of macular area appeared relatively small. We considered that dense asteroid hyalosis was responsible for his visual disturbances, and pars plana vitrectomy (PPV) was performed to remove the asteroid hyalosis. After the PPV, rapid improvement of his visual acuity was observed. Cataract surgery may affect the status of asteroid hyalosis and cause rapid visual loss. PPV should be considered for retinitis pigmentosa patients with dense asteroid hyalosis, especially when a large decrease in visual acuity is noted shortly after cataract surgery. PMID:21941506

  12. Post-cataract surgery visual disturbance in a retinitis pigmentosa patient with asteroid hyalosis.

    PubMed

    Jingami, Yoko; Otani, Atsushi; Kojima, Hiroshi; Makiyama, Yukiko; Yoshimura, Nagahisa

    2011-05-01

    A patient with retinitis pigmentosa showed visual disturbances following successful cataract surgery. He had a dense asteroid hyalosis in the eye before cataract surgery. After the surgery he noticed that his vision became worse. The visual disturbance was explained as being caused by the progression of retinal degeneration. Although the electroretinogram was non-recordable, the degeneration of macular area appeared relatively small. We considered that dense asteroid hyalosis was responsible for his visual disturbances, and pars plana vitrectomy (PPV) was performed to remove the asteroid hyalosis. After the PPV, rapid improvement of his visual acuity was observed. Cataract surgery may affect the status of asteroid hyalosis and cause rapid visual loss. PPV should be considered for retinitis pigmentosa patients with dense asteroid hyalosis, especially when a large decrease in visual acuity is noted shortly after cataract surgery.

  13. Retinitis pigmentosa in southern Africa.

    PubMed

    Greenberg, J; Bartmann, L; Ramesar, R; Beighton, P

    1993-11-01

    Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders which are a common cause of genetic blindness. The relative frequencies of the different forms of RP in South Africa, as determined from the register at the DNA banking centre for RP at the Department of Human Genetics, University of Cape Town, are presented and discussed. Of the 125 families analysed, 29 (23%) showed autosomal dominant, 33 (27%) autosomal recessive and 3 (3%) X-linked inheritance. In 10 families the pedigree data were insufficient to allow accurate genetic subtyping and a further 50 patients were sporadic without a family history of RP or other syndromic features which would allow categorization.

  14. Associations Between Outer Retinal Structures and Focal Macular Electroretinograms in Patients With Retinitis Pigmentosa.

    PubMed

    Kominami, Taro; Ueno, Shinji; Kominami, Azusa; Nakanishi, Ayami; Yasuda, Shunsuke; Piao, Chang-Hua; Okado, Satoshi; Terasaki, Hiroko

    2017-10-01

    Our earlier study showed that the width of the intact ellipsoid zone (EZ) of the photoreceptors was significantly but weakly correlated with the amplitudes of the focal macular ERGs (FMERGs). The aim of this study was to determine a microstructure of the photoreceptors in the spectral-domain optical coherence tomographic (SD-OCT) images that was more strongly correlated with the FMERG parameters in eyes with retinitis pigmentosa (RP). This was a retrospective, observational study. The medical records of 65 patients with RP were reviewed. FMERGs were elicited by a 15-degree stimulus spot. The width of the EZ and the outer segment (OS) area surrounded by EZ and retinal pigment epithelium in the SD-OCT images within 15 degrees of the fovea were evaluated. Spearman correlation tests and multiple stepwise regression analyses were performed. There was a strong correlation between the amplitudes of FMERGs and the EZ width (r = 0.68 for a-wave amplitude; r = 0.64 for b-wave amplitude), and also between the amplitudes of the FMERGs and the OS area (r = 0.69 for a-wave amplitude; r = 0.67 for b-wave amplitude). However, some patients had long EZ widths but had severely reduced FMERGs. Multiple stepwise regression analyses showed that the OS area was the only significant independent predictor of the amplitudes of FMERGs (P < 0.001). The OS area might be a better morphological structure to use to predict the physiological function of the macula.

  15. Altered Antioxidant-Oxidant Status in the Aqueous Humor and Peripheral Blood of Patients with Retinitis Pigmentosa

    PubMed Central

    Martínez-Fernández de la Cámara, Cristina; Salom, David; Sequedo, Ma Dolores; Hervás, David; Marín-Lambíes, Cristina; Aller, Elena; Jaijo, Teresa; Díaz-LLopis, Manuel; Millán, José María; Rodrigo, Regina

    2013-01-01

    Retinitis Pigmentosa is a common form of hereditary retinal degeneration constituting the largest Mendelian genetic cause of blindness in the developed world. It has been widely suggested that oxidative stress possibly contributes to its pathogenesis. We measured the levels of total antioxidant capacity, free nitrotyrosine, thiobarbituric acid reactive substances (TBARS) formation, extracellular superoxide dismutase (SOD3) activity, protein, metabolites of the nitric oxide/cyclic GMP pathway, heme oxygenase-I and inducible nitric oxide synthase expression in aqueous humor or/and peripheral blood from fifty-six patients with retinitis pigmentosa and sixty subjects without systemic or ocular oxidative stress-related disease. Multivariate analysis of covariance revealed that retinitis pigmentosa alters ocular antioxidant defence machinery and the redox status in blood. Patients with retinitis pigmentosa present low total antioxidant capacity including reduced SOD3 activity and protein concentration in aqueous humor. Patients also show reduced SOD3 activity, increased TBARS formation and upregulation of the nitric oxide/cyclic GMP pathway in peripheral blood. Together these findings confirmed the hypothesis that patients with retinitis pigmentosa present reduced ocular antioxidant status. Moreover, these patients show changes in some oxidative-nitrosative markers in the peripheral blood. Further studies are needed to clarify the relationship between these peripheral markers and retinitis pigmentosa. PMID:24069283

  16. Altered antioxidant-oxidant status in the aqueous humor and peripheral blood of patients with retinitis pigmentosa.

    PubMed

    Martínez-Fernández de la Cámara, Cristina; Salom, David; Sequedo, Ma Dolores; Hervás, David; Marín-Lambíes, Cristina; Aller, Elena; Jaijo, Teresa; Díaz-Llopis, Manuel; Millán, José María; Rodrigo, Regina

    2013-01-01

    Retinitis Pigmentosa is a common form of hereditary retinal degeneration constituting the largest Mendelian genetic cause of blindness in the developed world. It has been widely suggested that oxidative stress possibly contributes to its pathogenesis. We measured the levels of total antioxidant capacity, free nitrotyrosine, thiobarbituric acid reactive substances (TBARS) formation, extracellular superoxide dismutase (SOD3) activity, protein, metabolites of the nitric oxide/cyclic GMP pathway, heme oxygenase-I and inducible nitric oxide synthase expression in aqueous humor or/and peripheral blood from fifty-six patients with retinitis pigmentosa and sixty subjects without systemic or ocular oxidative stress-related disease. Multivariate analysis of covariance revealed that retinitis pigmentosa alters ocular antioxidant defence machinery and the redox status in blood. Patients with retinitis pigmentosa present low total antioxidant capacity including reduced SOD3 activity and protein concentration in aqueous humor. Patients also show reduced SOD3 activity, increased TBARS formation and upregulation of the nitric oxide/cyclic GMP pathway in peripheral blood. Together these findings confirmed the hypothesis that patients with retinitis pigmentosa present reduced ocular antioxidant status. Moreover, these patients show changes in some oxidative-nitrosative markers in the peripheral blood. Further studies are needed to clarify the relationship between these peripheral markers and retinitis pigmentosa.

  17. Heading perception in patients with advanced retinitis pigmentosa

    NASA Technical Reports Server (NTRS)

    Li, Li; Peli, Eli; Warren, William H.

    2002-01-01

    PURPOSE: We investigated whether retinis pigmentosa (RP) patients with residual visual field of < 100 degrees could perceive heading from optic flow. METHODS: Four RP patients and four age-matched normally sighted control subjects viewed displays simulating an observer walking over a ground. In experiment 1, subjects viewed either the entire display with free fixation (full-field condition) or through an aperture with a fixation point at the center (aperture condition). In experiment 2, patients viewed displays of different durations. RESULTS: RP patients' performance was comparable to that of the age-matched control subjects: heading judgment was better in the full-field condition than in the aperture condition. Increasing display duration from 0.5 s to 1 s improved patients' heading performance, but giving them more time (3 s) to gather more visual information did not consistently further improve their performance. CONCLUSIONS: RP patients use active scanning eye movements to compensate for their visual field loss in heading perception; they might be able to gather sufficient optic flow information for heading perception in about 1 s.

  18. Heading perception in patients with advanced retinitis pigmentosa

    NASA Technical Reports Server (NTRS)

    Li, Li; Peli, Eli; Warren, William H.

    2002-01-01

    PURPOSE: We investigated whether retinis pigmentosa (RP) patients with residual visual field of < 100 degrees could perceive heading from optic flow. METHODS: Four RP patients and four age-matched normally sighted control subjects viewed displays simulating an observer walking over a ground. In experiment 1, subjects viewed either the entire display with free fixation (full-field condition) or through an aperture with a fixation point at the center (aperture condition). In experiment 2, patients viewed displays of different durations. RESULTS: RP patients' performance was comparable to that of the age-matched control subjects: heading judgment was better in the full-field condition than in the aperture condition. Increasing display duration from 0.5 s to 1 s improved patients' heading performance, but giving them more time (3 s) to gather more visual information did not consistently further improve their performance. CONCLUSIONS: RP patients use active scanning eye movements to compensate for their visual field loss in heading perception; they might be able to gather sufficient optic flow information for heading perception in about 1 s.

  19. Assessment of central retinal function in patients with advanced retinitis pigmentosa.

    PubMed

    Gerth, Christina; Wright, Tom; Héon, Elise; Westall, Carol A

    2007-03-01

    To assess central retinal function in patients with advanced retinitis pigmentosa (RP) using the multifocal (mf)ERG and static perimetry. Patients with RP; a nonrecordable, full-field (ff)ERG; and visual acuity (VA) of patients underwent mfERG testing (103 hexagons, and 2.67 and 5.33 cd . s . m(-2) flash intensities) and static perimetry (103 corresponding areas) in the better eye. First-order kernel mfERGs were analyzed for total noise, signal-to-noise ratio, response amplitude, and implicit time. The number of areas with recordable mfERG responses were counted and compared with visual field (VF) sensitivity. Twenty-nine patients aged 16 to 68 years with a VA of 0.02 to 1.0 logMAR and a kinetic VF of 10 degrees to 60 degrees in diameter were included. mfERGs were successfully performed in 22 of 29 patients. Responses were detected in at least one stimulated area in 22 of 22 patients, with an overall response detection of 9.8% in all stimulated areas and no difference between flash intensities. All responses were diminished severely in response density P1-N1, with normal P1 implicit time in 50% of the recordings. No predictive factors for recordable mfERG responses were identified. VF results were recorded reliably in 27 of 29 patients, with a 40% response detection rate. mfERG responses were recordable in at least one area in all successfully tested patients with advanced RP. Response detection and performance was significantly higher for static perimetry. Static perimetry may be a more sensitive primary outcome measure of central vision function than the mfERG in patients with advanced RP and nonrecordable ffERGs.

  20. Chlorogenic acid supplementation improves multifocal electroretinography in patients with retinitis pigmentosa.

    PubMed

    Shin, Joo Young; Yu, Hyeong Gon

    2014-01-01

    To evaluate the effect of chlorogenic acid supplementation in patients with retinitis pigmentosa, we evaluated objective change in visual function with multifocal electroretinography, along with visual acuity, visual field, standard electroretinography, and contrast sensitivity. Eighteen patients diagnosed with retinitis pigmentosa were enrolled in this prospective, non-comparative, single-arm study. Multifocal electroretinography, best-corrected visual acuity in Early Treatment Diabetic Retinopathy Study letters, total point score on visual field examination with Humphrey Field Analyzer II, electroretinography, and contrast sensitivity were measured and repeated after 3 months supplementation with chlorogenic acid. The amplitude of ring 5 was significantly higher on multifocal electroretinography after 3 months of chlorogenic acid supplementation (7.2 ± 9.5 vs 8.3 ± 10.8 nV/deg(2), mean ± standard deviation, P = 0.022). There were no significant changes in the best-corrected visual acuity, total point score on Humphrey Field Analyzer, 30 Hz flicker amplitude on standard electroretinography, or contrast sensitivity. Chlorogenic acid may have a beneficial effect on the peripheral area at the margins of retinal degeneration, and should be considered as an anti-oxidant for the management of retinitis pigmentosa.

  1. Retinitis pigmentosa in Puerto Rico.

    PubMed

    Tous, Horacio M; Izquierdo, Natalio J

    2006-12-01

    Previous studies have reported that the prevalence of retinitis pigmentosa (RP) varies between one per 3,000 to one in per 5,000 in the general population. To study the incidence and ocular findings of RP in a sub-urban community in Puerto Rico. We conducted a non-concurrent prospective study of 10,100 patients in a sub-urban San Juan community. 44 out of the 10,100 patients had RP (0.44%). Eight out of the 44 patients (18%) had nystagmus, twenty-eight (31.8%) had microcornea, 3 patients (6.8%) had sluggish papillary reaction. Six patients (13.6%) had mild cataracts, 27 (65.9%)had attenuated retinal vessels and thirty five patients (81.4%) had bony spicules. Fifteen patients (34.1%) out of the 44 had retinitis pigmentosa as part of the Bardet-Biedl syndrome. Incidence of RP in Puerto Rico is higher when compared to Maine and Spain (p < 0.001). Autosomal recessive pattern of inheritance is the most common in Puerto Rico. These findings could be due to the island's geographic isolation, and inbreeding.

  2. A modified protocol for the assessment of visual function in patients with retinitis pigmentosa.

    PubMed

    Lodha, N; Westall, C A; Brent, M; Abdolell, M; Héon, E

    2003-01-01

    The assessment of visual function for retinitis pigmentosa routinely includes: electroretinography, visual acuity and visual field-testing. Patients with retinitis pigmentosa sometimes complain of changes in visual function, which are not paralleled by routine eye tests. To determine which visual function test or group of tests can predict reliably perceived visual function in patients with retinitis pigmentosa Subjects with progressive retinitis pigmentosa are recruited from the Ocular genetics program of The Hospital for Sick Children and Mount Sinai Hospital, Toronto. Subjects will be tested four times over the over the period of one year. On each visit they undergo following tests- 1) Central visual acuity (VA) using the crowded logMAR acuity chart, 2) Contrast Sensitivity (CS) using Pelli-Robson contrast sensitivity chart, 3) Visual field test (VF) using Humphrey (10-2), 4) Color vision using Mollon-Reffin 'minimalist' test and 5) Subjective visual function questionnaire testing near and global perceived visual function respectively. Phase I (baseline and visit I measure) results are reported. Total of sixty-eight patients with mean age of 41 years, age range of twelve to sixty seven were tested. Of these thirty-one were males and thirty-seven were females. Repeat testing correlation was high (r>0.8, p<0.05) for all parameters between baseline visit and visit I. The near perceived visual function correlated best with the combination of visual acuity and contrast sensitivity. The global perceived visual function correlated best with combination of visual field and visual acuity. Objective measure of central visual function (HVF 10-2) correlated best with contrast sensitivity. The addition of contrast sensitivity and Humphrey visual field to routine visual assessment should improve the quality of the longitudinal data of visual function recorded on these patients. Patients will be re- tested at six months and one-year interval. To date of the sixty

  3. A pilot study of an acupuncture protocol to improve visual function in retinitis pigmentosa patients

    PubMed Central

    Bittner, Ava K; Gould, Jeffrey M; Rosenfarb, Andy; Rozanski, Collin; Dagnelie, Gislin

    2014-01-01

    Background Patients with retinitis pigmentosa are motivated to try complementary or integrative therapies to slow disease progression. Basic science, clinical research and retinitis pigmentosa patients' self-reports support the hypothesis that acupuncture may improve visual function. Methods A prospective, case series, pilot study enrolled 12 adult patients with RP treated at an academic medical centre with a standardised protocol that combined electroacupuncture to the forehead and below the eyes and acupuncture to the body, at 10 half-hour sessions over two weeks. Pre- and post-treatment tests included Early Treatment Diabetic Retinopathy Study visual acuity (VA), Pelli-Robson contrast sensitivity (CS), Goldmann visual fields, and dark-adapted full-field stimulus threshold (FST)(n = 9). Scotopic Sensitivity Tester-1 (SST-1) dark-adaptometry was performed on the last two subjects. Results Six of 12 subjects had measurable, significant visual function improvements after treatment. Three of nine subjects tested with the FST had a significant 10.3 to 17.5 dB (that is, 13- to 53-fold) improvement in both eyes at one week after acupuncture, maintained for at least 10 to 12 months, which was well outside typical test-retest variability (95% CI: 3–3.5 dB) previously found in retinitis pigmentosa. SST-1 dark-adaptation was shortened in both subjects tested on average by 48.5 per cent at one week (range 36 to 62 per cent across 10 to 30 dB), which was outside typical coefficients of variation of less than 30 per cent previously determined in patients with retinitis pigmentosa and normals. Four of the five subjects with psychophysically measured scotopic sensitivity improvements reported subjective improvements in vision at night or in dark environments. One subject had 0.2 logMAR improvement in VA; another had 0.55 logCS improvement. Another subject developed more than 20 per cent improvement in the area of the Goldmann visual fields. The acupuncture protocol was

  4. A pilot study of an acupuncture protocol to improve visual function in retinitis pigmentosa patients.

    PubMed

    Bittner, Ava K; Gould, Jeffrey M; Rosenfarb, Andy; Rozanski, Collin; Dagnelie, Gislin

    2014-05-01

    Patients with retinitis pigmentosa are motivated to try complementary or integrative therapies to slow disease progression. Basic science, clinical research and retinitis pigmentosa patients' self-reports support the hypothesis that acupuncture may improve visual function. A prospective, case series, pilot study enrolled 12 adult patients with RP treated at an academic medical centre with a standardised protocol that combined electroacupuncture to the forehead and below the eyes and acupuncture to the body, at 10 half-hour sessions over two weeks. Pre- and post-treatment tests included Early Treatment Diabetic Retinopathy Study visual acuity (VA), Pelli-Robson contrast sensitivity (CS), Goldmann visual fields, and dark-adapted full-field stimulus threshold (FST)(n = 9). Scotopic Sensitivity Tester-1 (SST-1) dark-adaptometry was performed on the last two subjects. Six of 12 subjects had measurable, significant visual function improvements after treatment. Three of nine subjects tested with the FST had a significant 10.3 to 17.5 dB (that is, 13- to 53-fold) improvement in both eyes at one week after acupuncture, maintained for at least 10 to 12 months, which was well outside typical test-retest variability (95% CI: 3-3.5 dB) previously found in retinitis pigmentosa. SST-1 dark-adaptation was shortened in both subjects tested on average by 48.5 per cent at one week (range 36 to 62 per cent across 10 to 30 dB), which was outside typical coefficients of variation of less than 30 per cent previously determined in patients with retinitis pigmentosa and normals. Four of the five subjects with psychophysically measured scotopic sensitivity improvements reported subjective improvements in vision at night or in dark environments. One subject had 0.2 logMAR improvement in VA; another had 0.55 logCS improvement. Another subject developed more than 20 per cent improvement in the area of the Goldmann visual fields. The acupuncture protocol was completed and well tolerated

  5. Screening for mutations in rhodopsin and peripherin/RDS in patients with autosomal dominant retinitis pigmentosa

    SciTech Connect

    Rodriguez, J.A.; Gannon, A.M.; Daiger, S.P.

    1994-09-01

    Mutations in rhodopsin account for approximately 30% of all cases of autosomal dominant retinits pigmentosa (adRP) and mutations in peripherin/RDS account for an additional 5% of cases. Also, mutations in rhodopsin can cause autosomal recessive retinitis pigmentosa and mutations in peripherin/RDS can cause dominant macular degeneration. Most disease-causing mutations in rhodopsin and peripherin/RDS are unique to one family or, at most, to a few families within a limited geographic region, though a few mutations are found in multiple, unrelated families. To further determine the spectrum of genetic variation in these genes, we screened DNA samples from 134 unrelated patients with retinitis pigmentosa for mutations in both rhodopsin and peripherin/RDS using SSCP followed by genomic sequencing. Of the 134 patients, 86 were from families with apparent adRP and 48 were either isolated cases or were from families with an equivocal mode of inheritance. Among these patients we found 14 distinct rhodopsin mutations which are likely to cause retinal disease. Eleven of these mutations were found in one individual or one family only, whereas the Pro23His mutation was found in 14 {open_quotes}unrelated{close_quotes}individuals. The splice-site mutation produces dominant disease though with highly variable expression. Among the remaining patients were found 6 distinct peripherin/RDS mutations which are likely to cause retinal disease. These mutations were also found in one patient or family only, except the Gly266Asp mutation which was found in two unrelated patients. These results confirm the expected frequency and broad spectrum of mutations causing adRP.

  6. Phenotypic conservation in patients with X-linked retinitis pigmentosa caused by RPGR mutations.

    PubMed

    Zahid, Sarwar; Khan, Naheed; Branham, Kari; Othman, Mohammad; Karoukis, Athanasios J; Sharma, Nisha; Moncrief, Ashley; Mahmood, Mahdi N; Sieving, Paul A; Swaroop, Anand; Heckenlively, John R; Jayasundera, Thiran

    2013-08-01

    For patients with X-linked retinitis pigmentosa and clinicians alike, phenotypic variability can be challenging because it complicates counseling regarding patients' likely visual prognosis. To evaluate the clinical findings from patients with X-linked retinitis pigmentosa with 13 distinct RPGR mutations and assess for phenotypic concordance or variability. Retrospective medical record review of data collected from 1985 to 2011. Kellogg Eye Center, University of Michigan. A total of 42 patients with X-linked retinitis pigmentosa with mutations in RPGR. Age at first visit ranged from 4 to 53 years, with follow-up ranging from 1 to 11 visits (median follow-up time, 5.5 years; range, 1.4-32.7 years, for 23 patients with >1 visit). Clinical data assessed for concordance included visual acuity (VA), Goldmann visual fields (GVFs), and full-field electroretinography (ERG). Electroretinography phenotype (cone-rod vs rod-cone dysfunction) was defined by the extent of photopic vs scotopic abnormality. Qualitative GVF phenotype was determined by the GVF pattern, where central or peripheral loss suggested cone or rod dysfunction, respectively. Goldmann visual fields were also quantified and compared among patients. Each mutation was detected in 2 or more related or unrelated patients. Five mutations in 11 patients displayed strong concordance of VA, while 4 mutations in 16 patients revealed moderate concordance of VA. A definitive cone-rod or rod-cone ERG pattern consistent among patients was found in 6 of 13 mutations (46.2%); the remaining mutations were characterized by patients demonstrating both phenotypes or who had limited data or nonrecordable ERG values. Concordant GVF phenotypes (7 rod-cone pattern vs 4 cone-rod pattern) were seen in 11 of 13 mutations (84.6%). All 6 mutations displaying a constant ERG pattern within the mutation group revealed a GVF phenotype consistent with the ERG findings. While VA and ERG phenotypes are concordant in only some patients carrying

  7. Quantifying Fundus Autofluorescence in Patients With Retinitis Pigmentosa

    PubMed Central

    Schuerch, Kaspar; Woods, Russell L.; Lee, Winston; Duncker, Tobias; Delori, François C.; Allikmets, Rando; Tsang, Stephen H.; Sparrow, Janet R.

    2017-01-01

    Purpose Using quantitative fundus autofluorescence (qAF), we analyzed short-wavelength autofluorescent (SW-AF) rings in RP. Methods Short-wavelength autofluorescent images (486 nm excitation) of 40 patients with RP (69 eyes) were acquired with a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference. Mean qAF was measured in eight preset segments (qAF8) and in region of interest (ROI)-qAF (200–700 μm) within and external to the borders of the rings at superior, temporal, and inferior sites relative to the ring. For both groups, qAF in patients with RP was compared to age-similar and race/ethnicity-matched healthy eyes at equivalent retinal locations. Results In 71% of eyes of RP patients, qAF8 acquired internal to the inner border of the ring, was within the 95% confidence interval (CI) for healthy eyes, while in the remaining RP eyes qAF8 was either higher or lower than the CI. Measured external to the ring, qAF8 values were within the CI in 47% of RP eyes with the other eyes being higher or lower. In 28% of sites measured by ROI-qAF within the SW-AF ring, values were above the 95% CI of healthy controls. Region of interest-qAF measured just external to the ring was within the CI of healthy eyes in 74% of locations. The average local elevation in qAF within the ring was approximately 15%. In SD-OCT scans, photoreceptor-attributable reflectivity bands were thinned within and external to the ring. Conclusions Increased fluorophore production may be a factor in the formation of the SW-AF rings in RP. PMID:28358950

  8. Retinal vessel oxygen saturation and vessel diameter in retinitis pigmentosa.

    PubMed

    Eysteinsson, Thor; Hardarson, Sveinn H; Bragason, David; Stefánsson, Einar

    2014-08-01

    To assess retinal vessel oxygen saturation and retinal vessel diameter in retinitis pigmentosa. A retinal oximeter (Oxymap ehf., Reykjavik, Iceland) was used to measure retinal vessel oxygen saturation and vessel diameter in ten patients with retinitis pigmentosa (RP) (mean age 49 years, range 23-71 years). Results were compared with age- and gender-matched healthy individuals. All patients had advanced stage of the disease with visual fields restricted to the macular region. Oxygen saturation in retinal venules was 58.0 ± 6.2% in patients with RP and 53.4 ± 4.8% in healthy subjects (p = 0.017). Oxygen saturation in retinal arterioles was not significantly different between groups (p = 0.65). The mean diameter of retinal arterioles was 8.9 ± 1.6 pixels in patients with RP and 11.4 ± 1.2 in healthy controls (p < 0.0001). The corresponding diameters for venules were 10.1 ± 1.2 (RP) and 15.3 ± 1.7 (healthy, p < 0.0001). Increased venous saturation and decreased retinal vessel diameter suggest decreased oxygen delivery from the retinal circulation in retinitis pigmentosa. This is probably secondary to tissue atrophy and reduced oxygen consumption. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  9. [Analysis of clinical phenotype and mode of inheritance in retinitis pigmentosa patients with consanguineous marriage].

    PubMed

    Rong, Wei-ning; Sheng, Xun-lun; Liu, Ya-ni

    2012-10-01

    To analyse the mode of inheritance and clinical characteristics of retinitis pigmentosa (RP) patients with consanguineous marriage. RP patients were recruited for this study in Ningxia Eye Hospital from September 2009 to July 2011. All patients received complete ophthalmic examination. The mode of inheritance were determined based on family history and marriage history. Clinical features were characterized by complete ophthalmic examinations including visual acuity, macular OCT, visual field and electroretinogram (ERG). A total of 143 individuals with RP (33 families) were recruited. Based on analysis of family history and marriage history, 20 RP families (23 patients) had consanguineous marriage history accounted for 60.6% RP families (16.1% RP patients). There were 4 patients (from 4 families) diagnosed as Usher syndrome. In 20 RP families with consanguineous marriage history, 7 families (35.0%) were Hui ethnicity and 13 families (65%) were Han ethnicity. The marriages of 15 families were between first cousins and 3 families were between second cousins, only 2 families were between half cousins matrimony. Of 23 RP patients, 12 were males and 11 were females. The average age of onset was 11.4 ± 6.8 years and the average age of recruitment was (32.0 ± 13.5) years. The best-corrected visual acuity was less than 0.6 in 78.2% patients. According to the features of the fundus, 13 patients were classical retinitis pigmentosa and 10 patients were retinitis pigmentosa sine pigmento. Visual field examination showed that all patients had varying degrees of peripheral visual field defect. Retinal neuroepithelial layer of macular and peripheral retina became thinner and retinal photoreceptors were disappeared. The average thickness of macular fovea was (186.1 ± 78.7) µm on right eyes and (187.4 ± 76.3) µm on left eyes. The incidence of RP with consanguineous marriages was high in Ningxia Region. The mode of inheritance of RP patients with consanguinity is autosomal

  10. Contrast sensitivity evaluation with filter contact lenses in patients with retinitis pigmentosa: a pilot study

    PubMed Central

    Carracedo, Gonzalo; Carballo, Jesús; Loma, Elena; Felipe, Gema; Cacho, Isabel

    2012-01-01

    Purpose The aim of this pilot study was to test whether retinitis pigmentosa patients would benefit from filter contact lenses as an effective optical aid against glare and photophobia. Methods Fifteen subjects with retinitis pigmentosa were enrolled in this study. All of them were evaluated with filter soft contact lenses (MaxSight), filter glasses (CPF 527) and without filters (control). All patients were assessed for the three aid conditions by means of best corrected visual acuity (BCVA), contrast sensitivity (without glare and with central and peripheral glare)(CSV-1000) and a specific subjective questionnaire about quality of vision. Results BCVA was slightly better with filters than without filter but the differences were not statistically significant. Contrast sensitivity without glare improved significantly with the contact lenses (p < 0.05). The central glare had significant differences for the frequencies of 3 cpd and 18 cpd between the contact lens filter and the control group (p = 0.021 and p = 0.044, respectively). For the peripheral glare contrast sensitivity improved with contact lens versus control group for highest frequencies, 12 and 18 cpd (p < 0.001 and p = 0.045, respectively). According to the questionnaire the contact lens filter gave them more visual comfort than the glasses filter under the scenarios of indoors glare, outdoors activities and indoors comfort. Conclusion The filter contact lenses seem to be a good option to improve the quality of vision of patients with retinitis pigmentosa.

  11. Structure-function correlations in Retinitis Pigmentosa patients with partially preserved vision: a voxel-based morphometry study.

    PubMed

    Rita Machado, Ana; Carvalho Pereira, Andreia; Ferreira, Fábio; Ferreira, Sónia; Quendera, Bruno; Silva, Eduardo; Castelo-Branco, Miguel

    2017-09-12

    Retinitis Pigmentosa is a group of hereditary retinal dystrophy disorders associated with progressive peripheral visual field loss. The impact of this retinal loss in cortical gray matter volume has not been addressed before in Retinitis Pigmentosa patients with low vision. Voxel-based morphometry was applied to study whole brain gray matter volume changes in 27 Retinitis Pigmentosa patients with partially preserved vision and 38 age- and gender-matched normally sighted controls to determine whether peripheral visual loss can lead to changes in gray matter volume. We found significant reductions in gray matter volume that were restricted to the occipital cortex of patients. The anteromedial pattern of reduced gray matter volume in visual primary and association cortices was significantly correlated with the extent of the peripheral visual field deficit in this cohort. Moreover, this pattern was found to be associated with the extent of visual field loss. In summary, we found specific visual cortical gray matter loss in Retinitis Pigmentosa patients associated with their visual function profile. The spatial pattern of gray matter loss is consistent with disuse-driven neuronal atrophy which may have clinical implications for disease management, including prosthetic restoration strategies.

  12. Clinical Trial of Lutein in Patients with Retinitis Pigmentosa Receiving Vitamin A

    PubMed Central

    Berson, Eliot L.; Rosner, Bernard; Sandberg, Michael A.; Weigel-DiFranco, Carol; Brockhurst, Robert J.; Hayes, K.C.; Johnson, Elizabeth J.; Anderson, Ellen J.; Johnson, Chris A.; Gaudio, Alexander R.; Willett, Walter C.; Schaefer, Ernst J.

    2010-01-01

    Objective To determine whether lutein supplementation will slow visual function decline in patients with retinitis pigmentosa receiving vitamin A. Design Randomized, controlled, double-masked trial of 225 non-smoking patients, age 18-60 years, evaluated over a 4-year interval. Patients received lutein 12 mg or a control tablet daily. All were given vitamin A palmitate 15,000 IU/day. Randomization took into account genetic type and baseline serum lutein. Main Outcome Measures The primary outcome was the total point score for the Humphrey Field Analyzer (HFA) 30-2 program; pre-specified secondary outcomes were the total point scores for the 60-4 program and for the 30-2 and 60-4 combined, 30-Hz electroretinogram amplitude, and ETDRS acuity. Results No significant difference in rate of decline was found between the lutein + A and control + A groups over a 4-year interval for the HFA 30-2 program. For the HFA 60-4 program a decrease in mean rate of sensitivity loss was observed in the lutein + A group (p=0.05). Mean decline with the 60-4 program was slower among those with the highest serum lutein or with the highest increase in macular pigment optical density (MPOD) at follow-up (p= 0.01 and p=0.006 respectively). Those with the highest increase in MPOD also had the slowest decline in 30-2 and 60-4 combined field sensitivity (p=0.005). No significant toxic side effects of lutein supplementation were observed. Conclusion Lutein supplementation 12 mg/d slowed loss of midperipheral visual field on average among nonsmoking adults with retinitis pigmentosa taking vitamin A. Application to Clinical Practice Data are presented that support use of lutein 12 mg/day to slow visual field loss among non-smoking adults with retinitis pigmentosa on vitamin A. Trial Registry Randomized Clinical Trial for Retinitis Pigmentosa, NCT00346333, www.ClinicalTrial.gov PMID:20385935

  13. A patient homozygous for the SCA6 gene with retinitis pigmentosa.

    PubMed

    Fukutake, T; Kamitsukasa, I; Arai, K; Hattori, T; Nakajima, T

    2002-05-01

    The present authors studied a 55-year-old-patient homozygous for the SCA6 gene who experienced frequent attacks of positional vertigo at 37 years of age with subsequent staggering gait and night blindness. Retinitis pigmentosa (RP), as well as cerebellar ataxia and vertical antidirectional nystagmus, were detected. The subject's parents were first cousins, and two of his three male cousins, whose parents were also first cousins, had RP without ataxia or nystagmus. The numbers of CAG repeats in the expanded alleles of the SCA6 gene found by molecular analysis were 21 and 21. The genetic results were negative for SCA1, SCA2, SCA3, SCA7 and dentatorubral pallidoluysian atrophy. The retinal degeneration in this patient is most likely to be secondary to a genetic disorder of autosomal or X-linked recessive inheritance rather than SCA6. Other reported cases of patients homozygous for the SCA6 gene are also reviewed.

  14. Mutation spectrum of the rhodopsin gene among patients with autosomal dominant retinitis pigmentosa

    SciTech Connect

    Dryja, T.P.; Han, L.B.; Cowley, G.S.; McGee, T.L.; Berson, E.L. )

    1991-10-15

    The authors searched for point mutations in every exon of the rhodopsin gene in 150 patients from separate families with autosomal dominant retinitis pigmentosa. Including the 4 mutations the authors reported previously, they found a total of 17 different mutations that correlate with the disease. Each of these mutations is a single-base substitution corresponding to a single amino acid substitution. Based on current models for the structure of rhodopsin, 3 of the 17 mutant amino acids are normally located on the cytoplasmic side of the protein, 6 in transmembrane domains, and 8 on the intradiscal side. Forty-three of the 150 patients (29%) carry 1 of these mutations, and no patient has more than 1 mutation. In every family with a mutation so far analyzed, the mutation cosegregates with the disease. They found one instance of a mutation in an affected patient that was absent in both unaffected parents (i.e., a new germ-line mutation), indicating that some isolate cases of retinitis pigmentosa carry a mutation of the rhodopsin gene.

  15. Novel deletions involving the USH2A gene in patients with Usher syndrome and retinitis pigmentosa

    PubMed Central

    García-García, Gema; Jaijo, Teresa; Aparisi, Maria J.; Larrieu, Lise; Faugère, Valérie; Blanco-Kelly, Fiona; Ayuso, Carmen; Roux, Anne-Francoise; Millán, José M.

    2014-01-01

    Purpose The aim of the present work was to identify and characterize large rearrangements involving the USH2A gene in patients with Usher syndrome and nonsyndromic retinitis pigmentosa. Methods The multiplex ligation-dependent probe amplification (MLPA) technique combined with a customized array-based comparative genomic hybridization (aCGH) analysis was applied to 40 unrelated patients previously screened for point mutations in the USH2A gene in which none or only one pathologic mutation was identified. Results We detected six large deletions involving USH2A in six out of the 40 cases studied. Three of the patients were homozygous for the deletion, and the remaining three were compound heterozygous with a previously identified USH2A point mutation. In five of these cases, the patients displayed Usher type 2, and the remaining case displayed nonsyndromic retinitis pigmentosa. The exact breakpoint junctions of the deletions found in USH2A in four of these cases were characterized. Conclusions Our study highlights the need to develop improved efficient strategies of mutation screening based upon next generation sequencing (NGS) that reduce cost, time, and complexity and allow simultaneous identification of all types of disease-causing mutations in diagnostic procedures. PMID:25352746

  16. FEATURES OF THE MACULA AND CENTRAL VISUAL FIELD AND FIXATION PATTERN IN PATIENTS WITH RETINITIS PIGMENTOSA.

    PubMed

    Sayman Muslubas, Isil; Karacorlu, Murat; Arf, Serra; Hocaoglu, Mumin; Ersoz, Mehmet Giray

    2017-02-07

    To evaluate macular features and fixation pattern in patients with retinitis pigmentosa (RP) compared with healthy controls, using spectral-domain optical coherence tomography and MP-1 microperimetry. Eighty-one eyes of 81 patients with RP and 90 eyes of 90 healthy subjects were assessed. The central foveal thickness, subfoveal choroidal thickness, ellipsoid zone length, and the mean retinal sensitivities and fixation characteristics were evaluated by spectral-domain optical coherence tomography and MP-1 microperimetry. Compared with healthy subjects, patients with central macular thinning had lower best corrected visual acuity, central foveal thickness, ellipsoid zone length, retinal sensitivity, and visual field than patients with cystoid macular edema or no macular change (all P < 0.001). Correlations between fixation characteristics and best corrected visual acuity, central foveal thickness, ellipsoid zone length, retinal sensitivity, and visual field were statistically significant (all P < 0.001). Patients with no macular change had more centralized and stabilized fixation than patients with central foveal thinning and cystoid macular edema. The spectrum of macular features from the nearly normal retina to complete chorioretinal atrophy can be seen in RP patients without associations with age or duration of symptoms. Unlike other macular degenerations, most patients with RP obtained at least a central 2° of visual field, with foveal and stable fixation.

  17. Retinal histopathology in eyes from patients with autosomal dominant retinitis pigmentosa caused by rhodopsin mutations.

    PubMed

    Bonilha, Vera L; Rayborn, Mary E; Bell, Brent A; Marino, Meghan J; Beight, Craig D; Pauer, Gayle J; Traboulsi, Elias I; Hollyfield, Joe G; Hagstrom, Stephanie A

    2015-12-01

    To evaluate the histopathology in donor eyes from patients with autosomal dominant retinitis pigmentosa (ADRP) caused by p.P23H, p.P347T and p.P347L rhodopsin ( RHO ) gene mutations. Eyes from a 72-year-old male (donor 1), an 83-year-old female (donor 2), an 80-year-old female (donor 3), and three age-similar normal eyes were examined macroscopically, by scanning laser ophthalmoscopy and optical coherence tomography imaging. Perifoveal and peripheral pieces were processed for microscopy and immunocytochemistry with markers for photoreceptor cells. DNA analysis revealed RHO mutations c.68C>A (p.P23H) in donor 1, c.1040C>T (p.P347L) in donor 2 and c.1039C>A (p.P347T) in donor 3. Histology of the ADRP eyes showed retinas with little evidence of stratified nuclear layers in the periphery and a prominent inner nuclear layer present in the perifoveal region in the p.P23H and p.P347T eyes, while it was severely atrophic in the p.P347L eye. The p.P23H and p.P347T mutations cause a profound loss of rods in both the periphery and perifovea, while the p.P347L mutation displays near complete absence of rods in both regions. All three rhodopsin mutations caused a profound loss of cones in the periphery. The p.P23H and p.P347T mutations led to the presence of highly disorganized cones in the perifovea. However, the p.P347L mutation led to near complete absence of cones also in the perifovea. Our results support clinical findings indicating that mutations affecting residue P347 develop more severe phenotypes than those affecting P23. Furthermore, our results indicate a more severe phenotype in the p.P347L retina as compared to the p.P347T retina.

  18. Retinitis Pigmentosa and Education Issues

    ERIC Educational Resources Information Center

    Brown, Thomas J.

    2005-01-01

    Retinitis Pigmentosa includes a number of inherited diseases which usually result in blindness. The disease is progressive in nature and begins with the deterioration of cells in the eye responsible for peripheral vision. As the condition worsens there is a gradual loss of peripheral vision and night blindness. Proper educational planning requires…

  19. Novel mutations in the NRL gene and associated clinical findings in patients with dominant retinitis pigmentosa.

    PubMed

    DeAngelis, Margaret M; Grimsby, Jonna L; Sandberg, Michael A; Berson, Eliot L; Dryja, Thaddeus P

    2002-03-01

    To search for mutations in the neural retina leucine zipper (NRL) gene in patients with dominant retinitis pigmentosa and to compare the severity of disease in these patients with that observed previously in patients with dominant rhodopsin mutations. Single-strand conformation analysis was used to survey 189 unrelated patients for mutations. The available relatives of index patients with mutations were also evaluated. In our clinical examination of patients, we measured visual acuity, final dark-adaptation threshold equivalent visual field diameter, and electroretinogram amplitudes among other parameters of visual function. We compared the clinical findings with those obtained earlier from similar evaluations of a group of 39 patients with the dominant rhodopsin mutation Pro23His and a group of 25 patients with the dominant rhodopsin mutation Pro347Leu. We identified 3 novel missense mutations in a total of 4 unrelated patients with dominant retinitis pigmentosa: Ser50Pro, Ser50Leu (2 patients), and Pro51Thr. Each mutation cosegregated with dominant retinitis pigmentosa. None of these mutations were found among 91 unrelated control individuals. The visual acuities among the 4 index patients and 3 relatives with NRL mutations who were clinically evaluated ranged from 20/20 (in a 9-year-old patient) to 20/200 (in a 73-year-old patient). All patients had bone-spicule pigment deposits in their fundi. Average rod-plus-cone and cone-isolated electroretinogram amplitudes were both decreased by 99% or more compared with normal amplitudes. The dark-adaptation thresholds, equivalent visual field diameters, and electroretinogram amplitudes (all corrected for age and refractive error) indicated that the disease caused by the NRL mutations was more severe than that caused by the dominant rhodopsin mutation Pro23His and was similar in severity to that produced by the rhodopsin mutation Pro347Leu. The 3 novel NRL mutations we discovered bring the total number of reported

  20. A novel start codon mutation of the MERTK gene in a patient with retinitis pigmentosa.

    PubMed

    Jinda, Worapoj; Poungvarin, Naravat; Taylor, Todd D; Suzuki, Yutaka; Thongnoppakhun, Wanna; Limwongse, Chanin; Lertrit, Patcharee; Suriyaphol, Prapat; Atchaneeyasakul, La-Ongsri

    2016-01-01

    Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of inherited retinal degenerations characterized by progressive loss of photoreceptor cells and RPE functions. More than 70 causative genes are known to be responsible for RP. This study aimed to identify the causative gene in a patient from a consanguineous family with childhood-onset severe retinal dystrophy. To identify the defective gene, whole exome sequencing was performed. Candidate causative variants were selected and validated using Sanger sequencing. Segregation analysis of the causative gene was performed in additional family members. To verify that the mutation has an effect on protein synthesis, an expression vector containing the first ten amino acids of the mutant protein fused with the DsRed2 fluorescent protein was constructed and transfected into HEK293T cells. Expression of the fusion protein in the transfected cells was measured using fluorescence microscopy. By filtering against public variant databases, a novel homozygous missense mutation (c.3G>A) localized in the start codon of the MERTK gene was detected as a potentially pathogenic mutation for autosomal recessive RP. The c.3G>A mutation cosegregated with the disease phenotype in the family. No expression of the first ten amino acids of the MerTK mutant fused with the DsRed2 fluorescent protein was detected in HEK293T cells, indicating that the mutation affects the translation initiation site of the gene that may lead to loss of function of the MerTK signaling pathway. We report a novel missense mutation (c.3G>A, p.0?) in the MERTK gene that causes severe vision impairment in a patient. Taken together with previous reports, our results expand the spectrum of MERTK mutations and extend our understanding of the role of the MerTK protein in the pathogenesis of retinitis pigmentosa.

  1. A novel start codon mutation of the MERTK gene in a patient with retinitis pigmentosa

    PubMed Central

    Jinda, Worapoj; Poungvarin, Naravat; Taylor, Todd D.; Suzuki, Yutaka; Thongnoppakhun, Wanna; Limwongse, Chanin; Lertrit, Patcharee; Suriyaphol, Prapat

    2016-01-01

    Purpose Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of inherited retinal degenerations characterized by progressive loss of photoreceptor cells and RPE functions. More than 70 causative genes are known to be responsible for RP. This study aimed to identify the causative gene in a patient from a consanguineous family with childhood-onset severe retinal dystrophy. Methods To identify the defective gene, whole exome sequencing was performed. Candidate causative variants were selected and validated using Sanger sequencing. Segregation analysis of the causative gene was performed in additional family members. To verify that the mutation has an effect on protein synthesis, an expression vector containing the first ten amino acids of the mutant protein fused with the DsRed2 fluorescent protein was constructed and transfected into HEK293T cells. Expression of the fusion protein in the transfected cells was measured using fluorescence microscopy. Results By filtering against public variant databases, a novel homozygous missense mutation (c.3G>A) localized in the start codon of the MERTK gene was detected as a potentially pathogenic mutation for autosomal recessive RP. The c.3G>A mutation cosegregated with the disease phenotype in the family. No expression of the first ten amino acids of the MerTK mutant fused with the DsRed2 fluorescent protein was detected in HEK293T cells, indicating that the mutation affects the translation initiation site of the gene that may lead to loss of function of the MerTK signaling pathway. Conclusions We report a novel missense mutation (c.3G>A, p.0?) in the MERTK gene that causes severe vision impairment in a patient. Taken together with previous reports, our results expand the spectrum of MERTK mutations and extend our understanding of the role of the MerTK protein in the pathogenesis of retinitis pigmentosa. PMID:27122965

  2. Molecular study of the rhodopsin gene in retinitis pigmentosa patients in the Basque Country.

    PubMed Central

    Alvarez, A I; Arostegui, E; Martin, R; Duran, M; Onaindia, M L; Molina, M; Tejada, M I

    1998-01-01

    Retinitis pigmentosa (RP) is a degenerative disorder affecting the outer segment of the retina and leading to night blindness and progressive visual field loss. The rhodopsin gene encodes a photolabile pigment located in the rod outer segments constituting around 80-90% of its protein content and is the initiation point for the visual cascade upon absorption of a single photon. Seventy-five unrelated, isolated RP families in the Basque Country, with at least one affected member, were diagnosed at our hospital after ophthalmic examination and electroretinogram analysis. The patients received genetic counselling according to their individual case based on their clinical diagnosis. The modes of inheritance found from pedigree studies were the following: 20% (15/75) were classified as autosomal dominant retinitis pigmentosa (ADRP), 17.33% (13/75) were autosomal recessive (ARRP), 2.66% (2/75) were unclassified (NC), and 60% (45/75) were sporadic cases (SCRP). From these families, 75 unrelated and affected index cases together with 22 affected relatives and 42 unaffected relatives were screened for mutations in the rhodopsin gene by GC clamped denaturing gradient gel electrophoresis. Our results showed that five ADRP, three ARRP, 15 SCRP, and one NC families had alterations in this gene. Only three of these alterations, that is 4% (3/75) (95% CL 0-8), appeared to be responsible for the disease. This represents a lower percentage than the 10% previously reported. PMID:9610801

  3. Molecular study of the rhodopsin gene in retinitis pigmentosa patients in the Basque Country.

    PubMed

    Alvarez, A I; Arostegui, E; Martin, R; Duran, M; Onaindia, M L; Molina, M; Tejada, M I

    1998-05-01

    Retinitis pigmentosa (RP) is a degenerative disorder affecting the outer segment of the retina and leading to night blindness and progressive visual field loss. The rhodopsin gene encodes a photolabile pigment located in the rod outer segments constituting around 80-90% of its protein content and is the initiation point for the visual cascade upon absorption of a single photon. Seventy-five unrelated, isolated RP families in the Basque Country, with at least one affected member, were diagnosed at our hospital after ophthalmic examination and electroretinogram analysis. The patients received genetic counselling according to their individual case based on their clinical diagnosis. The modes of inheritance found from pedigree studies were the following: 20% (15/75) were classified as autosomal dominant retinitis pigmentosa (ADRP), 17.33% (13/75) were autosomal recessive (ARRP), 2.66% (2/75) were unclassified (NC), and 60% (45/75) were sporadic cases (SCRP). From these families, 75 unrelated and affected index cases together with 22 affected relatives and 42 unaffected relatives were screened for mutations in the rhodopsin gene by GC clamped denaturing gradient gel electrophoresis. Our results showed that five ADRP, three ARRP, 15 SCRP, and one NC families had alterations in this gene. Only three of these alterations, that is 4% (3/75) (95% CL 0-8), appeared to be responsible for the disease. This represents a lower percentage than the 10% previously reported.

  4. Age at onset curves of retinitis pigmentosa.

    PubMed

    Tsujikawa, Motokazu; Wada, Yuko; Sukegawa, Marie; Sawa, Miki; Gomi, Fumi; Nishida, Kohji; Tano, Yasuo

    2008-03-01

    To calculate age at onset curves of retinitis pigmentosa (RP) to resolve the difficulty in calculating the recurrence risk in a family. Retinitis pigmentosa is a common hereditary retinal disease that leads to blindness. It is a slow-onset disease, and family members of patients sometimes develop RP later. We studied 370 patients with typical RP. The age at onset was defined as when the patient's RP was diagnosed by an ophthalmologist. After confirmation that the age at onset came from normal distribution, we drew the age at onset curves. The average age when patients were diagnosed with RP was 35.1 years, and the median age was 36.5. The onset ratio straightly increased with age until 65 years, so the onset ratio was relatively low at young ages. The age at onset curves are quite simple and useful tools that facilitate counseling at an RP clinic. Without them, the recurrence risk would be misleading.

  5. Precision Medicine: Genetic Repair of Retinitis Pigmentosa in Patient-Derived Stem Cells.

    PubMed

    Bassuk, Alexander G; Zheng, Andrew; Li, Yao; Tsang, Stephen H; Mahajan, Vinit B

    2016-01-27

    Induced pluripotent stem cells (iPSCs) generated from patient fibroblasts could potentially be used as a source of autologous cells for transplantation in retinal disease. Patient-derived iPSCs, however, would still harbor disease-causing mutations. To generate healthy patient-derived cells, mutations might be repaired with new gene-editing technology based on the bacterial system of clustered regularly interspersed short palindromic repeats (CRISPR)/Cas9, thereby yielding grafts that require no patient immunosuppression. We tested whether CRISPR/Cas9 could be used in patient-specific iPSCs to precisely repair an RPGR point mutation that causes X-linked retinitis pigmentosa (XLRP). Fibroblasts cultured from a skin-punch biopsy of an XLRP patient were transduced to produce iPSCs carrying the patient's c.3070G > T mutation. The iPSCs were transduced with CRISPR guide RNAs, Cas9 endonuclease, and a donor homology template. Despite the gene's repetitive and GC-rich sequences, 13% of RPGR gene copies showed mutation correction and conversion to the wild-type allele. This is the first report using CRISPR to correct a pathogenic mutation in iPSCs derived from a patient with photoreceptor degeneration. This important proof-of-concept finding supports the development of personalized iPSC-based transplantation therapies for retinal disease.

  6. Survey in to the prevalence of hearing loss in patients diagnosed with retinitis pigmentosa.

    PubMed

    Iwasaki, Satoshi; Maruyama, Yuuka; Hotta, Yoshihiro; Hashimoto, Yasuyuki; Nagura, Mitsuyoshi

    2004-01-01

    Sensorineural hearing loss is the most common disease associated with systemic retinitis pigmentosa (RP). We have conducted an epidemiological study to assess the correlation of age at onset of visual symptoms and hearing loss associated with RP. Epidemiological data was derived from a questionnaire-based study of patients who are registered members of the Japanese Retinitis Pigmentosa Society (n = 3200). The questionnaire was mailed to these patients in 2002, and information was requested regarding age at onset of visual disturbance, awareness of hearing loss and the presence of progressive hearing loss, age at onset of hearing loss, awareness of tinnitus, and history of audiometric examination and hearing aid usage. 26.1% of the questionnaires were returned, and data for 828 patients with RP diagnosed by an ophthalmologist were evaluated. Cochlear symptoms were reported by 356 patients (43.0% of the total population), with hearing loss in 29.5%, tinnitus in 31.5% and hearing loss and tinnitus in 39.3% of the 356 patients. Of these 356 patients, progressive hearing loss was reported by 44.9% and was independent of age at onset of cochlear symptoms. The mean age at onset of visual symptoms was higher for patients with progressive hearing loss, and a significant correlation was found between the age at onset of visual symptoms and hearing loss for patients who were older at onset of the symptoms (>30 years of age). Onset of hearing loss occurs later and hearing loss is also more progressive for patients with late onset of RP. This suggests that particular care regarding hearing loss is necessary for this patient population, and that cooperation between opthalmologists and otologists is required for diagnosis of RP-hearing impairment-associated syndromes in this group of patients.

  7. Course of Ocular Function in PRPF31 Retinitis Pigmentosa.

    PubMed

    Hafler, Brian P; Comander, Jason; Weigel DiFranco, Carol; Place, Emily M; Pierce, Eric A

    2016-01-01

    Mutations in pre-mRNA splicing factors are the second most common cause of autosomal dominant retinitis pigmentosa, and a major cause of vision loss. The development of gene augmentation therapy for disease caused by mutations in PRPF31 necessitates defining pretreatment characteristics and disease progression of patients with PRPF31-related retinitis pigmentosa. We show rates of decline of visual field area -6.9% per year and 30-Hz flicker cone response of -9.2% per year, which are both similar to observed rates for retinitis pigmentosa. We hypothesize that RNA splicing factor retinitis pigmentosa will be amenable to treatment by AAV-mediated gene therapy, and that understanding the clinical progression rates of PRPF31 retinitis pigmentosa will help with the design of gene therapy clinical trials.

  8. Long-term follow-up of retinitis pigmentosa patients with multifocal electroretinography.

    PubMed

    Nagy, Ditta; Schönfisch, Birgitt; Zrenner, Eberhart; Jägle, Herbert

    2008-10-01

    To study the rate of multifocal electroretinographic (mfERG) response amplitude changes and their relation to other parameters of disease development in retinitis pigmentosa (RP). Twenty-three patients (9 men and 14 women) with clinically defined RP were included in the study. Disease progression was monitored during a period of up to 10 years by psychophysical techniques and Ganzfeld electroretinography. In addition, ERGs were recorded with a mfERG imaging system (VERIS; Electro-Diagnostic Imaging, Inc., Redwood City, CA). The black and white stimulus consisted of 61 hexagons covering a visual field of approximately 60 degrees x 55 degrees . Responses were analyzed according to concentric ring averages. The progression of visual field loss for target III4e was approximately 14.5%. Using the same type of regression model, the yearly progression according to the mfERG values was found to be approximately 6% to 10% in the outer three rings. Visual acuity (median 0.8) correlated well with the amplitude of the central segment of the mfERGs, ring 5 amplitudes of the mfERG strongly correlated with the scotopic Ganzfeld ERG mixed cone-rod response amplitude. However, in advanced cases, reliable mfERG responses could still be recorded, even if the ISCEV scotopic Ganzfeld ERG was not reproducible. MfERG ring 5 amplitudes as well as the Ganzfeld ERG mixed cone-rod response amplitude showed only a mild correlation with visual field area. The mfERG allows long-term follow-up of disease progression in retinitis pigmentosa. It does not replace, but complements psychophysical methods and could be used as an objective outcome measure in upcoming treatment studies involving patients with advanced retinal diseases.

  9. Retinitis Pigmentosa and Other Dystrophies.

    PubMed

    Mrejen, Sarah; Audo, Isabelle; Bonnel, Sébastien; Sahel, José-Alain

    2017-01-01

    Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations characterized by progressive degeneration of rod and cone cells that affects predominantly peripheral visual fields. Macular edema may cause additional central visual acuity decrease. Cystoid macular edema (CME) is one of the few treatable causes of visual loss in RP. The prevalence of CME in RP has been found to be between 10 and 20% on fluorescein angiography-based studies, and as high as 49% on reports based on optical coherence tomography. Macular edema can manifest at any stage of the disease and may be unilateral or bilateral. It can be found in any genetic form, but is more often associated with RP caused by CRB1 mutations. The origin of macular edema in RP patients still remains poorly understood. Some mechanisms have been suggested, including antiretinal antibodies (retinal, carbonic anhydrase, and enolase antibodies), vitreous traction, retinal pigment epithelium dysfunction, and Müller cell edema. There is no gold standard therapeutic strategy. Drug therapy is the primary treatment. Systemic carbonic anhydrase inhibitors, such as oral acetazolamide or topical dorzolamide, are still the mainstays of initial therapy. If CME is refractory to acetazolamide, intravitreal corticosteroid injections may be a therapeutic option. However, antivascular endothelium growth factor injections have limited effect and should be avoided. Vitrectomy has also been evaluated, but its exact role remains to be determined. The benefits of these therapies are variable among patients. The establishment of therapeutic approaches is limited by our poor understanding of the pathophysiology of CME in patients with RP. Autoimmune retinopathies (AIRs) are a group of rare diseases characterized by acute or subacute progressive vision loss and are thought to be mediated by autoantibodies specific to retinal antigens. The AIRs encompass paraneoplastic syndromes, such as cancer-associated retinopathy and

  10. Bilateral Concordance of the Fundus Hyperautofluorescent Ring in Typical Retinitis Pigmentosa Patients.

    PubMed

    Sujirakul, Tharikarn; Davis, Richard; Erol, Deniz; Zhang, Lijuan; Schillizzi, Giuseppe; Royo-Dujardin, Leticia; Shen, Sherry; Tsang, Stephen

    2015-06-01

    It has long been assumed that in retinitis pigmentosa, disease presentation and progression are symmetrical. This study investigated whether hyperautofluorescent ring size, one known marker of disease progression, is symmetrical in typical RP patients. A total of 88 patients with typical retinitis pigmentosa were enrolled in the study. Each presented with a hyperautofluorescent ring when imaged at baseline with fundus autofluorescence (AF). Vertical and horizontal diameters were analyzed according to mode of inheritance and age group. Seven of 88 patients had data missing in one eye and were excluded from further analysis. There was no significant relationship between hyperautofluorescent ring diameter and inheritance mode. There was a tendency toward smaller ring size with age and 3.7% of subjects displayed marked asymmetry in ring size between right and left eyes, although their electroretinogram results did not differ. Overall, when patients were considered as a group, there was a high correlation between right and left eyes' horizontal and vertical diameters (r=0.99, p<0.0001; r=0.98, p<0.0001). Comparing individual patients' eyes, and accounting for measurement error, a smaller majority of patients displayed symmetry of the hyperautofluorescent ring in both dimensions (85.7% in the vertical dimension, 87.3% in the horizontal dimension). This study confirmed the highly symmetrical nature of the hyperautofluorescent ring in RP patients, except in a small subgroup. AF results, which provide less variability per image, and are consistently interpreted between different observers, may be a more sensitive and reliable method for testing symmetry than many functional tests.

  11. Bilateral Concordance of the Fundus Hyperautofluorescent Ring in Typical Retinitis Pigmentosa Patients

    PubMed Central

    Sujirakul, Tharikarn; Davis, Richard; Erol, Deniz; Zhang, Lijuan; Schillizzi, Giuseppe; Royo-Dujardin, Leticia; Shen, Sherry; Tsang, Stephen

    2016-01-01

    Background It has long been assumed that in retinitis pigmentosa, disease presentation and progression are symmetrical. This study investigated whether hyperautofluorescent ring size, one known marker of disease progression, is symmetrical in typical RP patients. Materials and Methods A total of 88 patients with typical retinitis pigmentosa were enrolled in the study. Each presented with a hyperautofluorescent ring when imaged at baseline with fundus autofluorescence (AF). Vertical and horizontal diameters were analyzed according to mode of inheritance and age group. Seven of 88 patients had data missing in one eye and were excluded from further analysis. Results There was no significant relationship between hyperautofluorescent ring diameter and inheritance mode. There was a tendency toward smaller ring size with age and 3.7% of subjects displayed marked asymmetry in ring size between right and left eyes, although their electroretinogram results did not differ. Overall, when patients were considered as a group, there was a high correlation between right and left eyes’ horizontal and vertical diameters (r = 0.99, p<0.0001; r = 0.98, p<0.0001). Comparing individual patients’ eyes, and accounting for measurement error, a smaller majority of patients displayed symmetry of the hyperautofluorescent ring in both dimensions (85.7% in the vertical dimension, 87.3% in the horizontal dimension). Conclusion This study confirmed the highly symmetrical nature of the hyperautofluorescent ring in RP patients, except in a small subgroup. AF results, which provide less variability per image, and are consistently interpreted between different observers, may be a more sensitive and reliable method for testing symmetry than many functional tests. PMID:24111858

  12. Correlation between contrast sensitivity and visual acuity in retinitis pigmentosa patients.

    PubMed

    Akeo, Kiyoshi; Hiida, Yoshiki; Saga, Masamichi; Inoue, Rikako; Oguchi, Yoshihisa

    2002-01-01

    High-contrast figures such as Landolt rings are insufficient to evaluate the function of the foveal cones of retinitis pigmentosa (RP) patients. We investigated the correlation between visual function as determined with Landolt rings and with the Vistech Contrast Sensitivity Function Test (VCTS) at various spatial frequencies, in addition to the Cambridge Low Contrast Grating (CLCG). The study included 30 retinitis pigmentosa patients (53 eyes). All patients were assessed with Landolt rings, the Vistech method, and the CLCG. We estimated the relative contribution of contrast sensitivity to visual acuity by VCTS at each spatial frequency and by CLCG by simple linear regression analysis. The results of the regression analysis of VCTS at 1.5, 3.0, and 6.0 cycles/degree showed a significant correlation between Landolt rings and VCTS and between CLCG and VCTS that was strongest at 6.0 cycles/degree. There was no significant correlation between Landolt rings and VCTS or between CLCG and VCTS at 12.0 and 18.0 cycles/degree. Patients with a visual acuity of 20/25 and CLCG greater than 100 were divided into two groups according to their contrast sensitivity at 18.0 cycles/degree on VCTS. The VCTS at the highest frequency was useful for evaluating the foveal visual function in RP patients having good visual acuity with the Landolt rings. Thus, contrast sensitivity should be useful in detecting minute impairment or improvement of visual function in RP. Copyright 2002 S. Karger AG, Basel

  13. Further screening of the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa

    SciTech Connect

    Vaithinathan, R.; Berson, E.L.; Dryja, T.P. )

    1994-05-15

    Here the authors report 8 novel mutations and 8 previously reported mutations found from further analysis of the rhodopsin gene in a large set of additional patients with autosomal dominant retinitis pigmentosa. Leukocyte DNA was purified from 122 unrelated patients with autosomal dominant retinitis pigmentosa who were not included in previous analyses. The coding region and splice donor and acceptor sites of the rhodopsin gene were screened for mutations using single-strand conformation polymorphism analysis and direct genomic sequencing. They found 29 patients with varient bands that were due to mutations. Sequence analysis showed that 20 cases each had 1 of 9 previously published mutations: Pro23His, Thr58Arg, Gly89Asp, Pro171Leu, Glu181Lys, Pro347Leu, Phe45Leu, Arg135Trp, and Lys296Glu. In 9 other cases, they found 8 novel mutations. One was a 3-bp deletion (Cys264-del), and the rest were point mutations resulting in an altered amino acid: Gly51Arg (GGC [yields] CGC), Cys110Tyr (TCG [yields] TAC), Gly114Asp (GGC [yields] GAC), Ala164Glu (GCG [yields] GAG), Pro171Ser (CCA [yields] TCA), Val345Leu (GTG [yields] CTG), and Pro347Gln (CCG [yields] CAG). Each of these novel mutations was found in only one family except for Gly51Arg, which was found in two. In every family tested, the mutation cosegregated with the disease. However, in pedigree D865 only one affected member was available for analysis. About two-thirds of the mutations affect amino acids in transmembrane domains, yet only one-half of opsin's residues are in these regions. One-third of the mutations alter residues in the extracellular/intradiscal space, which includes only 25% of the protein.

  14. Spectral Domain optical coherence tomography findings in patients with retinitis pigmentosa.

    PubMed

    Chebil, Ahmed; Touati, Salma; Maamouri, Rym; Kort, Fedra; El Matri, Leila

    2016-04-01

    Background Maculopathy is a common complication of retinitis pigmentosa (RP), and compromise the visual acuity of RP patients even in the less advanced stages. Aim To report the morphological macular findings detected by spectral domain optical coherence tomography (SD-OCT) and to determine their prevalence in patients with retinitis pigmentosa (RP). Methods  SD-OCT scans from 100 patients (196 eyes) affected by RP were reviewed. Results We noted a normal macula appearance in 48.5%, macular edema in 14.5% and macular atrophy in 37%. Mean central macular thickness was 167.79 microns and we did not note any statistically significant correlation between visual acuity and foveal thickness. Visual acuity was statistically better in eyes with a larger number of hyper-reflective layers (p<0.001) and in eyes with photoreceptor inner/outer (IS/OS) segment junction distinct (p<0.001). We have identified three types of tomographic macular edema: a cystoids macular edema in 6.8%, a tractional edema in 8.2% and mixed edema in 1%. We identified two tomographic types of macular atrophy: a central- foveal atrophy in 34 eyes (11.6%) and diffuse atrophy in 38 eyes (12.9%). Epiretinal membrane was present in 24 eyes (8.2%). Conclusions The OCT contributes to the analysis of epidemiological and morphological of different macular involvement in RP. OCT has a prognostic value, which essentially depends on the morphology of the IS/OS line and number of hyper-reflective layers.

  15. Novel Mutations of RPGR in Chinese Retinitis Pigmentosa Patients and the Genotype-Phenotype Correlation

    PubMed Central

    You, Debo; Wu, Lemeng; Chen, Ningning; Li, Aijun; Li, Genlin; Ma, Zhizhong

    2014-01-01

    X-linked Retinitis Pigmentosa (XLRP) accounts for 10–20% of all RP cases, and represents the most severe subtype of this disease. Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) gene are the most common causes of XLRP, accounting for over 70–75% of all XLRP cases. In this work, we analyzed all the exons of RPGR gene with Sanger sequencing in seven Chinese XLRP families, two of these with a provisional diagnosis of adRP but without male-to-male transmission. Three novel deletions (c.2233_34delAG; c.2236_37delGA and c.2403_04delAG) and two known nonsense mutations (c.851C→G and c.2260G→T) were identified in five families. Two novel deletions (c.2233_34delAG and c.2236_37delGA) resulted in the same frame shift (p.E746RfsX22), created similar phenotype in Family 3 and 4. The novel deletion (c.2403_04delAG; p.E802GfsX31) resulted in both XLRP and x-linked cone-rod dystrophy within the male patients of family 5, which suggested the presence of either genetic or environmental modifiers, or both, play a substantial role in disease expression. Genotype-phenotype correlation analysis suggested that (1) both patients and female carriers with mutation in Exon 8 (Family 1) manifest more severe disease than did those with ORF15 mutations (Family 2&3&4); (2) mutation close to downstream of ORF15 (Family 5) demonstrate the early preferential loss of cone function with moderate loss of rod function. PMID:24454928

  16. Novel mutations of RPGR in Chinese retinitis pigmentosa patients and the genotype-phenotype correlation.

    PubMed

    Yang, Liping; Yin, Xiaobei; Feng, Lina; You, Debo; Wu, Lemeng; Chen, Ningning; Li, Aijun; Li, Genlin; Ma, Zhizhong

    2014-01-01

    X-linked Retinitis Pigmentosa (XLRP) accounts for 10-20% of all RP cases, and represents the most severe subtype of this disease. Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) gene are the most common causes of XLRP, accounting for over 70-75% of all XLRP cases. In this work, we analyzed all the exons of RPGR gene with Sanger sequencing in seven Chinese XLRP families, two of these with a provisional diagnosis of adRP but without male-to-male transmission. Three novel deletions (c.2233_34delAG; c.2236_37delGA and c.2403_04delAG) and two known nonsense mutations (c.851C→G and c.2260G→T) were identified in five families. Two novel deletions (c.2233_34delAG and c.2236_37delGA) resulted in the same frame shift (p.E746RfsX22), created similar phenotype in Family 3 and 4. The novel deletion (c.2403_04delAG; p.E802GfsX31) resulted in both XLRP and x-linked cone-rod dystrophy within the male patients of family 5, which suggested the presence of either genetic or environmental modifiers, or both, play a substantial role in disease expression. Genotype-phenotype correlation analysis suggested that (1) both patients and female carriers with mutation in Exon 8 (Family 1) manifest more severe disease than did those with ORF15 mutations (Family 2&3&4); (2) mutation close to downstream of ORF15 (Family 5) demonstrate the early preferential loss of cone function with moderate loss of rod function.

  17. Clinical presentation and visual status of retinitis pigmentosa patients: a multicenter study in southwestern Nigeria

    PubMed Central

    Onakpoya, Oluwatoyin Helen; Adeoti, Caroline Olufunlayo; Oluleye, Tunji Sunday; Ajayi, Iyiade Adeseye; Majengbasan, Timothy; Olorundare, Olayemi Kolawole

    2016-01-01

    Background To review the visual status and clinical presentation of patients with retinitis pigmentosa (RP). Methodology Multicenter, retrospective, and analytical review was conducted of the visual status and clinical characteristics of patients with RP at first presentation from January 2007 to December 2011. Main outcome measure was the World Health Organization’s visual status classification in relation to sex and age at presentation. Data analysis by SPSS (version 15) and statistical significance was assumed at P<0.05. Results One hundred and ninety-two eyes of 96 patients with mean age of 39.08±18.5 years and mode of 25 years constituted the study population; 55 (57.3%) were males and 41 (42.7%) females. Loss of vision 67 (69.8%) and night blindness 56 (58.3%) were the leading symptoms. Twenty-one (21.9%) patients had a positive family history, with RP present in their siblings 15 (71.4%), grandparents 11 (52.3%), and parents 4 (19.4%). Forty (41.7%) were blind at presentation and 23 (24%) were visually impaired. Blindness in six (15%) patients was secondary to glaucoma. Retinal vascular narrowing and retinal pigmentary changes of varying severity were present in all patients. Thirty-five (36.5%) had maculopathy, 36 (37.5%) refractive error, 19 (20%) lenticular opacities, and eleven (11.5%) had glaucoma. RP was typical in 85 patients (88.5%). Older patients had higher rates of blindness at presentation (P=0.005); blindness and visual impairment rate at presentation were higher in males than females (P=0.029). Conclusion Clinical presentation with advanced diseases, higher blindness rate in older patients, sex-related difference in blindness/visual impairment rates, as well as high glaucoma blindness in RP patients requires urgent attention in southwestern Nigeria. PMID:27601870

  18. Clinical presentation and visual status of retinitis pigmentosa patients: a multicenter study in southwestern Nigeria.

    PubMed

    Onakpoya, Oluwatoyin Helen; Adeoti, Caroline Olufunlayo; Oluleye, Tunji Sunday; Ajayi, Iyiade Adeseye; Majengbasan, Timothy; Olorundare, Olayemi Kolawole

    2016-01-01

    To review the visual status and clinical presentation of patients with retinitis pigmentosa (RP). Multicenter, retrospective, and analytical review was conducted of the visual status and clinical characteristics of patients with RP at first presentation from January 2007 to December 2011. Main outcome measure was the World Health Organization's visual status classification in relation to sex and age at presentation. Data analysis by SPSS (version 15) and statistical significance was assumed at P<0.05. One hundred and ninety-two eyes of 96 patients with mean age of 39.08±18.5 years and mode of 25 years constituted the study population; 55 (57.3%) were males and 41 (42.7%) females. Loss of vision 67 (69.8%) and night blindness 56 (58.3%) were the leading symptoms. Twenty-one (21.9%) patients had a positive family history, with RP present in their siblings 15 (71.4%), grandparents 11 (52.3%), and parents 4 (19.4%). Forty (41.7%) were blind at presentation and 23 (24%) were visually impaired. Blindness in six (15%) patients was secondary to glaucoma. Retinal vascular narrowing and retinal pigmentary changes of varying severity were present in all patients. Thirty-five (36.5%) had maculopathy, 36 (37.5%) refractive error, 19 (20%) lenticular opacities, and eleven (11.5%) had glaucoma. RP was typical in 85 patients (88.5%). Older patients had higher rates of blindness at presentation (P=0.005); blindness and visual impairment rate at presentation were higher in males than females (P=0.029). Clinical presentation with advanced diseases, higher blindness rate in older patients, sex-related difference in blindness/visual impairment rates, as well as high glaucoma blindness in RP patients requires urgent attention in southwestern Nigeria.

  19. Photopic ERG components in retinitis pigmentosa.

    PubMed

    Anastasi, M; Lauricella, M; Ponte, F

    1992-04-01

    The persistence of a residual flicker electroretinogram 20 Hz response in many cases of retinitis pigmentosa, when the Oscillatory Potentials (OPs) were no longer recordable, led the authors to an investigation by Fourier analysis. The study was carried out in 33 patients affected by different hereditary forms of retinitis pigmentosa revealing recordable 20 Hz flash ERG responses. We applied the Fourier analysis to this ERG response and compared the weight percentage of the first two components to the OP added amplitude. The analysis showed that the 20 Hz flash ERG response contains only the first harmonic in patients with no recordable OPs and both harmonics in patients with recordable OPs. This relationship between OPs and 20 Hz second component, that is possibly related to the activity of inner retina as well as the OPs, can demonstrate an alteration of the inner retina which evolves with distinct electrophysiological features from the ERG photoreceptor impairment.

  20. The Relationship of Central Foveal Thickness to Urinary Iodine Concentration in Retinitis Pigmentosa Patients with or without Cystoid Macular Edema

    PubMed Central

    Sandberg, Michael A.; Pearce, Elizabeth N.; Harper, Shyana; Weigel-DiFranco, Carol; Hart, Lois; Rosner, Bernard; Berson, Eliot L.

    2014-01-01

    Importance Current treatments for cystoid macular edema in retinitis pigmentosa are not always effective, may lead to adverse side effects, and may not restore loss of visual acuity. The present research lays the rationale for evaluating whether an iodine supplement could reduce cystoid macular edema in retinitis pigmentosa. Objective To determine whether central foveal thickness in the presence of cystoid macular edema is related to dietary iodine intake inferred from urinary iodine concentration in non-smoking adults with retinitis pigmentosa. Design Cross-sectional study. Setting Institutional referral center. Participants Non-smoking adult patients with retinitis pigmentosa (n = 212, ages 18 to 69 years) with a visual acuity ≥ 20/200 in at least one eye. Main outcome measure The relationship of log central foveal thickness measured by optical coherence tomography to urinary iodine concentration measured from multiple spot samples and represented as a 3-level classification variable (< 100 μg/L, 100 μg/L - 199 μg/L, and ≥ 200 μg/L), assigning greater weight to patients with more reliable urinary iodine concentration estimates. Results Analyses were limited to 199 patients after excluding 11 patients who failed to return urine samples for measuring urinary iodine concentration and 2 outliers for urinary iodine concentration. Thirty-six percent of these patients had cystoid macular edema in one or both eyes. Although log central foveal thickness was inversely related to urinary iodine concentration based on all patients (p = 0.02), regression of log central foveal thickness on urinary iodine concentration separately for patients with and without cystoid macular edema showed a strong inverse significant relationship for the former group (p < 0.001) and no significant relationship for the latter group as tested (p = 0.66). In contrast, we found no significant association between cystoid macular edema prevalence and urinary iodine concentration based on the

  1. Contrast visual acuity in patients with retinitis pigmentosa assessed by a contrast sensitivity tester

    PubMed Central

    Oishi, Maho; Nakamura, Hajime; Hangai, Masanori; Oishi, Akio; Otani, Atsushi; Yoshimura, Nagahisa

    2012-01-01

    Purpose: To assess contrast visual acuity (CVA) in patients with retinitis pigmentosa (RP) and compare the result with standard visual acuity (VA), retinal thickness, status of inner segment/outer segment junction, and central visual field. Materials and Methods: Thirty-nine eyes of 39 patients with RP and 39 eyes of 39 healthy individuals were studied. To see the difference in CVA between RP patients and normal controls, only subjects with standard VA of 1.0 (20/20) or better were included. This was a cross-sectional study. CVA in various light conditions was measured with CAT-2000 and was compared between patients and controls. CVA of patients was further analyzed for association with other parameters including foveal retinal thickness, outer nuclear layer thickness, the status of inner segment/outer segment junction measured with optical coherence tomography (OCT), and visual field mean deviation (MD) measured with Humphrey field analyzer 10-2 program. Results: CVA impairment was evident in RP patients compared to controls (P < 0.01, in all measurement conditions). Multivariate analysis showed association of logarithm of the minimum angle of resolution (logMAR) with CVAs in several conditions. None of the OCT measurements was associated with CVA. When patients were divided into three groups based on MD, the most advanced group (MD worse than or equal to –20 dB) showed impairment of mesopic CVA (P < 0.05, under mesopic condition of 100% without glare, with glare, and 25% without glare). Conclusion: CVA impairment was confirmed in RP patients, especially in advanced cases. CVA measured with CAT-2000 may be a useful tool for assessing foveal function in RP patients. PMID:23202395

  2. Pattern ERG correlates of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity.

    PubMed

    Robson, Anthony G; El-Amir, Ahmed; Bailey, Claire; Egan, Catherine A; Fitzke, Frederick W; Webster, Andrew R; Bird, Alan C; Holder, Graham E

    2003-08-01

    To examine the functional significance of central abnormalities present in fundus autofluorescence (AF) images in patients with rod-cone dystrophy and good visual acuity. Thirty patients were selected according to three criteria: a clinical diagnosis of retinitis pigmentosa (RP) confirmed with International Society for Clinical Electrophysiology of Vision (ISCEV) standard ERGs, a parafoveal ring of increased high density on fundus AF imaging, and a visual acuity of 20/30 or better. Macular function was assessed with pattern electroretinography (PERG) to checkerboard stimuli of different field sizes. Fundus AF imaging was performed with a confocal scanning laser ophthalmoscope. The radius of the parafoveal ring of high density varied between 1.5 degrees and 9 degrees. The PERG P50 amplitude correlated highly with the radius of the ring of increased autofluorescence (r = 0.80, P < 0.0005, n = 30). PERGs to smaller circular field sizes were present, but increasing field size to beyond that of the high-density autofluorescence ring did not produce further increases in P50 amplitude. There was a high correlation between the minimum stimulus size required to elicit a maximum-amplitude PERG and the radius of the ring (r = 0.87). The high correlation between AF imaging and PERG, an established technique in the assessment of central retinal function, demonstrates the likelihood that autofluorescence abnormalities have functional significance and may therefore be a valuable additional parameter in the monitoring of these patients.

  3. Microarray-based mutation detection and phenotypic characterization in Korean patients with retinitis pigmentosa

    PubMed Central

    Kim, Cinoo; Kim, Kwang Joong; Bok, Jeong; Lee, Eun-Ju; Kim, Dong-Joon; Oh, Ji Hee; Park, Sung Pyo; Shin, Joo Young; Lee, Jong-Young

    2012-01-01

    Purpose To evaluate microarray-based genotyping technology for the detection of mutations responsible for retinitis pigmentosa (RP) and to perform phenotypic characterization of patients with pathogenic mutations. Methods DNA from 336 patients with RP and 360 controls was analyzed using the GoldenGate assay with microbeads containing 95 previously reported disease-associated mutations from 28 RP genes. Mutations identified by microarray-based genotyping were confirmed by direct sequencing. Segregation analysis and phenotypic characterization were performed in patients with mutations. The disease severity was assessed by visual acuity, electroretinography, optical coherence tomography, and kinetic perimetry. Results Ten RP-related mutations of five RP genes (PRP3 pre-mRNA processing factor 3 homolog [PRPF3], rhodopsin [RHO], phosphodiesterase 6B [PDE6B], peripherin 2 [PRPH2], and retinitis pigmentosa 1 [RP1]) were identified in 26 of the 336 patients (7.7%) and in six of the 360 controls (1.7%). The p.H557Y mutation in PDE6B, which was homozygous in four patients and heterozygous in nine patients, was the most frequent mutation (2.5%). Mutation segregation was assessed in four families. Among the patients with missense mutations, the most severe phenotype occurred in patients with p.D984G in RP1; less severe phenotypes occurred in patients with p.R135W in RHO; a relatively moderate phenotype occurred in patients with p.T494M in PRPF3, p.H557Y in PDE6B, or p.W316G in PRPH2; and a mild phenotype was seen in a patient with p.D190N in RHO. Conclusions The results reveal that the GoldenGate assay may not be an efficient method for molecular diagnosis in RP patients with rare mutations, although it has proven to be reliable and efficient for high-throughput genotyping of single-nucleotide polymorphisms. The clinical features varied according to the mutations. Continuous effort to identify novel RP genes and mutations in a population is needed to improve the efficiency and

  4. Unique characteristics of two types of retinitis pigmentosa patients with different rod sensitivities.

    PubMed

    Takahashi, Hiroaki; Miyake, Yozo; Horiguchi, Masayuki; Tomida, Naoki; Takakuwa, Hideo

    2005-01-01

    To determine the psychophysical differences between two types of retinitis pigmentosa (RP) patients with different rod sensitivities. Thirty-five RP patients with a visual acuity of > or =0.7 or better were classified by cone-rod perimetry into type 1, those with undetectable rod sensitivity, and type 2, those with measurable rod sensitivity. Their symptoms, age at onset of symptoms, cone and rod sensitivity, and full-field electroretinograms (ERGs) were compared. The age when the symptoms of night blindness were first noticed was 13.1 +/- 3.3 years (mean +/- SD) for type 1 and 34.5 +/- 14.4 years for type 2 patients (P = 0.0001). One of nine type 1 patients (11%) and 10 of 26 type 2 patients (38%) did not have any symptoms of night blindness. The average rod sensitivity within the central 10 degrees was 43.7 +/- 12.0 dB for type 2 patients with night blindness, and 54.8 +/- 6.4 dB for type 2 patients without night blindness (P = 0.014). One of nine (11%) type 1 patients and 9 of 23 (39%) type 2 patients had recordable ERGs (P = 0.13). These findings indicate that the two types of RP patients, distinguished by their rod sensitivity, have different psychophysical characteristics of the visual system. The course of the disease process and the long-term prognosis for these two types of patients are different.

  5. Molecular analysis of the ABCA4 gene in Turkish patients with Stargardt disease and retinitis pigmentosa.

    PubMed

    Ozgül, Riza Köksal; Durukan, Hakan; Turan, Ayse; Oner, Cihan; Ogüs, Ay; Farber, Debora B

    2004-05-01

    The clinical importance of sequence variations in the ABCA4 gene has been extensively discussed during the last decade. Mutations in the ABCA4 gene are involved in several forms of inherited retinal degenerations. We screened all 50 exons of the ABCA4 gene in a cohort of 5 Stargardt Disease (STGD) and 35 autosomal recessive retinitis pigmentosa (arRP) patients of Turkish descent to assess the nature of ABCA4 mutant alleles in this population. Our results revealed the presence of three novel mutations: c.160T>G (p.C54G), c.2486C>T (p.T829M), and c.973-6C>A; two mutations previously reported, c.634C>T (p.R212C) and c.4253+4C>T, and several polymorphic changes in the ABCA4 gene among Turkish patients affected with Stargardt and arRP. To our knowledge this report represents the first published study of ABCA4 mutations in the Turkish population resulting in STGD. Copyright 2004 Wiley-Liss, Inc.

  6. Mutation Spectrum of EYS in Spanish Patients with Autosomal Recessive Retinitis Pigmentosa

    PubMed Central

    Barragán, Isabel; Borrego, Salud; Pieras, Juan Ignacio; Pozo, María González-del; Santoyo, Javier; Ayuso, Carmen; Baiget, Montserrat; Millan, José M; Mena, Marcela; El-Aziz, Mai M Abd; Audo, Isabelle; Zeitz, Christina; Littink, Karin W; Dopazo, Joaquín; Bhattacharya, Shomi S; Antiñolo, Guillermo

    2010-01-01

    Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterised ultimately by the loss of photoreceptor cells. We have recently identified a new gene (EYS) encoding an ortholog of Drosophila spacemaker (spam) as a commonly mutated gene in autosomal recessive RP. In the present study, we report the identification of 73 sequence variations in EYS, of which 28 are novel. Of these, 42.9% (12/28) are very likely pathogenic, 17.9% (5/28) are possibly pathogenic, whereas 39.3% (11/28) are SNPs. In addition, we have detected 3 pathogenic changes previously reported in other populations. We are also presenting the characterisation of EYS homologues in different species, and a detailed analysis of the EYS domains, with the identification of an interesting novel feature: a putative coiled-coil domain. Majority of the mutations in the arRP patients have been found within the domain structures of EYS. The minimum observed prevalence of distinct EYS mutations in our group of patients is of 15.9% (15/94), confirming a major involvement of EYS in the pathogenesis of arRP in the Spanish population. Along with the detection of three recurrent mutations in Caucasian population, our hypothesis of EYS being the first prevalent gene in arRP has been reinforced in the present study. © 2010 Wiley-Liss, Inc. PMID:21069908

  7. Improving graph-based OCT segmentation for severe pathology in retinitis pigmentosa patients

    NASA Astrophysics Data System (ADS)

    Lang, Andrew; Carass, Aaron; Bittner, Ava K.; Ying, Howard S.; Prince, Jerry L.

    2017-03-01

    Three dimensional segmentation of macular optical coherence tomography (OCT) data of subjects with retinitis pigmentosa (RP) is a challenging problem due to the disappearance of the photoreceptor layers, which causes algorithms developed for segmentation of healthy data to perform poorly on RP patients. In this work, we present enhancements to a previously developed graph-based OCT segmentation pipeline to enable processing of RP data. The algorithm segments eight retinal layers in RP data by relaxing constraints on the thickness and smoothness of each layer learned from healthy data. Following from prior work, a random forest classifier is first trained on the RP data to estimate boundary probabilities, which are used by a graph search algorithm to find the optimal set of nine surfaces that fit the data. Due to the intensity disparity between normal layers of healthy controls and layers in various stages of degeneration in RP patients, an additional intensity normalization step is introduced. Leave-one-out validation on data acquired from nine subjects showed an average overall boundary error of 4.22 μm as compared to 6.02 μm using the original algorithm.

  8. The artificial silicon retina in retinitis pigmentosa patients (an American Ophthalmological Association thesis).

    PubMed

    Chow, Alan Y; Bittner, Ava K; Pardue, Machelle T

    2010-12-01

    In a published pilot study, a light-activated microphotodiode-array chip, the artificial silicon retina (ASR), was implanted subretinally in 6 retinitis pigmentosa (RP) patients for up to 18 months. The ASR electrically induced retinal neurotrophic rescue of visual acuity, contrast, and color perception and raised several questions: (1) Would neurotrophic effects develop and persist in additionally implanted RP patients? (2) Could vision in these patients be reliably assessed? (3) Would the ASR be tolerated and function for extended periods? Four additional RP patients were implanted and observed along with the 6 pilot patients. Of the 10 patients, 6 had vision levels that allowed for more standardized testing and were followed up for 7+ years utilizing ETDRS charts and a 4-alternative forced choice (AFC) Chow grating acuity test (CGAT). A 10-AFC Chow color test (CCT) extended the range of color vision testing. Histologic examination of the eyes of one patient, who died of an unrelated event, was performed. The ASR was well tolerated, and improvement and/or slowing of vision loss occurred in all 6 patients. CGAT extended low vision acuity testing by logMAR 0.6. CCT expanded the range of color vision testing and correlated well with PV-16 (r = 0.77). An ASR recovered from a patient 5 years after implantation showed minor disruption and excellent electrical function. ASR-implanted RP patients experienced prolonged neurotrophic rescue of vision. CGAT and CCT extended the range of acuity and color vision testing in low vision patients. ASR implantation may improve and prolong vision in RP patients.

  9. The Artificial Silicon Retina in Retinitis Pigmentosa Patients (An American Ophthalmological Association Thesis)

    PubMed Central

    Chow, Alan Y.; Bittner, Ava K.; Pardue, Machelle T.

    2010-01-01

    Purpose: In a published pilot study, a light-activated microphotodiode-array chip, the artificial silicon retina (ASR), was implanted subretinally in 6 retinitis pigmentosa (RP) patients for up to 18 months. The ASR electrically induced retinal neurotrophic rescue of visual acuity, contrast, and color perception and raised several questions: (1) Would neurotrophic effects develop and persist in additionally implanted RP patients? (2) Could vision in these patients be reliably assessed? (3) Would the ASR be tolerated and function for extended periods? Methods: Four additional RP patients were implanted and observed along with the 6 pilot patients. Of the 10 patients, 6 had vision levels that allowed for more standardized testing and were followed up for 7+ years utilizing ETDRS charts and a 4-alternative forced choice (AFC) Chow grating acuity test (CGAT). A 10-AFC Chow color test (CCT) extended the range of color vision testing. Histologic examination of the eyes of one patient, who died of an unrelated event, was performed. Results: The ASR was well tolerated, and improvement and/or slowing of vision loss occurred in all 6 patients. CGAT extended low vision acuity testing by logMAR 0.6. CCT expanded the range of color vision testing and correlated well with PV-16 (r = 0.77). An ASR recovered from a patient 5 years after implantation showed minor disruption and excellent electrical function. Conclusion: ASR-implanted RP patients experienced prolonged neurotrophic rescue of vision. CGAT and CCT extended the range of acuity and color vision testing in low vision patients. ASR implantation may improve and prolong vision in RP patients. PMID:21212852

  10. Use of Hydrogen as a Novel Therapeutic Strategy Against Photoreceptor Degeneration in Retinitis Pigmentosa Patients.

    PubMed

    Tao, Ye; Geng, Lei; Wang, Liqiang; Xu, Weiwei; Qin, Limin; Peng, Guanghua; Huang, Yi Fei; Yang, Ji xue

    2016-03-08

    Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterized by progressive photoreceptor apoptosis. Reactive oxygen species (ROS) have been recognized as critical initiators of the photoreceptor apoptosis in RP. Photoreceptor survival in RP mutants will not only require the inhibition of effectors of apoptotic machinery, but also the elimination of the initiating upstream signals, such as ROS. These cytotoxic ROS should be neutralized by the antioxidant defense system, otherwise they would interact with the macromolecules essential for photoreceptor survival. Hydrogen is a promising gaseous agent that has come to the forefront of therapeutic research over the last few years. It has been verified that hydrogen is capable of neutralizing the cytotoxic ROS selectively, rectifying abnormities in the apoptotic cascades, and attenuating the related inflammatory response. Hydrogen is so mild that it does not disturb the metabolic oxidation-reduction reactions or disrupt the physiologic ROS involved in cell signaling. Based on these findings, we hypothesize that hydrogen might be an effective therapeutic agent to slow or prevent photoreceptor degeneration in RP retinas. It is a logical step to test hydrogen for therapeutic use in multiple RP animal models, and ultimately in human RP patients.

  11. Mutation Screening of Multiple Genes in Spanish Patients with Autosomal Recessive Retinitis Pigmentosa by Targeted Resequencing

    PubMed Central

    González-del Pozo, María; Borrego, Salud; Barragán, Isabel; Pieras, Juan I.; Santoyo, Javier; Matamala, Nerea; Naranjo, Belén; Dopazo, Joaquín; Antiñolo, Guillermo

    2011-01-01

    Retinitis Pigmentosa (RP) is a heterogeneous group of inherited retinal dystrophies characterised ultimately by the loss of photoreceptor cells. RP is the leading cause of visual loss in individuals younger than 60 years, with a prevalence of about 1 in 4000. The molecular genetic diagnosis of autosomal recessive RP (arRP) is challenging due to the large genetic and clinical heterogeneity. Traditional methods for sequencing arRP genes are often laborious and not easily available and a screening technique that enables the rapid detection of the genetic cause would be very helpful in the clinical practice. The goal of this study was to develop and apply microarray-based resequencing technology capable of detecting both known and novel mutations on a single high-throughput platform. Hence, the coding regions and exon/intron boundaries of 16 arRP genes were resequenced using microarrays in 102 Spanish patients with clinical diagnosis of arRP. All the detected variations were confirmed by direct sequencing and potential pathogenicity was assessed by functional predictions and frequency in controls. For validation purposes 4 positive controls for variants consisting of previously identified changes were hybridized on the array. As a result of the screening, we detected 44 variants, of which 15 are very likely pathogenic detected in 14 arRP families (14%). Finally, the design of this array can easily be transformed in an equivalent diagnostic system based on targeted enrichment followed by next generation sequencing. PMID:22164218

  12. Whole exome sequencing in Thai patients with retinitis pigmentosa reveals novel mutations in six genes.

    PubMed

    Jinda, Worapoj; Taylor, Todd D; Suzuki, Yutaka; Thongnoppakhun, Wanna; Limwongse, Chanin; Lertrit, Patcharee; Suriyaphol, Prapat; Trinavarat, Adisak; Atchaneeyasakul, La-ongsri

    2014-04-07

    To identify disease-causing mutations and describe genotype-phenotype correlations in Thai patients with nonsyndromic retinitis pigmentosa (RP). Whole exome sequencing was performed in 20 unrelated patients. Eighty-six genes associated with RP, Leber congenital amaurosis, and cone-rod dystrophy were analyzed for variant detection. Seventeen variants (13 novel and 4 known) in 13 genes were identified in 11 patients. These variants include 10 missense substitutions, 2 nonsense mutations, 3 deletions, 1 insertion, and 1 splice site change. Nine patients with identified inheritance patterns carried a total of 10 potentially pathogenic mutations located in genes CRB1, C8orf37, EYS, PROM1, RP2, and USH2A. Three of the nine patients also demonstrated additional heterozygous variants in genes ABCA4, GUCY2D, RD3, ROM1, and TULP1. In addition, two patients carried variants of uncertain significance in genes FSCN2 and NR2E3. The RP phenotypes of our patients were consistent with previous reports. This is the first report of mutations in Thai RP patients. These findings are useful for genotype-phenotype comparisons among different ethnic groups.

  13. Correlation of SD-OCT findings and visual function in patients with retinitis pigmentosa.

    PubMed

    Battaglia Parodi, Maurizio; La Spina, Carlo; Triolo, Giacinto; Riccieri, Fulvio; Pierro, Luisa; Gagliardi, Marco; Bandello, Francesco

    2016-07-01

    To describe the morphological macular changes detected by spectral domain optical coherence tomography (SD-OCT) in eyes with retinitis pigmentosa (RP) and to analyze their correlation with the visual function. Twenty-two patients (44 eyes) patients affected by RP were recruited. The following structures were evaluated on SD-OCT: outer plexiform layer (OPL), outer nuclear layer (ONL), external limiting membrane (ELM), photoreceptor inner/outer segment (IS/OS) junction, photoreceptor outer segment/retinal pigmented epithelium (OS/RPE) junction, inner limiting membrane thickening (ILMT), ganglion cell complex (GCC), and cystoid macular edema (CME). The relation between each SD-OCT finding and BCVA was evaluated at uni- and multivariate analysis. Mean age and mean best-corrected visual acuity (BCVA) were 51 ± 17.5 years and 0.4 ± 0.5 LogMAR, respectively. Univariate linear regression model revealed a correlation between BCVA and the absence of ELM, IS/OS, ONL, and OS/RPE layers (R (2) values were, respectively, 0.51, 0.57, 0.48, and 0.68, with p values all <0.0001). At multivariate regression analysis, the absence of OS/RPE and ELM layers remained the only variables independently associated with a decrease of BCVA (R (2) = 0.85, t = 3.49, p = 0.0014). Data show that in patients afflicted with RP, ELM and OS/RPE layers are independently associated with BCVA on multivariate regression analysis. These results highlight the key-role of external retinal layers in determining the visual function impairment attributable to RP.

  14. Spectral domain optical coherence tomography findings in patients with retinitis pigmentosa.

    PubMed

    Triolo, Giacinto; Pierro, Luisa; Parodi, Maurizio Battaglia; De Benedetto, Umberto; Gagliardi, Marco; Manitto, Maria Pia; Bandello, Francesco

    2013-01-01

    To report the morphological macular findings detected by spectral domain optical coherence tomography (SD-OCT) and to determine their prevalence in patients with retinitis pigmentosa (RP). SD-OCT scans of 176 eyes from 90 patients affected by RP were reviewed. A careful evaluation was carried out on photoreceptor inner/outer segment (IS/OS) junction, external limiting membrane (ELM), inner limiting membrane thickening (ILMT), epiretinal membranes (ERMs), retinal micropseudocysts (MPCs), cystoid macular edema (CME), macular holes (MHs) and choroidal neovascularization (CNV). The photoreceptor IS/OS junction was absent in the foveal region of 24 eyes (13.6%) and disrupted in 84 eyes (47.7%). The ELM was absent in 24 eyes (13.6%), whereas the ILMT was found in 118 eyes (67%). The presence of an ERM was detected in 48 eyes (27.3%). Some sort of vitreomacular alteration (ILMT and/or ERM) was identifiable in a total of 94.3% of eyes with RP. The presence of MPCs was detected in 32 eyes (18.2%). An evident CME was found in 22 eyes (12.5%). We also found MHs in 8 eyes (4.5%) and CNV in 3 eyes (1.7%). Our data indicate that RP is associated with alterations of many retinal layers. In particular, the vitreoretinal interface is affected in 94% of patients, and MPC can be identified in 18% of eyes. SD-OCT may contribute to the understanding of the pathophysiological mechanism involved in RP. Copyright © 2013 S. Karger AG, Basel.

  15. [Long-term follow-up of a case of unilateral retinitis pigmentosa].

    PubMed

    Kato, Kumiko; Miyake, Yozo; Matsubara, Hisashi; Uji, Yukitaka

    2012-11-01

    Unilateral retinitis pigmentosa is a retinal dystrophy affecting only one eye, the fellow eye being affected neither functionally nor in fundus appearance. There are relatively few cases of unilateral retinitis pigmentosa being followed for more than 5 years. An 18-year-old woman complaining of blurred vision of left eye was found to have left visual field concentric contraction. Because the right eye was unaffected electrofunctionally and in fundus appearance, there was a suspicion of unilateral retinitis pigmentosa. We tracked her for 8 years and, because the right eye remained unaffected, we diagnosed unilateral retinitis pigmentosa of left eye. We report a case of unilateral retinitis pigmentosa. It is reported that the healthy fellow eye of patients with unilateral retinitis pigmentosa developed bilateral retinitis pigmentosa after 10 years, consequently, this case needs further follow-up.

  16. Two specific mutations are prevalent causes of recessive retinitis pigmentosa in North American patients of Jewish ancestry.

    PubMed

    Venturini, Giulia; Koskiniemi-Kuendig, Hanna; Harper, Shyana; Berson, Eliot L; Rivolta, Carlo

    2015-04-01

    Retinitis pigmentosa is a Mendelian disease with a very elevated genetic heterogeneity. Most mutations are responsible for less than 1% of cases, making molecular diagnosis a multigene screening procedure. In this study, we assessed whether direct testing of specific alleles could be a valuable screening approach in cases characterized by prevalent founder mutations. We screened 275 North American patients with recessive/isolate retinitis pigmentosa for two mutations: an Alu insertion in the MAK gene and the p.Lys42Glu missense in the DHDDS gene. All patients were unrelated; 35 reported Jewish ancestry and the remainder reported mixed ethnicity. We identified the MAK and DHDDS mutations homozygously in only 2.1% and 0.8%, respectively, of patients of mixed ethnicity, but in 25.7% and 8.6%, respectively, of cases reporting Jewish ancestry. Haplotype analyses revealed that inheritance of the MAK mutation was attributable to a founder effect. In contrast to most mutations associated with retinitis pigmentosa-which are, in general, extremely rare-the two alleles investigated here cause disease in approximately one-third of North American patients reporting Jewish ancestry. Therefore, their screening constitutes an alternative procedure to large-scale tests for patients belonging to this ethnic group, especially in time-sensitive situations.

  17. Retrospective longitudinal study of visual acuity change in patients with retinitis pigmentosa.

    PubMed

    Flynn, M F; Fishman, G A; Anderson, R J; Roberts, D K

    2001-01-01

    To determine the extent that clinically evident macular lesions in patients with retinitis pigmentosa (RP) help to establish their prognosis for visual acuity (VA) retention. The records of 182 patients with RP were reviewed. The macular lesion status at the initial examination was determined to be no lesion, a bull's-eye atrophic lesion, or a geographic atrophic lesion. Multiple linear regression analysis was used to evaluate the relationship of initial VA, macular lesion type, and RP genetic subtype to predict the VA change per 5-year period. The regression effect of lesion type on the VA change was statistically significant (P < 0.0001). Patients with no macular lesion had a predicted 5-year change of less than 1 line, whereas those with either a bull's-eye or geographic atrophic lesion had a predicted 5-year change of three to four lines. The 5-year changes were not related to a patient's age or level of VA at initial presentation, when controlling for type of macular lesion. By examining longitudinal data, the authors found that the presence or absence of a macular lesion at the patient's initial visit was an important determinant of VA loss in this cohort of patients with RP. These findings are of value when counseling patients with RP regarding their prognosis for preservation of VA.

  18. Structural analysis of retinal photoreceptor ellipsoid zone and postreceptor retinal layer associated with visual acuity in patients with retinitis pigmentosa by ganglion cell analysis combined with OCT imaging

    PubMed Central

    Liu, Guodong; Li, Hui; Liu, Xiaoqiang; Xu, Ding; Wang, Fang

    2016-01-01

    Abstract The aim of this study was to examine changes in photoreceptor ellipsoid zone (EZ) and postreceptor retinal layer in retinitis pigmentosa (RP) patients by ganglion cell analysis (GCA) combined with optical coherence tomography (OCT) imaging to evaluate the structure–function relationships between retinal layer changes and best corrected visual acuity (BCVA). Sixty-eight eyes of 35 patients with RP and 65 eyes of 35 normal controls were analyzed in the study. The average length of EZ was 911.1 ± 208.8 μm in RP patients, which was shortened with the progression of the disease on the OCT images. The average ganglion cell–inner plexiform layer thickness (GCIPLT) was 54.7 ± 18.9 μm in RP patients, while in normal controls it was 85.6 ± 6.8 μm. The GCIPLT in all quarters became significantly thinner along with outer retinal thinning. There was a significantly positive correlation between BCVA and EZ (r = −0.7622, P < 0.001) and GCIPLT (r = −0.452, P < 0.001). Therefore, we assess the retinal layer changes from a new perspective in RP patients, which suggests that EZ and GCIPLT obtained by GCA combined with OCT imaging are the direct and valid indicators to diagnosis and predict the pathological process of RP. PMID:28033301

  19. Dark-Adapted Chromatic Perimetry for Measuring Rod Visual Fields in Patients with Retinitis Pigmentosa.

    PubMed

    Bennett, Lea D; Klein, Martin; Locke, Kirsten G; Kiser, Kelly; Birch, David G

    2017-07-01

    Although rod photoreceptors are initially affected in retinitis pigmentosa (RP), the full-field of rod vision is not routinely characterized due to the unavailability of commercial devices detecting rod sensitivity. The purpose of this study was to quantify rod-mediated vision in the peripheral field from patients with RP using a new commercially available perimeter. Participants had one eye dilated and dark-adapted for 45 minutes. A dark-adapted chromatic (DAC) perimeter tested 80 loci 144° horizontally and 72° vertically with cyan stimuli. The number of rod-mediated loci (RML) were analyzed based on normal cone sensitivity (method 1) and associated with full-field electroretinography (ERG) responses by Pearson's r correlation and linear regression. In a second cohort of patients with RP, RML were identified by two-color perimetry (cyan and red; method 2). The two methods for ascribing rod function were compared by Bland-Altman analysis. Method 1 RML were correlated with responses to the 0.01 cd.s/m(2) flash (P < 0.001), while total sensitivity to the cyan stimulus showed correlation with responses to the 3.0 cd.s/m(2) flash (P < 0.0001). Method 2 detected a mean of 10 additional RML compared to method 1. Scotopic fields measured with the DAC detected rod sensitivity across the full visual field, even in some patients who had nondetectable rod ERGs. Two-color perimetry is warranted when sensitivity to the cyan stimulus is reduced to ≤20 dB to get a true estimation of rod function. Many genetic forms of retinitis pigmentosa (RP) are caused by mutations in rod-specific genes. However, treatment trials for patients with RP have relied primarily on photopic (cone-mediated) tests as outcome measures because there are a limited number of available testing methods designed to evaluate rod function. Thus, efficient methods for quantifying rod-mediated vision are needed for the rapidly increasing numbers of clinical trials.

  20. Is There Excess Oxidative Stress and Damage in Eyes of Patients with Retinitis Pigmentosa?

    PubMed Central

    Strauss, Rupert W.; Lu, Lili; Hafiz, Gulnar; Wolfson, Yulia; Shah, Syed M.; Sophie, Raafay; Mir, Tahreem A.; Scholl, Hendrik P.

    2015-01-01

    Abstract Retinitis pigmentosa (RP) is a group of diseases in which a mutation in one of the large variety of genes causes death of rod photoreceptors. After rods die, cone photoreceptors gradually die resulting in constriction of visual fields and eventual blindness in many patients. Studies in animal models of RP have demonstrated that oxidative damage is a major contributor to cone cell death. In this study, we extended those findings to patients with RP, because compared to control patients, those with RP showed significant reduction in the reduced to oxidized glutathione (GSH/GSSG) ratio in aqueous humor and a significant increase in aqueous protein carbonyl content. In contrast, there was no significant decrease in the serum GSH/GSSG ratio or increase in carbonyl content of serum proteins. These data indicate that patients with RP have ocular oxidative stress and damage in the absence of manifestations of systemic oxidative stress and/or damage indicating that demonstrations of oxidative damage-induced cone cell death in animal models of RP may translate to human RP. These observations lead to the hypothesis that potent antioxidants will promote cone survival and function in patients with RP and that the aqueous GSH/GSSG ratio and carbonyl content on proteins may provide useful biomarkers. Antioxid. Redox Signal. 23, 643–648. PMID:25820114

  1. Anterior lens epithelium in cataract patients with retinitis pigmentosa - scanning and transmission electron microscopy study.

    PubMed

    Andjelic, Sofija; Drašlar, Kazimir; Hvala, Anastazija; Hawlina, Marko

    2017-05-01

    In retinitis pigmentosa (RP) patients, relatively minor lens opacity in central part of posterior pole of the lens may cause disproportionate functional symptoms requiring cataract operation. To investigate the possible structural reasons for this opacity development, we studied the structure of the lens epithelium of patients with RP. The anterior lens capsule (aLC: basement membrane and associated lens epithelial cells, LECs) was obtained from cataract surgery and prepared for scanning and transmission electron microscopy (SEM and TEM). Both SEM and TEM show a number of abnormal features in the anterior lens epithelium of cataract patients with RP. The abnormalities appear mainly as holes, thinning and degradation of the epithelium, with the dimensions from <1 μm to more than 50 μm. Other types of holes in size up to 20 μm were seen that may be formed by gradual stretching of the lens epithelium. Another type of abnormalities was cracks that were seen between adjacent LECs, with dimensions 0.1-2 μm × up to 10 μm. Abnormal structural features were observed in the anterior lens epithelium that may cause water influx into the lens. This may lead to clouding along the water clefts leading towards the posterior pole in the RP cataractous lens. We suggest that the lens epithelium has a role in the development of the cataract in patients with RP. © 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  2. Disease progression in patients with dominant retinitis pigmentosa and rhodopsin mutations.

    PubMed

    Berson, Eliot L; Rosner, Bernard; Weigel-DiFranco, Carol; Dryja, Thaddeus P; Sandberg, Michael A

    2002-09-01

    To measure the rate of progression of retinal degeneration in patients with retinitis pigmentosa due to dominant rhodopsin mutations and to determine whether the rate of progression correlates with the location of the altered amino acid in the rhodopsin molecule. Change in ocular function was observed for an average of 8.7 years in 140 patients. After censoring data to eliminate "ceiling" and "floor" effects, longitudinal rates of change were compared, after weighting by follow-up time and number of visits, with rates inferred from cross-sectional analyses of the data from baseline visits. Mean rates of change were compared among groups of patients with mutations affecting the globule, plug, or C-terminal region of the protein after adjusting for age, gender, and baseline function. Mean annual exponential rates of decline were 1.8% for visual acuity, 2.6% for visual field area, and 8.7% for ERG amplitude. The rates of visual acuity and ERG amplitude decline were significantly faster, and the rate of visual field area decline was significantly slower, than those inferred from baseline visits. Rates of acuity loss did not vary significantly with the region affected by the mutation. In contrast, the mean annual rate of field loss in the C terminus group (7.4%) was significantly faster than that in the globule (1.7%) or plug (1.1%) group. The mean annual rate of ERG decline was also significantly faster in the C terminus group (13.5%) than in the globule (8.5%) or plug (3.7%) groups and significantly faster in the globule group than in the plug group. Rates of decline in visual function for groups of patients with rhodopsin mutations cannot be accurately inferred from cross-sectional analyses of baseline visits. Average rates of decline of visual field area and ERG amplitude are fastest in patients with mutations affecting the C-terminal region.

  3. Retinal Remodeling in Human Retinitis Pigmentosa

    PubMed Central

    Jones, B.W.; Pfeiffer, R.L.; Ferrell, W. D.; Watt, C.B.; Marmor, M.; Marc, R.E.

    2016-01-01

    Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies. PMID:27020758

  4. Retinal remodeling in human retinitis pigmentosa.

    PubMed

    Jones, B W; Pfeiffer, R L; Ferrell, W D; Watt, C B; Marmor, M; Marc, R E

    2016-09-01

    Retinitis Pigmentosa (RP) in the human is a progressive, currently irreversible neural degenerative disease usually caused by gene defects that disrupt the function or architecture of the photoreceptors. While RP can initially be a disease of photoreceptors, there is increasing evidence that the inner retina becomes progressively disorganized as the outer retina degenerates. These alterations have been extensively described in animal models, but remodeling in humans has not been as well characterized. This study, using computational molecular phenotyping (CMP) seeks to advance our understanding of the retinal remodeling process in humans. We describe cone mediated preservation of overall topology, retinal reprogramming in the earliest stages of the disease in retinal bipolar cells, and alterations in both small molecule and protein signatures of neurons and glia. Furthermore, while Müller glia appear to be some of the last cells left in the degenerate retina, they are also one of the first cell classes in the neural retina to respond to stress which may reveal mechanisms related to remodeling and cell death in other retinal cell classes. Also fundamentally important is the finding that retinal network topologies are altered. Our results suggest interventions that presume substantial preservation of the neural retina will likely fail in late stages of the disease. Even early intervention offers no guarantee that the interventions will be immune to progressive remodeling. Fundamental work in the biology and mechanisms of disease progression are needed to support vision rescue strategies.

  5. Evaluation of the arrestin gene in patients with retinitis pigmentosa or an allied disease

    SciTech Connect

    DeStefano, D.J.; Berson, E.L.; Dryja, T.P.

    1994-09-01

    Arrestin, also called 48K protein or S-antigen, plays a role in deactivating rhodopsin, the photosensitive, seven-helix, G-protein receptor found in rod photoreceptors. In Drosophila, null mutations in arrestin genes cause a light-dependent photoreceptor degeneration. It is possible that a comparable photoreceptor degeneration in humans is caused by defects in the rod arrestin gene. In order to evaluate this possibility, we are characterizing the human arrestin locus on chromosome 2q. We screened a genomic library (5 million plaques) using an arrestin cDNA clone. Sixty-eight hybridizing clones were identified; portions of 7 clones were sequenced to determine the intron sequence flanking the exons. We are using SSCP analysis and direct genomic sequencing to screen the entire coding region, splice donor and acceptor sites, and the promoter region of the arrestin gene in 188 patients with autosomal dominant and 104 patients with autosomal recessive retinitis pigmentosa. We have already obtained flanking intron sequences necessary for SSCP analysis for 13 of 16 exons. So far, we have identified 4 silent base changes at codons 67 (TGC-to-TGT), 107 (CTG-to-CTC), 163 (GCC-to-GCT), and 288 (CTG-to-TGT), all with allele frequencies at 1% or less. Several other variant bands detected by SSCP analysis are currently being sequenced.

  6. RP2 and RPGR mutations and clinical correlations in patients with X-linked retinitis pigmentosa.

    PubMed

    Sharon, Dror; Sandberg, Michael A; Rabe, Vivian W; Stillberger, Melissa; Dryja, Thaddeus P; Berson, Eliot L

    2003-11-01

    We determined the mutation spectrum of the RP2 and RPGR genes in patients with X-linked retinitis pigmentosa (XLRP) and searched for correlations between categories of mutation and severity of disease. We screened 187 unrelated male patients for mutations, including 135 with a prior clinical diagnosis of XLRP, 11 with probable XLRP, 30 isolate cases suspected of having XLRP, and 11 with cone-rod degeneration. Mutation screening was performed by single-strand conformation analysis and by sequencing of all RP2 exons and RPGR exons 1-14, ORF15, and 15a. The refractive error, visual acuity, final dark-adapted threshold, visual field area, and 30-Hz cone electroretinogram (ERG) amplitude were measured in each patient. Among the 187 patients, we found 10 mutations in RP2, 2 of which are novel, and 80 mutations in RPGR, 41 of which are novel; 66% of the RPGR mutations were within ORF15. Among the 135 with a prior clinical diagnosis of XLRP, mutations in the RP2 and RPGR genes were found in 9 of 135 (6.7%) and 98 of 135 (72.6%), respectively, for a total of 79% of patients. Patients with RP2 mutations had, on average, lower visual acuity but similar visual field area, final dark-adapted threshold, and 30-Hz ERG amplitude compared with those with RPGR mutations. Among patients with RPGR mutations, those with ORF15 mutations had, on average, a significantly larger visual field area and a borderline larger ERG amplitude than did patients with RPGR mutations in exons 1-14. Among patients with ORF15 mutations, regression analyses showed that the final dark-adapted threshold became lower (i.e., closer to normal) and that the 30-Hz ERG amplitude increased as the length of the wild-type ORF15 amino acid sequence increased. Furthermore, as the length of the abnormal amino acid sequence following ORF15 frameshift mutations increased, the severity of disease increased.

  7. Retinitis pigmentosa and renal failure in a patient with mutations in INVS.

    PubMed

    O'Toole, John F; Otto, Edgar A; Frishberg, Yaacov; Hildebrandt, Friedhelm

    2006-07-01

    Nephronophthisis (NPHP) is an autosomal recessive disease, which is the most common genetic cause of end-stage renal disease in the first three decades of life. The disease is caused by mutations in the NPHP 1-5 genes, and is referred to as NPHP types 1-5, respectively. The association of NPHP and retinitis pigmentosa (RP) is known as Senior-Loken syndrome (SLS). The RP is associated with 10% of cases of NPHP types 1, 3 and 4, and all cases of NPHP type 5, but never in NPHP type 2, the infantile form of NPHP. The NPHP type 2 is distinguished from other types of NPHP by its early age of onset and by cystic enlargement of the kidneys. Mutational analysis of all five NPHP genes was performed by exon sequencing in a child with infantile NPHP and RP from a consanguineous kindred. A homozygous mutation was identified in exon 13 of inversin (INVS) (C2719T, R907X) in this child. This is the first report of the presence of RP in a patient with NPHP type 2 and INVS mutations. This report now extends the association of RP with NPHP to NPHP type 2.

  8. Reduced Central Retinal Artery Blood Flow Is Related to Impaired Central Visual Function in Retinitis Pigmentosa Patients.

    PubMed

    Kayser, Samantha; Vargas, Patricia; Mendelsohn, Deborah; Han, Jorge; Bi, Hua; Benavente, Alexandra; Bittner, Ava K

    2017-09-14

    We evaluated the test-retest repeatability of blood flow velocities in the retrobulbar central retinal artery (CRA) and explored whether reduced blood flow is related to the degree of visual function loss in retinitis pigmentosa (RP) patients with wide range of disease severity. We measured CRA peak systolic velocity (PSV) and end diastolic velocity (EDV) to calculate mean flow velocity (MFV) in 18 RP patients using color Doppler imaging with spectral flow Doppler (GE Logiq7 ultrasound) twice in each eye at each of two visits within a month. At each of these two visits, we measured ETDRS visual acuity (VA), quick Contrast Sensitivity Function (qCSF), Goldmann visual fields (GVF), 10-2 Humphrey visual fields (HVF), and dark-adaptation at 5° from fixation with the AdaptDx; multifocal electroretinography (mfERG) was obtained at a single visit. Mean coefficients of variation for PSV, EDV and MFV were 16.1-19.2% for within-visit measurements and 20.1-22.4% for between-visit measures. Across patients, greater visual function loss assessed with VA (p = 0.04), extinguished versus measurable amplitude in ring 1 for mfERG (p = 0.001), and cone-only versus rod function with the AdaptDx (p = 0.002) were statistically significantly correlated with reduced MFV in the CRA when included a multilevel multivariate regression model along with the qCSF and HVF results, which all together accounted for 47% of the total variance in MFV. GVF log retinal areas (V4e and III4e; p = 0.30 and p = 0.95, respectively) and measurable far peripheral vision during GVF testing (p = 0.66) were not significantly related to MFV. MFV in the CRA decreased with impaired central vision due to loss of both rod and cone function, had good test-retest repeatability, and may serve as a biomarker outcome to determine the potential physiological basis for improvements in RP clinical trials of therapies with indirect effects on blood flow to the retina.

  9. Molecular Genetics of FAM161A in North American Patients with Early-Onset Retinitis Pigmentosa

    PubMed Central

    Harper, Shyana; Weigel-DiFranco, Carol

    2014-01-01

    Retinitis pigmentosa (RP) is a hereditary disease that leads to the progressive degeneration of retinal photoreceptor cells and to blindness. It is caused by mutations in several distinct genes, including the ciliary gene FAM161A, which is associated with a recessive form of this disorder. Recent investigations have revealed that defects in FAM161A represent a rather prevalent cause of hereditary blindness in Israel and the Palestinian territories, whereas they seem to be rarely present within patients from Germany. Genetic or clinical data are currently not available for other countries. In this work, we screened a cohort of patients with recessive RP from North America to determine the frequency of FAM161A mutations in this ethnically-mixed population and to assess the phenotype of positive cases. Out of 273 unrelated patients, only 3 subjects had defects in FAM161A. A fourth positive patient, the sister of one of these index cases, was also identified following pedigree analysis. They were all homozygous for the p.T452Sfx3 mutation, which was previously reported as a founder DNA variant in the Israeli and Palestinian populations. Analysis of cultured lymphoblasts from patients revealed that mutant FAM161A transcripts were actively degraded by nonsense-mediated mRNA decay. Electroretinographic testing showed 30 Hz cone flicker responses in the range of 0.10 to 0.60 microvolts in all cases at their first visit (age 12 to 23) (lower norm  =  50 μV) and of 0.06 to 0.32 microvolts at their most recent examination (age 27 to 43), revealing an early-onset of this progressive disease. Our data indicate that mutations in FAM161A are responsible for 1% of recessive RP cases in North America, similar to the prevalence detected in Germany and unlike the data from Israel and the Palestinian territories. We also show that, at the molecular level, the disease is likely caused by FAM161A protein deficiency. PMID:24651477

  10. Retinal nerve fiber layer analysis with scanning laser polarimetry and RTVue-OCT in patients of retinitis pigmentosa.

    PubMed

    Xue, Kang; Wang, Min; Chen, Junyi; Huang, Xin; Xu, Gezhi

    2013-01-01

    To measure the thickness of the retinal nerve fiber layer (RNFL) of patients with retinitis pigmentosa (RP) and that of normal controls by scanning laser polarimetry with enhanced corneal compensation (GDxECC) and RTVue-optical coherence tomography (OCT). Fifty-two eyes of 26 patients were included. All patients underwent complete ophthalmological examinations and testing with GDxECC. Twenty-eight of 52 eyes of RP patients underwent RTVue-OCT measurements. A group of 50 eyes of 25 normal subjects (controls) was also included. GDxECC measured RNFL thickness in the peripapillary area in all subjects as well as temporal-superior-nasal-inferior-temporal (TSNIT) parameters, including TSNIT means, superior and inferior region means, TSNIT standard deviation (SD), inter-eye symmetry and nerve fiber indicator (NFI). RTVue-OCT measured the mean, superior, inferior, temporal and nasal quadrant RNFL thickness. In RP patients and controls, TSNIT means by GDxECC were, respectively, 65.00 ± 7.35 and 55.32 ± 5.20. Mean superior quadrant thicknesses were 80.56 ± 10.93 and 69.54 ± 7.45. Mean inferior thicknesses were 80.58 ± 9.34 and 69.12 ± 7.78. SDs were 27.92 ± 5.21 and 28.23 ± 4.01. Inter-eye symmetries were 0.82 ± 0.17 and 0.87 ± 0.09. NFIs were 9.74 ± 8.73 and 16.81 ± 8.13. The differences between mean TSNIT, mean superior and mean inferior quadrant thicknesses and NFIs were statistically significant (p < 0.001). In RTVue-OCT measurements, the differences between mean, superior, inferior and temporal quadrant RNFL thicknesses were statistically significant (p = 0.0322, 0.0213, 0.0387, 0.0005). The RNFL measured by GDxECC was significantly thicker in RP patients than in controls. RNFL thickness measured by RTVue-OCT was significantly greater in RP patients than in controls in the superior, inferior and temporal regions. This contribution provides information on RNFL thickness and discusses the mechanism underlying this phenomenon. Copyright © 2012 S. Karger AG

  11. Genetics Home Reference: neuropathy, ataxia, and retinitis pigmentosa

    MedlinePlus

    ... Genetics Home Health Conditions NARP neuropathy, ataxia, and retinitis pigmentosa Enable Javascript to view the expand/collapse boxes. ... Open All Close All Description Neuropathy, ataxia, and retinitis pigmentosa ( NARP ) is a condition that causes a variety ...

  12. Acanthocytosis, retinitis pigmentosa, and pallidal degeneration: a report of three patients, including the second reported case with hypoprebetalipoproteinemia (HARP syndrome).

    PubMed

    Orrell, R W; Amrolia, P J; Heald, A; Cleland, P G; Owen, J S; Morgan-Hughes, J A; Harding, A E; Marsden, C D

    1995-03-01

    We describe an example of a variant of Hallervorden-Spatz disease, characterized by hypoprebeta-lipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration (HARP syndrome), in an 18-year-old woman who presented with longstanding intellectual subnormality, night blindness, and a 2-year history of orobuccolingual dystonia causing dysarthria and dysphagia. Investigation showed acanthocytosis and hypoprebetalipoproteinemia, and electroretinograms were typical of tapetoretinal degeneration. T2-weighted MRI showed decreased signal intensity in the pallidal nuclei with central hyperintensity, constituting the "eye-of-the-tiger" sign. The patient's sister and mother have a similar lipid disorder but no retinal or neurologic disease. We also report two patients with clinical and radiologic features similar to those of the patient with HARP syndrome but who had normal lipid studies. These various combinations of components of HARP syndrome may be caused by several distinct genetic diseases or may represent variable manifestations of a contiguous gene defect.

  13. [The characteristics of retinitis pigmentosa with retinal vascular occlusion].

    PubMed

    Wang, Guang-lu; Lu, Ning; Zhang, Feng; Peng, Xiao-yan; Li, Yang; Wang, Ming-yang

    2005-05-01

    To observe clinical features of Retinitis pigmentosa with retinal vascular occlusion and its prognosis. To analyze the clinical Data in 18 cases retrospectively using fundus examination, fundus fluorescein angiography, indocyanine green angiography, electroretinogram, visually evoked potential etc. Gene screening was performed in 3 cases. the major clinical manifestations of the disease were optic atrophy, vascular attenuation to obliteration, widespread retinal pigment epithelium atrophy with depigmentation and/or fine pigment spots, total or nearly total a and b wave were extinct in the examination of electroretinogram. All this manifestations were compatible with that of typical Retinitis Pigmentosa (tapeto-retinal dystrophy). It also had its unique features, such as total or nearly total vascular obliteration, marked optic atrophy in later stage, and choroidal vessels abnormal. Gene mutation was not found in gene encoding area of RHO gene of No: 3 chromosome and of RLBPI gene of No: 15 chromosome. vision loss in this kind retinitis pigmentosa is much faster than that of typical retinitis pigmentosa. Retinitis pigmentosa with retinal vascular occlusion may belonged to a kind of tapeto-retinal dystrophy, vascular progressive obliteration was probably its associated disease.

  14. Reported effects of non-traditional treatments and complementary and alternative medicine by retinitis pigmentosa patients

    PubMed Central

    Kiser, Ava K; Dagnelie, Gislin

    2011-01-01

    Background Benefits of complementary and alternative medicine (CAM)-related interventions have been demonstrated for patients with chronic, systemic diseases in which stress, anxiety and disability are prevalent. Subjects with retinitis pigmentosa (RP) commonly indicate that they have ‘good’ and ‘bad’ vision days, stating that stress causes a decrease in vision and that vision improves when the stress is alleviated. We assessed CAM use by RP patients and its perceived effectiveness. Methods We enquired about nine CAM areas: meditation, mind-body therapies, yoga, movement therapies, energy therapies, acupuncture, massage therapy, spirituality/religion and herbal therapies/aromatherapy. Ninety-six RP patients with any level of vision completed an anonymous internet survey. Results Ninety-five per cent of respondents tried at least one of the nine CAM areas. Seventy-five per cent have used nutritional supplements, including lutein (47 per cent), bilberry (32), vitamin A palmitate (36) and docosahexaenoic acid (23 per cent). Some tried meditation (47) and yoga (31 per cent). Stress and anxiety levels were reported as improved in 93, 92 and 87 per cent of those who used yoga, meditation and mind-body therapies, respectively. Many of those who tried mind-body therapies (40) or acupuncture (50 per cent), used it with a desire to fight RP. Vision was subjectively affected in 65 per cent of acupuncture users and from 20 to 35 per cent of the users of the other CAM areas. Those who indicated that their vision was affected by at least one type of CAM (35 per cent) were statistically significantly more likely to require magnification to read (that is, they had lost more vision and RP had progressed), than those who did not believe vision was impacted (59 versus 84 per cent). Conclusions RP patients are using CAM and are experiencing some impact on vision and physical/emotional well-being. Clinicians and researchers should be aware of its use. Clinical trials with CAM

  15. Retinitis pigmentosa associated with Fuchs' heterochromic uveitis.

    PubMed

    Chowers, I; Zamir, E; Banin, E; Merin, S

    2000-06-01

    To investigate whether the combination of Fuchs' heterochromic uveitis (FHU) and retinitis pigmentosa (RP) in the same patient is coincidental or represents a true association. We have examined the frequency of FHU in 338 patients with RP and in 1984 patients who were seen in our primary care ophthalmic clinic because of reasons other than RP. Of 338 patients with RP, 4 (1.2%) had the typical findings of FHU. Three of them had Usher syndrome type II, and 1 had RP simplex. By contrast, only 1 patient in the control group had FHU (5%), and the difference in the frequency of FHU between the 2 groups was significant (P=.002, Fisher exact test). Fuchs' heterochromic uveitis is associated with RP. Since autoimmune phenomena have been previously described in patients with RP, it is conceivable that RP predisposes to the development of FHU. Arch Ophthalmol. 2000;118:800-802

  16. Low Vision Rehabilitation of Retinitis Pigmentosa. Practice Report

    ERIC Educational Resources Information Center

    Rundquist, John

    2004-01-01

    Retinitis pigmentosa is a rod-cone dystrophy, commonly genetic in nature. Approximately 60-80% of those with retinitis pigmentosa inherit it by an autosomal recessive transmission (Brilliant, 1999). There have been some reported cases with no known family history. The symptoms of retinitis pigmentosa are decreased acuity, photophobia, night…

  17. Comprehensive molecular diagnosis of 179 Leber congenital amaurosis and juvenile retinitis pigmentosa patients by targeted next generation sequencing

    PubMed Central

    Wang, Xia; Wang, Hui; Sun, Vincent; Tuan, Han-Fang; Keser, Vafa; Wang, Keqing; Ren, Huanan; Lopez, Irma; Zaneveld, Jacques E; Siddiqui, Sorath; Bowles, Stephanie; Khan, Ayesha; Salvo, Jason; Jacobson, Samuel G; Iannaccone, Alessandro; Wang, Feng; Birch, David; Heckenlively, John R; Fishman, Gerald A; Traboulsi, Elias I; Li, Yumei; Wheaton, Dianna; Koenekoop, Robert K; Chen, Rui

    2014-01-01

    Background Leber congenital amaurosis (LCA) and juvenile retinitis pigmentosa (RP) are inherited retinal diseases that cause early onset severe visual impairment. An accurate molecular diagnosis can refine the clinical diagnosis and allow gene specific treatments. Methods We developed a capture panel that enriches the exonic DNA of 163 known retinal disease genes. Using this panel, we performed targeted next generation sequencing (NGS) for a large cohort of 179 unrelated and prescreened patients with the clinical diagnosis of LCA or juvenile RP. Systematic NGS data analysis, Sanger sequencing validation, and segregation analysis were utilised to identify the pathogenic mutations. Patients were revisited to examine the potential phenotypic ambiguity at the time of initial diagnosis. Results Pathogenic mutations for 72 patients (40%) were identified, including 45 novel mutations. Of these 72 patients, 58 carried mutations in known LCA or juvenile RP genes and exhibited corresponding phenotypes, while 14 carried mutations in retinal disease genes that were not consistent with their initial clinical diagnosis. We revisited patients in the latter case and found that homozygous mutations in PRPH2 can cause LCA/juvenile RP. Guided by the molecular diagnosis, we reclassified the clinical diagnosis in two patients. Conclusions We have identified a novel gene and a large number of novel mutations that are associated with LCA/juvenile RP. Our results highlight the importance of molecular diagnosis as an integral part of clinical diagnosis. PMID:23847139

  18. Patient-specific induced pluripotent stem cells to evaluate the pathophysiology of TRNT1-associated Retinitis pigmentosa.

    PubMed

    Sharma, Tasneem P; Wiley, Luke A; Whitmore, S Scott; Anfinson, Kristin R; Cranston, Cathryn M; Oppedal, Douglas J; Daggett, Heather T; Mullins, Robert F; Tucker, Budd A; Stone, Edwin M

    2017-03-18

    Retinitis pigmentosa (RP) is a heterogeneous group of monogenic disorders characterized by progressive death of the light-sensing photoreceptor cells of the outer neural retina. We recently identified novel hypomorphic mutations in the tRNA Nucleotidyl Transferase, CCA-Adding 1 (TRNT1) gene that cause early-onset RP. To model this disease in vitro, we generated patient-specific iPSCs and iPSC-derived retinal organoids from dermal fibroblasts of patients with molecularly confirmed TRNT1-associated RP. Pluripotency was confirmed using rt-PCR, immunocytochemistry, and a TaqMan Scorecard Assay. Mutations in TRNT1 caused reduced levels of full-length TRNT1 protein and expression of a truncated smaller protein in both patient-specific iPSCs and iPSC-derived retinal organoids. Patient-specific iPSCs and iPSC-derived retinal organoids exhibited a deficit in autophagy, as evidenced by aberrant accumulation of LC3-II and elevated levels of oxidative stress. Autologous stem cell-based disease modeling will provide a platform for testing multiple avenues of treatment in patients suffering from TRNT1-associated RP.

  19. Stem cell therapy: a novel approach for vision restoration in retinitis pigmentosa.

    PubMed

    Uy, Harvey Siy; Chan, Pik Sha; Cruz, Franz Marie

    2013-01-01

    Unfortunately, at present, degenerative retinal diseases such as retinitis pigmentosa remains untreatable. Patients with these conditions suffer progressive visual decline resulting from continuing loss of photoreceptor cells and outer nuclear layers. However, stem cell therapy is a promising approach to restore visual function in eyes with degenerative retinal diseases such as retinitis pigmentosa. Animal studies have established that pluripotent stem cells when placed in the mouse retinitis pigmentosa models have the potential not only to survive, but also to differentiate, organize into and function as photoreceptor cells. Furthermore, there is early evidence that these transplanted cells provide improved visual function. These groundbreaking studies provide proof of concept that stem cell therapy is a viable method of visual rehabilitation among eyes with retinitis pigmentosa. Further studies are required to optimize these techniques in human application. This review focuses on stem cell therapy as a new approach for vision restitution in retinitis pigmentosa.

  20. Retinitis pigmentosa and ocular blood flow

    PubMed Central

    2012-01-01

    Is the concept of integrative, preventive and personalised medicine applicable to the relationship between retinitis pigmentosa (RP) and ocular blood flow (OBF)? RP encompasses a group of hereditary diseases of the posterior segment of the eye characterised by degeneration, atrophy and finally loss of photoreceptors and retinal pigment epithelium, leading to progressive visual loss. Many different mutations affecting different genes can lead to the clinical picture of RP. Even though the disease has a clear genetic background, there are obviously other factors influencing the manifestation and progression of RP. In this review, we focus on the role of OBF. There is evidence that, in PR patients, OBF is more reduced than one would expect secondary to the retinal atrophy. The main cause of this additional component seems to be primary vascular dysregulation (PVD) syndrome. As PVD syndrome is partly treatable, a vascular evaluation of RP patients is meaningful. Based on the outcome, a targeted individualised, preventive or supportive treatment might be introduced in selected RP patients. PMID:23199279

  1. Halting progressive neurodegeneration in advanced retinitis pigmentosa.

    PubMed

    Koch, Susanne F; Tsai, Yi-Ting; Duong, Jimmy K; Wu, Wen-Hsuan; Hsu, Chun-Wei; Wu, Wei-Pu; Bonet-Ponce, Luis; Lin, Chyuan-Sheng; Tsang, Stephen H

    2015-09-01

    Hereditary retinal degenerative diseases, such as retinitis pigmentosa (RP), are characterized by the progressive loss of rod photoreceptors followed by loss of cones. While retinal gene therapy clinical trials demonstrated temporary improvement in visual function, this approach has yet to achieve sustained functional and anatomical rescue after disease onset in patients. The lack of sustained benefit could be due to insufficient transduction efficiency of viral vectors ("too little") and/or because the disease is too advanced ("too late") at the time therapy is initiated. Here, we tested the latter hypothesis and developed a mouse RP model that permits restoration of the mutant gene in all diseased photoreceptor cells, thereby ensuring sufficient transduction efficiency. We then treated mice at early, mid, or late disease stages. At all 3 time points, degeneration was halted and function was rescued for at least 1 year. Not only do our results demonstrate that gene therapy effectively preserves function after the onset of degeneration, our study also demonstrates that there is a broad therapeutic time window. Moreover, these results suggest that RP patients are treatable, despite most being diagnosed after substantial photoreceptor loss, and that gene therapy research must focus on improving transduction efficiency to maximize clinical impact.

  2. Halting progressive neurodegeneration in advanced retinitis pigmentosa

    PubMed Central

    Koch, Susanne F.; Tsai, Yi-Ting; Duong, Jimmy K.; Wu, Wen-Hsuan; Hsu, Chun-Wei; Wu, Wei-Pu; Bonet-Ponce, Luis; Lin, Chyuan-Sheng; Tsang, Stephen H.

    2015-01-01

    Hereditary retinal degenerative diseases, such as retinitis pigmentosa (RP), are characterized by the progressive loss of rod photoreceptors followed by loss of cones. While retinal gene therapy clinical trials demonstrated temporary improvement in visual function, this approach has yet to achieve sustained functional and anatomical rescue after disease onset in patients. The lack of sustained benefit could be due to insufficient transduction efficiency of viral vectors (“too little”) and/or because the disease is too advanced (“too late”) at the time therapy is initiated. Here, we tested the latter hypothesis and developed a mouse RP model that permits restoration of the mutant gene in all diseased photoreceptor cells, thereby ensuring sufficient transduction efficiency. We then treated mice at early, mid, or late disease stages. At all 3 time points, degeneration was halted and function was rescued for at least 1 year. Not only do our results demonstrate that gene therapy effectively preserves function after the onset of degeneration, our study also demonstrates that there is a broad therapeutic time window. Moreover, these results suggest that RP patients are treatable, despite most being diagnosed after substantial photoreceptor loss, and that gene therapy research must focus on improving transduction efficiency to maximize clinical impact. PMID:26301813

  3. The transplantation of human fetal neuroretinal cells in advanced retinitis pigmentosa patients: results of a long-term safety study.

    PubMed

    Das, T; del Cerro, M; Jalali, S; Rao, V S; Gullapalli, V K; Little, C; Loreto, D A; Sharma, S; Sreedharan, A; del Cerro, C; Rao, G N

    1999-05-01

    The purpose of this study was to determine the long-term safety of transplanting human fetal neuroretinal cells (14 to 18 week gestational age) into a series of patients with advanced retinitis pigmentosa (RP). After obtaining informed consent, both hosts and mothers of donors were screened for transmissible diseases. Pre- and postoperative clinical exams, visual acuity, electroretinograms, and fluorescein angiograms were performed and visual field testing was attempted in each case. Surgically, an anterior approach through pars plana ciliaris was used. A retinotomy was performed in the paramacular area and a two-function cannula was introduced into the subretinal space to deliver a suspension of donor cells. The cell suspension carried approximately 4000 cells/microl; the volume injected did not exceed 150 microl. The patients were examined for periods ranging from 12 to 40 months posttransplantation. To date, no evidence of inflammation, infection, or overt rejection of the graft was noted in the host eye, neither was any change observed in the contralateral, unoperated eye. In conclusion, neuroretinal cells were injected into the subretinal space of 14 patients with advanced RP with no clinical appearance of detrimental effects at the time of surgery or up to 40 months postinjection except in 1 patient who developed retinal detachment. This sets the stage for a phase II clinical trial to determine the possible beneficial effects of this procedure in patients blinded by degenerative retinal disease.

  4. Recessive mutations in the gene encoding the beta-subunit of rod phosphodiesterase in patients with retinitis pigmentosa.

    PubMed

    McLaughlin, M E; Sandberg, M A; Berson, E L; Dryja, T P

    1993-06-01

    We have found four mutations in the human gene encoding the beta-subunit of rod cGMP phosphodiesterase (PDE beta) that cosegregate with autosomal recessive retinitis pigmentosa, a degenerative disease of photoreceptors. In one family two affected siblings both carry allelic nonsense mutations at codons 298 and 531. Affected individuals have abnormal rod and cone electroretinograms. PDE beta is the second member of the phototransduction cascade besides rhodopsin that is absent or altered as a cause of retinitis pigmentosa, suggesting that other members of this pathway may be defective in other forms of this disease.

  5. Genes and mutations causing retinitis pigmentosa

    PubMed Central

    Daiger, SP; Sullivan, LS; Bowne, SJ

    2013-01-01

    Retinitis pigmentosa (RP) is a heterogeneous set of inherited retinopathies with many disease-causing genes, many known mutations, and highly varied clinical consequences. Progress in finding treatments is dependent on determining the genes and mutations causing these diseases, which includes both gene discovery and mutation screening in affected individuals and families. Despite the complexity, substantial progress has been made in finding RP genes and mutations. Depending on the type of RP, and the technology used, it is possible to detect mutations in 30–80% of cases. One of the most powerful approaches to genetic testing is high-throughput ‘deep sequencing’, that is, next-generation sequencing (NGS). NGS has identified several novel RP genes but a substantial fraction of previously unsolved cases have mutations in genes that are known causes of retinal disease but not necessarily RP. Apparent discrepancy between the molecular defect and clinical findings may warrant reevaluation of patients and families. In this review, we summarize the current approaches to gene discovery and mutation detection for RP, and indicate pitfalls and unsolved problems. Similar considerations apply to other forms of inherited retinal disease. PMID:23701314

  6. A Psychophysical Test for Retinitis Pigmentosa.

    ERIC Educational Resources Information Center

    Corwin, Thomas R; Mancini, Michael

    A new test designed to detect an hereditary eye disease called retinitis pigmentosa (RP) is described. This condition is revealed by pigmentation in the retina, but early diagnosis is difficult because the symptoms are subtle, and since it is genetically recessive it frequently occurs in families with no history of early blindness. In many cases…

  7. A Psychophysical Test for Retinitis Pigmentosa.

    ERIC Educational Resources Information Center

    Corwin, Thomas R; Mancini, Michael

    A new test designed to detect an hereditary eye disease called retinitis pigmentosa (RP) is described. This condition is revealed by pigmentation in the retina, but early diagnosis is difficult because the symptoms are subtle, and since it is genetically recessive it frequently occurs in families with no history of early blindness. In many cases…

  8. The Retinitis Pigmentosa Student: Selected Aspects.

    ERIC Educational Resources Information Center

    Sullivan, Franklin N.

    1984-01-01

    The characteristic features of RP (retinitis pigmentosa-an untreatable conditions usually resulting in night blindness) are discussed and functioning considerations in the classroom (including the use of protective devices and mobility aids) are noted. Classroom modifications such as darklined paper and black pens are suggested. (CL)

  9. The Retinitis Pigmentosa Student: Selected Aspects.

    ERIC Educational Resources Information Center

    Sullivan, Franklin N.

    1984-01-01

    The characteristic features of RP (retinitis pigmentosa-an untreatable conditions usually resulting in night blindness) are discussed and functioning considerations in the classroom (including the use of protective devices and mobility aids) are noted. Classroom modifications such as darklined paper and black pens are suggested. (CL)

  10. Homozygous mutation in MERTK causes severe autosomal recessive retinitis pigmentosa.

    PubMed

    Ksantini, Mohamed; Lafont, Estèle; Bocquet, Béatrice; Meunier, Isabelle; Hamel, Christian P

    2012-01-01

    Gene identification in retinitis pigmentosa is a prerequisite to future therapies. Accordingly, autosomal recessive retinitis pigmentosa families were genotyped to search for causative mutations. Members of a consanguineous Moroccan family had standard ophthalmologic examination, optical coherence tomography-3 scan, autofluorescence testing, and electroretinogram. Their DNA was genotyped with the 250K SNP microchip (Affymetrix) and homozygosity mapping was done. MERTK exons were polymerase chain reaction amplified and sequenced. Two sisters and one brother out of 6 siblings had rod cone dystrophy type of retinitis pigmentosa. Salient features were night blindness starting in early infancy, dot-like whitish deposits in fovea and macula with corresponding autofluorescent dots in youngest patients, decreased visual acuity, and cone responses higher than rod responses at electroretinogram. The patients were homozygous in regions from chromosomes 2 and 8, but only that of chromosome 2 was inherited from a common ancestor. Sequencing of the MERTK gene belonging to the chromosome 2 region showed that the 3 affected patients carried a novel homozygous mutation in exon 17, c.2323C>T, leading to p.Arg775X, while their unaffected brothers and sister, parents, and paternal grandfather were heterozygous. MERTK mutations lead to severe retinitis pigmentosa with discrete dot-like autofluorescent deposits at early stages, which are a hallmark of this MERTK-specific dystrophy.

  11. Intravitreal Injection of Bone Marrow Mesenchymal Stem Cells in Patients with Advanced Retinitis Pigmentosa; a Safety Study

    PubMed Central

    Satarian, Leila; Nourinia, Ramin; Safi, Sare; Kanavi, Mozhgan Rezaei; Jarughi, Neda; Daftarian, Narsis; Arab, Leila; Aghdami, Nasser; Ahmadieh, Hamid; Baharvand, Hossein

    2017-01-01

    Purpose: To examine the safety of a single intravitreal injection of autologous bone Marrow Mesenchymal stem cells (MSCs) in patients with advanced retinitis pigmentosa (RP). Methods: A prospective, phase I, nonrandomized, open-label study was conducted on 3 eyes of 3 volunteers with advanced RP. Visual acuity, slit-lamp examination, fundus examination, optical coherence tomography, fundus auto-fluorescence, fluorescein angiography and multifocal electroretinography were performed before and after an intravitreal injection of approximately one-million MSCs. The patients were followed for one year. Further evaluation of MSCs was performed by injection of these cells into the mouse vitreous cavity. Results: No, adverse events were observed in eyes of 2 out of 3 patients after transplantation of MSCs. These patients reported improvements in perception of the light after two weeks, which lasted for 3 months. However, severe fibrous tissue proliferation was observed in the vitreous cavity and retrolental space of the third patient's eye, which led to tractional retinal detachment (TRD), iris neovascularization and formation of mature cataract. Injection of this patient's MSCs into the vitreous cavity of mice also resulted in fibrosis; however, intravitreal injections of the two other patients' cells into the mouse vitreous did not generate any fibrous tissue. Conclusion: Intravitreal injection of autologous bone marrow MSCs into patients' eyes with advanced RP does not meet safety standards. Major side effects of this therapy can include fibrosis and TRD. We propose thorough evaluation of MSCs prior to transplantation by intravitreal injection in the laboratory animals.\\ PMID:28299008

  12. Intravitreal Injection of Bone Marrow Mesenchymal Stem Cells in Patients with Advanced Retinitis Pigmentosa; a Safety Study.

    PubMed

    Satarian, Leila; Nourinia, Ramin; Safi, Sare; Kanavi, Mozhgan Rezaei; Jarughi, Neda; Daftarian, Narsis; Arab, Leila; Aghdami, Nasser; Ahmadieh, Hamid; Baharvand, Hossein

    2017-01-01

    To examine the safety of a single intravitreal injection of autologous bone Marrow Mesenchymal stem cells (MSCs) in patients with advanced retinitis pigmentosa (RP). A prospective, phase I, nonrandomized, open-label study was conducted on 3 eyes of 3 volunteers with advanced RP. Visual acuity, slit-lamp examination, fundus examination, optical coherence tomography, fundus auto-fluorescence, fluorescein angiography and multifocal electroretinography were performed before and after an intravitreal injection of approximately one-million MSCs. The patients were followed for one year. Further evaluation of MSCs was performed by injection of these cells into the mouse vitreous cavity. No, adverse events were observed in eyes of 2 out of 3 patients after transplantation of MSCs. These patients reported improvements in perception of the light after two weeks, which lasted for 3 months. However, severe fibrous tissue proliferation was observed in the vitreous cavity and retrolental space of the third patient's eye, which led to tractional retinal detachment (TRD), iris neovascularization and formation of mature cataract. Injection of this patient's MSCs into the vitreous cavity of mice also resulted in fibrosis; however, intravitreal injections of the two other patients' cells into the mouse vitreous did not generate any fibrous tissue. Intravitreal injection of autologous bone marrow MSCs into patients' eyes with advanced RP does not meet safety standards. Major side effects of this therapy can include fibrosis and TRD. We propose thorough evaluation of MSCs prior to transplantation by intravitreal injection in the laboratory animals.\\.

  13. The search for mutations in the gene for the beta subunit of the cGMP phosphodiesterase (PDEB) in patients with autosomal recessive retinitis pigmentosa

    SciTech Connect

    Riess, O.; Weber, B.; Hayden, M.R. ); Noerremoelle, A. ); Musarella, M.A. )

    1992-10-01

    The finding of a mutation in the beta subunit of the cyclic GMP (cGMP) phosphodiesterase gene causing retinal degeneration in mice (the Pdeb gene) prompted a search for disease-causing mutations in the human phosphodiesterase gene (PDEB gene) in patients with retinitis pigmentosa. All 22 exons including 196 bp of the 5[prime] region of the PDEB gene have been assessed for mutations by using single-strand conformational polymorphism analysis in 14 patients from 13 unrelated families with autosomal recessive retinitis pigmentosa (ARRP). No disease-causing mutations were found in this group of affected individuals of seven different ancestries. However, a frequent intronic and two exonic polymorphisms (Leu[sup 489][yields]Gln and Gly[sup 842][yields]Gly) were identified. Segregation analysis using these polymorphic sites excludes linkage of ARRP to the PDEB gene in a family with two affected children. 43 refs., 3 figs., 2 tabs.

  14. A case of CRB1-negative Coats-like retinitis pigmentosa.

    PubMed

    Sarao, Valentina; Veritti, Daniele; Prosperi, Raffaele; Pignatto, Silvia; Lanzetta, Paolo

    2013-08-01

    Retinitis pigmentosa is a heterogeneous group of ocular diseases that causes progressive degeneration of the photoreceptor cells mainly affecting the rods of the peripheral retina. The association between retinitis pigmentosa and exudative retinopathy was first described in 1956 and has been called "Coats-like retinitis pigmentosa." Mutations in the Crumbs homolog 1 (CRB1) gene have been reported as a risk factor for developing Coats-like changes in patients with autosomal recessive retinitis pigmentosa. We report the case of a 15-year-old girl affected by CRB1 gene-negative retinitis pigmentosa and Coats-like exudative vasculopathy who was successfully treated with laser photocoagulation. Copyright © 2013 American Association for Pediatric Ophthalmology and Strabismus. Published by Mosby, Inc. All rights reserved.

  15. Retinitis pigmentosa: clinical observations and correlations.

    PubMed Central

    Pruett, R C

    1983-01-01

    This thesis presents the results of a study of 384 eyes of 192 patients with a mean age of 39.1 years who presented with typical retinitis pigmentosa. The major findings are outlined below, together with suggested hypotheses: Cataract was found in 46.4% of the eyes. Among these, 93.6% showed posterior subcapsular opacification. The incidence of cataract increased with age. The vitreous degeneration that is characteristic of the RP syndrome and begins in childhood was described as showing dust-like, particulate matter throughout the gel; posterior vitreous separation; formation of a posterior matrix of coarse, white, interconnected strands and opacities; and final collapse of the residual gel. Ultrastructural studies of vitreous material from eight eyes revealed that the particles were isolated pigment granules and the coarse strands were composed of condensed collagen fibers. Notwithstanding the vitreous degeneration and prevalence of myopia in RP, neurosensory retinal breaks and/or rhegmatogenous detachment were found in only 7 (1.8%) of the 384 eyes studied. Premature separation of the vitreous from the retina, absence of lattice retinal degeneration, and perhaps a stronger than normal RPE-neurosensory retinal bond are thought to be possible protective factors. Rather than searching for a "toxin," elaborated by diseased retina, that causes vitreous degeneration and cataract formation, it is suggested that the ocular media be studied for an absence of moieties that are normally produced by healthy retina for vitreous and lens maintenance. The classic criteria for diagnosis of RP were met by 96.3% of eyes that showed retinal vascular attenuation and by 52.0% that showed pallor of the optic disc. Less frequent manifestations included solitary retinal hemorrhage, peripheral microaneurysms, telangiectasia, and fluorescein leakage at the macula and disc. Seven additional cases with a Coats'-like retinal detachment were added to the 14 already presented in the

  16. RPGR is mutated in patients with a complex X linked phenotype combining primary ciliary dyskinesia and retinitis pigmentosa

    PubMed Central

    Moore, A; Escudier, E; Roger, G; Tamalet, A; Pelosse, B; Marlin, S; Clément, A; Geremek, M; Delaisi, B; Bridoux, A‐M; Coste, A; Witt, M; Duriez, B; Amselem, S

    2006-01-01

    Introduction Primary ciliary dyskinesia (PCD) is a rare disease classically transmitted as an autosomal recessive trait and characterised by recurrent airway infections due to abnormal ciliary structure and function. To date, only two autosomal genes, DNAI1 and DNAH5 encoding axonemal dynein chains, have been shown to cause PCD with defective outer dynein arms. Here, we investigated one non‐consanguineous family in which a woman with retinitis pigmentosa (RP) gave birth to two boys with a complex phenotype combining PCD, discovered in early childhood and characterised by partial dynein arm defects, and RP that occurred secondarily. The family history prompted us to search for an X linked gene that could account for both conditions. Results We found perfect segregation of the disease phenotype with RP3 associated markers (Xp21.1). Analysis of the retinitis pigmentosa GTPase regulator gene (RPGR) located at this locus revealed a mutation (631_IVS6+9del) in the two boys and their mother. As shown by study of RPGR transcripts expressed in nasal epithelial cells, this intragenic deletion, which leads to activation of a cryptic donor splice site, predicts a severely truncated protein. Conclusion These data provide the first clear demonstration of X linked transmission of PCD. This unusual mode of inheritance of PCD in patients with particular phenotypic features (that is, partial dynein arm defects and association with RP), which should modify the current management of families affected by PCD or RP, unveils the importance of RPGR in the proper development of both respiratory ciliary structures and connecting cilia of photoreceptors. PMID:16055928

  17. Analysis of the PRPF31 Gene in Spanish Autosomal Dominant Retinitis Pigmentosa Patients: A Novel Genomic Rearrangement.

    PubMed

    Martin-Merida, Inmaculada; Sanchez-Alcudia, Rocio; Fernandez-San Jose, Patricia; Blanco-Kelly, Fiona; Perez-Carro, Raquel; Rodriguez-Jacy da Silva, Luciana; Almoguera, Berta; Garcia-Sandoval, Blanca; Lopez-Molina, Maria Isabel; Avila-Fernandez, Almudena; Carballo, Miguel; Corton, Marta; Ayuso, Carmen

    2017-02-01

    The aim was to determine the prevalence of PRPF31 mutations in a cohort of Spanish autosomal dominant retinitis pigmentosa (adRP) families to deepen knowledge of the pathogenic mechanisms underlying the disease and to assess genotype-phenotype correlations. A cohort of 211 adRP patients was screened for variants in PRPF31 by using a combined strategy comprising next-generation sequencing approaches and copy-number variation (CNV) analysis. Quantitative RT-PCR and CNV analysis of the regulatory MSR1 element were also performed to assess PRPF31 gene expression. Phenotype was assessed by using ophthalmologic examination protocols. Fifteen different causative mutations and genomic rearrangements were identified, revealing five novel mutations. Prevalence of PRPF31 mutations, genomic rearrangements, and lack of penetrance were 7.6%, 1.9%, and 66.7%, respectively. Interestingly, we identified a tandem duplication and a partial PRPF31 deletion in different affected individuals from the same family. PRPF31 gene expression was significantly decreased in symptomatic cases carrying either PRPF31 duplication or deletion as compared to controls. The 4 MSR1 allele in cis with the PRPF31 wild-type allele was apparently a protective factor. The mutated phenotype varied from no symptoms to typical retinitis pigmentosa with variable onset and course depending on the kind of mutation, with the duplication case the most severe. In view of the high genetic heterogeneity of PRPF31 mutations, the screening must include the entire gene, as well as CNV assays, to detect large rearrangements. This is the first report of a variable phenotype correlation as well as a gross duplication and deletion within the same family.

  18. [Arthrogryposis multiplex congenita and retinitis pigmentosa].

    PubMed

    Stübiger, N; Biester, S; Deuter, C; Zrenner, E; Besch, D

    2009-12-01

    Arthrogryposis multiplex congenita (AMC) is a heterogeneous pattern of symptoms consisting of clinically different types. AMC is a non-progressive condition, which is characterized by congenital contracture of several joints in different body areas and may also occur as a manifestation of other syndromes. In such syndromes retinopathy as an ophthalmological manifestation of AMC has been described in the literature in only two patients. A 12-year-old girl with AMC presented with progressive visual loss since 1 year. Visual acuity was 0.5 in the right and 0.8 in the left eye. Visual fields were concentrically constricted. Funduscopy revealed an atrophic retinal pigment epithelium of the whole fundus with vital optic discs. In the scotopic electroretinogram (ERG) amplitudes were dramatically decreased or absent and cone signals were delayed. The multifocal ERG (mfERG) presented pathologically reduced amplitudes in the macular region as well as in the periphery. Examinations 5 and 8 years later revealed a reduction of visual acuity to 0.05 in the right and to 0.1 in the left eye, in addition the results of perimetry and of the Ganzfeld-ERG had deceased and the mfERG was no longer measurable. This young female demonstrated an AMC in combination with retinitis pigmentosa, but other disease manifestations or cerebral retardation could not be found. We present here an unusual case of what seems to be a new athrogryposis syndrome.

  19. LONG-TERM FOLLOW-UP OF PATIENTS WITH RETINITIS PIGMENTOSA TYPE 12 CAUSED BY CRB1 MUTATIONS: A Severe Phenotype With Considerable Interindividual Variability.

    PubMed

    Mathijssen, Inge B; Florijn, Ralph J; van den Born, L Ingeborgh; Zekveld-Vroon, Renate C; Ten Brink, Jacoline B; Plomp, Astrid S; Baas, Frank; Meijers-Heijboer, Hanne; Bergen, Arthur A B; van Schooneveld, Mary J

    2017-01-01

    To examine the long-term clinical course and variability in a large pedigree segregating CRB1 type autosomal recessive retinitis pigmentosa. An observational case study of 30 patients with CRB1 type autosomal recessive retinitis pigmentosa, homozygous for the CRB1 c.3122T > C; p.(Met1041Thr) mutation from a Dutch genetically isolated population in which the CRB1 gene was originally identified. The authors evaluated medical records, analyzed a questionnaire, and performed a comprehensive ophthalmic examination, including optical coherence tomography. Mean follow-up was 19 years (range 0-45 years, SD 15 years). With aging, patients showed progressive visual decline, deterioration of visual fields, increasing narrowing of the anterior chamber, increased prevalence of cataract, and an increase in the amount of intraretinal pigmentations. Fifty percent of patients had a visual acuity of ≤0.3 at Age 18 and of ≤0.1 at Age 35. Electroretinogram responses were severely reduced or absent already at a young age and optical coherence tomography showed increased retinal thickness with often cystoid maculopathy at young age, and thinning of the retina and disorientation of the photoreceptor layer in the late stages. The clinical course showed considerable interindividual variability, but intraindividual similarity between both eyes was the rule. The wide and variable clinical spectrum in patients with the same CRB1 mutation supports the hypothesis that the CRB1 type autosomal recessive retinitis pigmentosa-phenotype is modulated by other factors. The clinical variability will make it harder to evaluate the effect of (upcoming) therapies for retinitis pigmentosa, although because of the intraindividual similarity between both eyes, the contralateral eye can be used as an excellent internal control.

  20. Unilateral retinitis pigmentosa. A case report.

    PubMed

    Nazar, C; Feldman, M; González, R; Espinoza, R

    2017-06-01

    A 27-year-old woman with a history of nyctalopia and constriction of visual field of the right eye. The ophthalmological examination showed a visual field and electroretinogram that were compatible with unilateral retinitis pigmentosa (RP). After a one year follow-up, the unilateral condition remained. Unilateral retinitis pigmentosa is a rare condition, with a frequency between 0.2%-5% of the RP. It mainly affects women and older age groups than bilateral RP. For a definitive diagnosis, it is necessary to have a funduscopy and electroretinogram (ERG) altered unilaterally, and exclude infectious, inflammatory, and vascular causes. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Functional characterisation and serial imaging of abnormal fundus autofluorescence in patients with retinitis pigmentosa and normal visual acuity.

    PubMed

    Robson, A G; Saihan, Z; Jenkins, S A; Fitzke, F W; Bird, A C; Webster, A R; Holder, G E

    2006-04-01

    To characterise and monitor abnormal fundus autofluorescence (AF) in patients with retinitis pigmentosa (RP) who have good visual acuity. 21 patients with a clinical diagnosis of RP were examined. All had rod-cone dystrophy (ISCEV standard electroretinograms (ERGs)), visual acuity of 6/9 or better, and manifested a parafoveal ring of high density fundus AF. Repeat AF imaging was performed after periods of between 2 years and 5 years in 12 patients. Pattern ERG (PERG) and multifocal ERG (mfERG) were performed in 20 cases. Visual fields (VF), photopic and scotopic fine matrix mapping and small field PERGs were performed in representative cases. The rings of high density AF varied in size between patients (from 4 degrees -16 degrees diameter). MfERGs showed relative preservation over the central macular area, correlating with the size of AF ring and with PERG and psychophysical data. Progressive constriction of the AF ring was demonstrated at follow up in three patients. Serial PERG, mfERG, and VFs, performed in one of these cases, showed evidence of deterioration concordant with ring constriction. High density rings of AF, seen in some patients with RP with good visual acuity, demarcate areas of preserved central photopic function. MfERGs correlate with the area encircled by high density AF and the PERG data. The size of the ring of AF can show progressive constriction accompanied by increasing macular dysfunction.

  2. Thickness of receptor and post-receptor retinal layers in patients with retinitis pigmentosa measured with frequency-domain optical coherence tomography.

    PubMed

    Hood, Donald C; Lin, Christine E; Lazow, Margot A; Locke, Kirsten G; Zhang, Xian; Birch, David G

    2009-05-01

    To better understand the effects of retinitis pigmentosa (RP) on post-receptor anatomy, the thicknesses of the receptor, inner nuclear, retinal ganglion cell (RGC), and retinal nerve fiber layers (RNFL) were measured with frequency-domain optical coherence tomography (fdOCT). FdOCT scans were obtained from the horizontal midline in 30 patients with RP and 23 control subjects of comparable age. Raw images were exported and the thicknesses of photoreceptor/RPE, inner nuclear, RGC plus inner plexiform, and nerve fiber layers were measured with a manual segmentation procedure aided by a computer program. The RNFL thickness was also measured in 20 controls and 25 patients using circular peripapillary fdOCT scans. Results from controls were consistent with known anatomy. In patients with RP, the pattern of photoreceptor loss with eccentricity was consistent with the field constriction characteristic of RP. INL and RGC layer measures were comparable to normal subjects, although some patients showed slightly thicker RGC layers. However, RNFL layer thickness was significantly greater than normal; a majority of patients showed a thicker RFNL on both horizontal midline scans and peripapillary scans. To make optimal use of OCT RNFL thickness as a measure of the integrity of RGCs in patients with RP, a better understanding of the causes of the thickening seen in the majority of the patients is needed. As the RGC layer thickness can be measured with fdOCT, RGC layer thickness may turn out to be a more direct and valid indicator of the presence of RGCs in patients with RP.

  3. Spontaneous dislocation of posterior chamber intraocular lenses (PC IOLs) in patients with retinitis pigmentosa – Case series

    PubMed Central

    Masket, Samuel; Bostanci Ceran, Basak; Fram, Nicole R.

    2011-01-01

    Purpose To report the outcomes of intraocular lens (IOL) dislocation management in 6 cases with Retinitis Pigmentosa (RP). Setting Private practice, Los Angeles, USA. Design Retrospective interventional case series. Methods The medical reports of six eyes of four RP patients with capsule bag fixated posterior chamber IOL dislocation were retrospectively reviewed. Pre-operative data included demographics, systemic or ocular disorders, history of trauma, previous intraocular surgery and pre-operative visual acuity. Outcome measures included the type of surgery, surgical complications, elevation of intraocular pressure (IOP), ocular inflammation, cystoid macular edema (CME) and IOL dislocation at 3 months or greater post-operatively. Results The medical records of six eyes of four patients operated on between December 2009 and May 2011 were evaluated. In four cases, dislocated PC IOL implants were sutured to the sclera. In two eyes of one patient anterior chamber IOLs (AC IOLs) were implanted after PC IOLs were explanted. One eye developed CME during the follow-up period. Despite modest tilt in one case and modest decentration in another, stability and centration of the IOLs was excellent during the follow-up period. No eyes had intraocular inflammation requiring long term medical treatment, new onset glaucoma or retinal detachment. Mean follow-up time was 6.9 months (range 3-20). Conclusions Cataract surgeons should be aware of the increased risk for decentration and malposition of PC IOLs in patients with RP. Satisfactory results can be achieved by fixation of the PC IOL or AC IOL implantation. PMID:23960970

  4. The Genetic Basis of Pericentral Retinitis Pigmentosa-A Form of Mild Retinitis Pigmentosa.

    PubMed

    Comander, Jason; Weigel-DiFranco, Carol; Maher, Matthew; Place, Emily; Wan, Aliete; Harper, Shyana; Sandberg, Michael A; Navarro-Gomez, Daniel; Pierce, Eric A

    2017-10-05

    Pericentral retinitis pigmentosa (RP) is an atypical form of RP that affects the near-peripheral retina first and tends to spare the far periphery. This study was performed to further define the genetic basis of this phenotype. We identified a cohort of 43 probands with pericentral RP based on a comprehensive analysis of their retinal phenotype. Genetic analyses of DNA samples from these patients were performed using panel-based next-generation sequencing, copy number variations, and whole exome sequencing (WES). Mutations provisionally responsible for disease were found in 19 of the 43 families (44%) analyzed. These include mutations in RHO (five patients), USH2A (four patients), and PDE6B (two patients). Of 28 putatively pathogenic alleles, 15 (54%) have been previously identified in patients with more common forms of typical RP, while the remaining 13 mutations (46%) were novel. Burden testing of WES data successfully identified HGSNAT as a cause of pericentral RP in at least two patients, suggesting it is also a relatively common cause of pericentral RP. While additional sequencing might uncover new genes specifically associated with pericentral RP, the current results suggest that genetically pericentral RP is not a separate clinical entity, but rather is part of the spectrum of mild RP phenotypes.

  5. ASYMMETRIC CONE DISTRIBUTION AND ITS CLINICAL APPEARANCE IN RETINITIS PIGMENTOSA.

    PubMed

    Nakagawa, Satoko; Oishi, Akio; Ogino, Ken; Morooka, Satoshi; Oishi, Maho; Sugahara, Masako; Yoshimura, Nagahisa

    2016-07-01

    To report the characteristic changes of fundus autofluorescence in the nasal retina of patients with retinitis pigmentosa. We investigated 113 eyes of 113 patients with retinitis pigmentosa. We obtained wide-field fundus autofluorescence images and evaluated the status of the retina nasal to the optic disk. The patients were divided into the following three groups: those without nasal sparing (advanced), those with nasal sparing, and those with larger intact areas in addition to the nasal retina (early). Visual acuity, visual field area, age, and the duration of the symptom were compared among the groups. Twenty eyes (17.7%), 51 (45.1%), and 42 (37.1%) were classified as early, nasal sparing, and advanced, respectively. The nasal retina was essentially preserved in the early group. The clinical characteristics' analysis suggested that the disease progression appears from that represented by early groups, then nasal sparing groups, and finally advanced groups. The authors found that the nasal sparing pattern bears a close resemblance to the previously reported cone photoreceptor distribution. Wide-field fundus autofluorescence imaging detected nasal sparing in retinitis pigmentosa. The characteristic fundus autofluorescence pattern should reflect cone photoreceptor distribution in the human retina. This finding may be an example of the clinical appearance of asymmetric photoreceptor distribution.

  6. Long-term follow-up of patients with retinitis pigmentosa (RP) receiving intraocular ciliary neurotrophic factor implants

    PubMed Central

    Birch, David G.; Bennett, Lea D.; Duncan, Jacque L.; Weleber, Richard G.; Pennesi, Mark E.

    2016-01-01

    Purpose To evaluate the long-term efficacy of ciliary neurotrophic factor delivered via an intraocular encapsulated cell implant for the treatment of retinitis pigmentosa (RP). Design Long-term follow up of a multicenter, sham-controlled study. Methods Thirty-six patients at three CNTF4 sites were randomly assigned to receive a high- or low- dose implant in one eye and sham surgery in the fellow eye. The primary endpoint (change in visual field sensitivity at 12 months) has been reported previously.1 Here we report long-term visual acuity, visual field and optical coherence tomography (OCT) outcomes in 24 patients either retaining or explanting the device at 24 months relative to sham-treated eyes. Results Eyes retaining the implant showed significantly greater visual field loss from baseline than either explanted eyes or sham eyes through 42 months. By 60 months and continuing through 96 months, visual field loss was comparable among sham-treated eyes, eyes retaining the implant and explanted eyes, as was visual acuity and OCT macular volume. Conclusions Over the short term, ciliary neurotrophic factor released continuously from an intra-vitreal implant lead to loss of total visual field sensitivity that was greater than the natural progression in the sham-treated eye. This additional loss of sensitivity related to the active implant was reversible when the implant was removed. Over the long term (60 – 96 months), there was no evidence of efficacy for visual acuity, visual field sensitivity or OCT measures of retinal structure. PMID:27457255

  7. Retinal Prosthesis System for Advanced Retinitis Pigmentosa: A Health Technology Assessment.

    PubMed

    2016-01-01

    Retinitis pigmentosa is a group of genetic disorders that involves the breakdown and loss of photoreceptors in the retina, resulting in progressive retinal degeneration and eventual blindness. The Argus II Retinal Prosthesis System is the only currently available surgical implantable device approved by Health Canada. It has been shown to improve visual function in patients with severe visual loss from advanced retinitis pigmentosa. The objective of this analysis was to examine the clinical effectiveness, cost-effectiveness, budget impact, and safety of the Argus II system in improving visual function, as well as exploring patient experiences with the system. We performed a systematic search of the literature for studies examining the effects of the Argus II retinal prosthesis system in patients with advanced retinitis pigmentosa, and appraised the evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria, focusing on visual function, functional outcomes, quality of life, and adverse events. We developed a Markov decision-analytic model to assess the cost-effectiveness of the Argus II system compared with standard care over a 10-year time horizon. We also conducted a 5-year budget impact analysis. We used a qualitative design and an interview methodology to examine patients' lived experience, and we used a modified grounded theory methodology to analyze information from interviews. Transcripts were coded, and themes were compared against one another. One multicentre international study and one single-centre study were included in the clinical review. In both studies, patients showed improved visual function with the Argus II system. However, the sight-threatening surgical complication rate was substantial. In the base-case analysis, the Argus II system was cost-effective compared with standard care only if willingness-to-pay was more than $207,616 per quality-adjusted life-year. The 5-year budget

  8. Unilateral retinitis pigmentosa: 30 years follow-up

    PubMed Central

    Weller, Julia M; Michelson, Georg; Juenemann, Anselm G

    2014-01-01

    This case report depicts the clinical course of a female patient with unilateral retinitis pigmentosa (RP), who presented first in 1984 at the age of 43 years. At the beginning, there were cells in the vitreous leading to the diagnosis of uveitis with vasculitis. Within 30 years, the complete clinical manifestation of RP developed with bone spicule-shaped pigment deposits, pale optic disc, narrowed arterioles, cystoid macular oedema, posterior subcapsular cataract, concentric narrowing of the visual field and undetectable electroretinogram signal. At the age of 72 years, there are still no signs of retinal dystrophy in the other eye. PMID:24515232

  9. Retinal Prosthesis System for Advanced Retinitis Pigmentosa: A Health Technology Assessment

    PubMed Central

    Lee, Christine; Tu, Hong Anh; Weir, Mark; Holubowich, Corinne

    2016-01-01

    Background Retinitis pigmentosa is a group of genetic disorders that involves the breakdown and loss of photoreceptors in the retina, resulting in progressive retinal degeneration and eventual blindness. The Argus II Retinal Prosthesis System is the only currently available surgical implantable device approved by Health Canada. It has been shown to improve visual function in patients with severe visual loss from advanced retinitis pigmentosa. The objective of this analysis was to examine the clinical effectiveness, cost-effectiveness, budget impact, and safety of the Argus II system in improving visual function, as well as exploring patient experiences with the system. Methods We performed a systematic search of the literature for studies examining the effects of the Argus II retinal prosthesis system in patients with advanced retinitis pigmentosa, and appraised the evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria, focusing on visual function, functional outcomes, quality of life, and adverse events. We developed a Markov decision-analytic model to assess the cost-effectiveness of the Argus II system compared with standard care over a 10-year time horizon. We also conducted a 5-year budget impact analysis. We used a qualitative design and an interview methodology to examine patients’ lived experience, and we used a modified grounded theory methodology to analyze information from interviews. Transcripts were coded, and themes were compared against one another. Results One multicentre international study and one single-centre study were included in the clinical review. In both studies, patients showed improved visual function with the Argus II system. However, the sight-threatening surgical complication rate was substantial. In the base-case analysis, the Argus II system was cost-effective compared with standard care only if willingness-to-pay was more than $207,616 per quality-adjusted life

  10. Epidemiology of retinitis pigmentosa in Denmark.

    PubMed

    Haim, Marianne

    2002-01-01

    A nation-wide registration of Danish cases of retinitis pigmentosa (RP) provided 1890 persons diagnosed during the period 1850-1989. Prevalent at 1 January 1988 were 1301 persons (1:3943) comprising a multitude of different RP-types. Age specific prevalence rates demonstrated increasing rates of RP during the first four decades of life and a rather stable prevalence over the next 20-30 years. Corrected for incompleteness, a late decrease was found, reflecting an incomplete ascertainment of the oldest patients. A moving average method indicated an even later steady state value for the age-specific prevalence. The Danish prevalence figures were standardized according to the WHO World Standardized Prevalence Rates and compared with large studies from the USA and UK. No statistically significant difference was found. Usher syndrome was present in 12% of all RP-cases and Bardet-Biedl syndrome comprised 5%. Mental retardation was found in 144 cases (11%), mostly characterized by atypical RP. Nineteen per cent of patients affected by nonsystemic RP had an onset later than 30 years of age, whereas only a few per cent of persons with systemic RP had an RP onset after age 30 years. The Mendelian inheritance type of all cases was evaluated according to an unambiguous genetic classification, finding a larger amount of X-linked RP compared with other studies. Among nonsystemic RP-cases, 14.3% were found to be inherited as an X-linked trait whereas only 8.4% were autosomal dominantly inherited. The largest fraction was, as in previous materials, the simplex group (isolated cases) comprising 42.9% of the nonsystemic RP patients. Some factors influencing the results are discussed, with special emphasis on the problems associated with precise definitions of the Mendelian inheritance groups. A diagram according to the author's definition was constructed as a guideline ready for clinical application.

  11. RECURRENT CENTRAL SEROUS CHORIORETINOPATHY ASSOCIATED WITH RETINITIS PIGMENTOSA TREATED WITH CARBONIC ANHYDRASE INHIBITORS.

    PubMed

    Pomykala, Matthew; Rubin, Phillip; Rubin, Jeffrey S

    2016-01-01

    To describe a rare case of recurring central serous chorioretinopathy associated with retinitis pigmentosa successfully treated with oral acetazolamide. A 17-year-old male with retinitis pigmentosa who developed four separate episodes of central serous chorioretinopathy over a 12-month period. After the patient's fourth recurrence, he was treated with daily oral acetazolamide, which resulted in resolution of submacular fluid. He has had no subsequent recurrences while being maintained on alternating and then biweekly doses of oral acetazolamide. Recurrent central serous chorioretinopathy associated with retinitis pigmentosa is a rare occurrence. The presented case demonstrates that oral acetazolamide successfully treated and may have delayed recurrent episodes of central serous chorioretinopathy in the patient with retinitis pigmentosa.

  12. Choroidal thickness profiles in retinitis pigmentosa.

    PubMed

    Ayton, Lauren N; Guymer, Robyn H; Luu, Chi D

    2013-01-01

    Little quantitative information exists regarding the effect that retinitis pigmentosa (RP) has on the choroid. The aim of this study was to determine choroidal thickness profiles in patients with RP. Prospective. Forty-two RP and 22 control subjects participated in the study. RP patients had mild to severe disease, with a visual acuity range of logMAR 0.1 to no light perception. Images of the retina and choroid were obtained using the enhanced depth-imaging method and optical coherence tomography (OCT). Choroidal thickness measures were determined via manual segmentation of the OCT image. The thickness profiles of the normal and RP groups were compared. The associations between choroidal thickness, visual acuity and duration of RP were determined. The choroid was thickest in the control eyes at the subfoveal location (336.60 ± 70.42 μm), and the thickness gradually decreased towards the peripheral retina (temporal 8° = 295.55 ± 60.52 μm; nasal 8° = 251.68 ± 49.93 μm). In RP, the mean thickness was also greater at the fovea (215.60 ± 94.91 μm) than the temporal (191.66 ± 72.42 μm) and nasal (149.91 ± 57.42 μm) retina, but all values were significantly lower than those of the controls (P ≤ 0.001). Subfoveal choroidal thickness was significantly correlated with visual acuity (r = -0.46, P < 0.001) and duration of disease (r = -0.4, P = 0.001). Patients with RP have a thinner choroid than controls. Patients with poorer visual acuity or longer duration of symptoms tended to have thinner choroids. Knowledge of choroidal thickness profile in RP is important for the field of restorative vision research and the development of suprachoroidal retinal prostheses. © 2012 The Authors. Clinical and Experimental Ophthalmology © 2012 Royal Australian and New Zealand College of Ophthalmologists.

  13. Comprehensive molecular diagnosis of a large cohort of Japanese retinitis pigmentosa and Usher syndrome patients by next-generation sequencing.

    PubMed

    Oishi, Maho; Oishi, Akio; Gotoh, Norimoto; Ogino, Ken; Higasa, Koichiro; Iida, Kei; Makiyama, Yukiko; Morooka, Satoshi; Matsuda, Fumihiko; Yoshimura, Nagahisa

    2014-10-16

    Retinitis pigmentosa (RP), a major cause of blindness in developed countries, has multiple causative genes; its prevalence differs by ethnicity. Usher syndrome is the most common form of syndromic RP and is accompanied by hearing impairment. Although molecular diagnosis is challenging, recent technological advances such as targeted high-throughput resequencing are efficient screening tools. We performed comprehensive molecular testing in 329 Japanese RP and Usher syndrome patients by using a custom capture panel that covered the coding exons and exon/intron boundaries of all 193 known inherited eye disease genes combined with Illumina HiSequation 2500. Candidate variants were screened using systematic data analyses, and their potential pathogenicity was assessed according to the frequency of the variants in normal populations, in silico prediction tools, and compatibility with known phenotypes or inheritance patterns. Molecular diagnoses were made in 115/317 RP patients (36.3%) and 6/12 Usher syndrome patients (50%). We identified 104 distinct mutations, including 66 novel mutations. EYS, USH2A, and RHO were common causative genes. In particular, mutations in EYS accounted for 15.0% of the autosomal recessive/simplex RP patients or 10.7% of the entire RP cohort. Among the 189 previously reported mutations detected in the current study, 55 (29.1%) were found commonly in Japanese or other public databases and were excluded from molecular diagnoses. By screening a large cohort of patients, this study catalogued the genetic variations involved in RP and Usher syndrome in a Japanese population and highlighted the different distribution of causative genes among populations. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  14. Treatment with 9-cis β-carotene-rich powder in patients with retinitis pigmentosa: a randomized crossover trial.

    PubMed

    Rotenstreich, Ygal; Belkin, Michael; Sadetzki, Siegal; Chetrit, Angela; Ferman-Attar, Gili; Sher, Ifat; Harari, Ayelet; Shaish, Aviv; Harats, Dror

    2013-08-01

    Retinitis pigmentosa (RP) is the leading cause of incurable inherited blindness in the developed world, with an estimated prevalence of 1 in 3500 individuals. Therefore, it is important to develop new treatments for this disease. To determine the effect of oral treatment with 9-cis β-carotene on visual function of patients with RP. Randomized, double-masked, placebo-controlled, crossover clinical trial. University tertiary medical facility. Thirty-four patients with RP who were at least 18 years of age. Twenty-nine patients completed the study and were included in the analysis. Patients were treated daily for 90 days with capsules containing 300 mg of 9-cis β-carotene-ich alga Dunaliella bardawil (β-carotene, approximately 20 mg) or placebo (starch). Following a 90-day washout period, they were treated for 90 days with the other capsules. The primary outcomewas the change for both eyes from baseline to the end of each treatment in dark-adapted maximal electroretinographic b-wave amplitude. The secondary outcomes were the changes in light-adapted maximal b-wave amplitude, dark- and light-adapted visual field, and best-corrected visual acuity. The mean change in dark-adapted maximal b-wave amplitude relative to initial baseline was +8.4 μV for 9-cis β-carotene vs −.9 μV for placebo (P = .001). Ten participants (34.5%) had an increase of more than 10 μV for both eyes (range, 11-42 μV) after 9-cis β-carotene treatment compared with no participants after placebo treatment. The percentage change in light-adapted b-wave response was +17.8%for 9-cis β-carotene vs −.0% for placebo (P = .01). No significant differences were found between the groups for visual field and best-corrected visual acuity. No adverse effects were observed. Treatment with 9-cis β-carotene significantly increased retinal function in patients with RP under the tested conditions. The optimal therapeutic regimen will be determined in future, larger clinical trials. 9-cis β-Carotene may

  15. Retinitis pigmentosa and allied conditions today: a paradigm of translational research

    PubMed Central

    2010-01-01

    Monogenic human retinal dystrophies are a group of disorders characterized by progressive loss of photoreceptor cells leading to visual handicap. Retinitis pigmentosa is a type of retinal dystrophy where degeneration of rod photoreceptors occurs at the early stages. At present, there are no available effective therapies to maintain or improve vision in patients affected with retinitis pigmentosa, but post-genomic studies are allowing the development of potential therapeutic approaches. This review summarizes current knowledge on genes that have been identified to be responsible for retinitis pigmentosa, the involvement of these genes in the different forms of the disorder, the role of the proteins encoded by these genes in retinal function, the utility of genotyping, and current efforts to develop novel therapies. PMID:20519033

  16. Rod Photoreceptor Temporal Properties in Retinitis Pigmentosa

    PubMed Central

    Wen, Yuquan; Locke, Kirsten G.; Hood, Donald C.; Birch, David G.

    2011-01-01

    One of the characteristic signs of retinitis pigmentosa (RP) is the progressive loss of night vision. We have previously shown that the gain of rod photoreceptor activation is moderately reduced in some patients with RP, but this decrease in activation kinetics is not sufficient to account for the night blindness. Recently, single rod recording from animal models of RP showed rods under degeneration remain saturated for shorter periods than normal rods; i.e. are less able to sustain the rod photoresponse. Using paired-flash ERG, here we determine whether rod phototransduction inactivation parameters might also be abnormal in patients with RP. Inactivation parameters were derived from 13 subjects with normal vision, 16 patients with adRP, and 16 patients with autosomal recessive/isolate (rec/iso) RP. The adRP cases included 9 patients with rhodopsin mutations and 7 patients with peripherin/RDS mutations. The inactivation phase was derived using a double-flash paradigm, with a test flash of 2.7 log scot td-sec followed at varying intervals by a 4.2 log scot td-sec probe flash. Derived rod photoresponses to this just-saturating test flash in normal subjects exhibit a critical time to the initiation of recovery (Tsat) of 525±90 (SD) msec. The values of Tsat were 336±104 (SD) msec in patients with adRP (P<0.001) and 271±45 (SD) msec (P<0.001) in patients with rec/iso RP. When Tsat values were categorized by mutations, the values were 294±91 (SD) msec (P<0.001) for rhodopsin mutations, and 389±100 (SD) msec (p=0.01) for peripherin/RDS mutations. Overall, Tsat in patients with RP was significantly correlated with the amplitude of ISCEV standard rod response (r = 0.56; P < 0.001) and the gain of the activation phase of phototransduction (r=0.6, P<0.001). Tsat may be a useful marker for therapeutic efficacy in future clinical trials in RP. PMID:21219898

  17. The Role of Fundus Autofluorescence in Late-Onset Retinitis Pigmentosa (LORP) Diagnosis

    PubMed Central

    Lee, Tamara J.; Hwang, John C.; Chen, Royce W. S.; Lima, Luiz H.; Wang, Nan-Kai; Tosi, Joaquin; Freund, K. Bailey; Yannuzzi, Lawrence A.; Tsang, Stephen H.

    2015-01-01

    Purpose To demonstrate the utility and characteristics of fundus autofluorescence in late-onset retinitis pigmentosa. Methods Observational case series. Patients diagnosed with late-onset retinitis pigmentosa were identified retrospectively in an institutional setting. Twelve eyes of six patients were identified and medical records were reviewed. Results All patients presented with slowly progressive peripheral field loss and initial clinical examination revealed only subtle retinal changes. There was a notable lack of intraretinal pigment migration in all patients. Five out of six patients underwent magnetic resonance imaging of the brain to rule out intracranial processes and all were referred from another ophthalmologist for further evaluation. Fundus autofluorescence was ultimately employed in all patients and revealed more extensive retinal pathology than initially appreciated on clinical examination. Fundus autofluorescence directed the workup toward a retinal etiology in all cases and led to the eventual diagnosis of late-onset retinitis pigmentosa through electroretinogram testing. Conclusion Fundus autofluorescence may be a more sensitive marker for retinal pathology than stereo fundus biomicroscopy alone in late-onset retinitis pigmentosa. Early use of fundus autofluorescence imaging in the evaluation of patients with subtle retinal lesions and complaints of peripheral field loss may be an effective strategy for timely and cost-efficient diagnosis. PMID:23899229

  18. The role of fundus autofluorescence in late-onset retinitis pigmentosa (LORP) diagnosis.

    PubMed

    Lee, Tamara J; Hwang, John C; Chen, Royce W S; Lima, Luiz H; Wang, Nan-Kai; Tosi, Joaquin; Freund, K Bailey; Yannuzzi, Lawrence A; Tsang, Stephen H

    2014-09-01

    To demonstrate the utility and characteristics of fundus autofluorescence in late-onset retinitis pigmentosa. Observational case series. Patients diagnosed with late-onset retinitis pigmentosa were identified retrospectively in an institutional setting. Twelve eyes of six patients were identified and medical records were reviewed. All patients presented with slowly progressive peripheral field loss and initial clinical examination revealed only subtle retinal changes. There was a notable lack of intraretinal pigment migration in all patients. Five out of six patients underwent magnetic resonance imaging of the brain to rule out intracranial processes and all were referred from another ophthalmologist for further evaluation. Fundus autofluorescence was ultimately employed in all patients and revealed more extensive retinal pathology than initially appreciated on clinical examination. Fundus autofluorescence directed the workup toward a retinal etiology in all cases and led to the eventual diagnosis of late-onset retinitis pigmentosa through electroretinogram testing. Fundus autofluorescence may be a more sensitive marker for retinal pathology than stereo fundus biomicroscopy alone in late-onset retinitis pigmentosa. Early use of fundus autofluorescence imaging in the evaluation of patients with subtle retinal lesions and complaints of peripheral field loss may be an effective strategy for timely and cost-efficient diagnosis.

  19. Retinitis Pigmentosa: Genes and Disease Mechanisms

    PubMed Central

    Ferrari, Stefano; Di Iorio, Enzo; Barbaro, Vanessa; Ponzin, Diego; Sorrentino, Francesco S; Parmeggiani, Francesco

    2011-01-01

    Retinitis pigmentosa (RP) is a group of inherited disorders affecting 1 in 3000-7000 people and characterized by abnormalities of the photoreceptors (rods and cones) or the retinal pigment epithelium of the retina which lead to progressive visual loss. RP can be inherited in an autosomal dominant, autosomal recessive or X-linked manner. While usually limited to the eye, RP may also occur as part of a syndrome as in the Usher syndrome and Bardet-Biedl syndrome. Over 40 genes have been associated with RP so far, with the majority of them expressed in either the photoreceptors or the retinal pigment epithelium. The tremendous heterogeneity of the disease makes the genetics of RP complicated, thus rendering genotype-phenotype correlations not fully applicable yet. In addition to the multiplicity of mutations, in fact, different mutations in the same gene may cause different diseases. We will here review which genes are involved in the genesis of RP and how mutations can lead to retinal degeneration. In the future, a more thorough analysis of genetic and clinical data together with a better understanding of the genotype-phenotype correlation might allow to reveal important information with respect to the likelihood of disease development and choices of therapy. PMID:22131869

  20. ADIPOR1 is mutated in syndromic retinitis pigmentosa

    PubMed Central

    Xu, Mingchu; Eblimit, Aiden; Wang, Jing; Li, Jianli; Wang, Feng; Zhao, Li; Wang, Xia; Xiao, Ningna; Li, Yumei; Wong, Lee-Jun C.; Lewis, Richard A.; Chen, Rui

    2017-01-01

    Retinitis pigmentosa (RP) is a genetically heterogeneous retinal disorder. Despite the numerous genes associated with RP already identified, the genetic basis remains unknown in a substantial number of patients and families. In this study, we performed whole exome sequencing to investigate the molecular basis of a syndromic RP case which cannot be solved by mutations in known disease-causing genes. After applying a series of variant filtering strategies, we identified an apparently homozygous frameshift mutation, c.31delC (p.Q11Rfs*24) in the ADIPOR1 gene. The reported phenotypes of Adipor1-null mice contain retinal dystrophy, obesity and behavioral abnormalities, which highly mimic those in the syndromic RP patient. We further confirmed ADIPOR1 retina expression by immunohistochemistry. Our results established ADIPOR1 as a novel disease-causing gene for syndromic RP and highlight the importance of fatty acid transport in the retina. PMID:26662040

  1. Visual Discrimination Increase by Yellow Filters in Retinitis Pigmentosa.

    PubMed

    Cedrún-Sánchez, Juan E; Chamorro, Eva; Bonnin-Arias, Cristina; Aguirre-Vilacoro, Victoria; Castro, José J; Sánchez-Ramos, Celia

    2016-12-01

    The objective of this study was to evaluate, by halometry and under low illumination conditions, the effects of short-wavelength light absorbance filters on visual discrimination capacity in retinitis pigmentosa patients. This was an observational, prospective, analytic, and transversal study on 109 eyes of 57 retinitis pigmentosa patients with visual acuity better than 1.25 logMAR. Visual disturbance index (VDI) was determined using the software Halo 1.0, with and without the interposition of filters which absorb (totally or partially) short-wavelength light between 380 and 500 nm. A statistically significant reduction in the VDI values determined using filters which absorb short-wavelength light was observed (p < 0.0001). The established VDIs in patients with VA logMAR <0.4 were 0.30 ± 0.05 (95% CI, 0.26-0.36) for the lens alone, 0.20 ± 0.04 (95% CI, 0.16-0.24) with the filter that completely absorbs wavelengths shorter than 450 nm, and 0.24 ± 0.04 (95% CI, 0.20-0.28) with the filter that partially absorbs wavelengths shorter than 450 nm, which implies a 20 to 33% visual discrimination capacity increase. In addition, a decrease of VDI in at least one eye was observed in more than 90% of patients when using a filter. Short-wavelength light absorbance filters increase visual discrimination capacity under low illumination conditions in retinitis pigmentosa patients. Use of such filters constitutes a suitable method to improve visual quality related to intraocular light visual disturbances under low illumination conditions in this group of patients.

  2. Genetic characterization and disease mechanism of retinitis pigmentosa; current scenario.

    PubMed

    Ali, Muhammad Umar; Rahman, Muhammad Saif Ur; Cao, Jiang; Yuan, Ping Xi

    2017-08-01

    Retinitis pigmentosa is a group of genetically transmitted disorders affecting 1 in 3000-8000 individual people worldwide ultimately affecting the quality of life. Retinitis pigmentosa is characterized as a heterogeneous genetic disorder which leads by progressive devolution of the retina leading to a progressive visual loss. It can occur in syndromic (with Usher syndrome and Bardet-Biedl syndrome) as well as non-syndromic nature. The mode of inheritance can be X-linked, autosomal dominant or autosomal recessive manner. To date 58 genes have been reported to associate with retinitis pigmentosa most of them are either expressed in photoreceptors or the retinal pigment epithelium. This review focuses on the disease mechanisms and genetics of retinitis pigmentosa. As retinitis pigmentosa is tremendously heterogeneous disorder expressing a multiplicity of mutations; different variations in the same gene might induce different disorders. In recent years, latest technologies including whole-exome sequencing contributing effectively to uncover the hidden genesis of retinitis pigmentosa by reporting new genetic mutations. In future, these advancements will help in better understanding the genotype-phenotype correlations of disease and likely to develop new therapies.

  3. Dorzolamide Chlorhydrate Versus Acetazolamide in the Management of Chronic Macular Edema in Patients with Retinitis Pigmentosa: Description of Three Case Reports

    PubMed Central

    Pacella, Elena; Arrico, Loredana; Santamaria, Valentina; Turchetti, Paolo; Carbotti, Maria Rosaria; La Torre, Giuseppe; Pacella, Fernanda

    2014-01-01

    AIMS To assess the efficacy of topical dorzolamide for treating cystoid macular edema in patients with retinitis pigmentosa and minimize the secondary effects of maintenance therapy in patients with retinitis pigmentosa (RP) who present with chronic microcystic macular edema. METHODS To replace acetazolamide systemic treatment, with a topical treatment using 2% dorzolamide in three patients. The methods performed were OCT scan with a Spectralis HRA-OCT, for the measurement of macular thickness and morphology; best corrected visual acuity was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS), was assessed slit-lamp biomicroscopy, ocular tonometry, fundus biomiocrosopy, and color fundus photography. This therapeutic protocol has been applied and described in three patients. RESULTS In all three tested patients, following the administration of dorzolamide in eye drop, we observed a remarkable decrease in macular edema, almost comparable to that obtained with acetazolamide per os. CONCLUSION The study confirms the anti-edematogenic effect of topical dorzolamide in RP with recurring macular cysts, as this can have a favorable response with topical dorzolamide. In all the three examined patients, the instillation of topical dorzolamide caused a remarkable reduction in their macular edema, as highlighted on OCT. PMID:24932106

  4. CLINICAL PRESENTATIONS AND OUTCOMES OF RHEGMATOGENOUS RETINAL DETACHMENT IN RETINITIS PIGMENTOSA.

    PubMed

    Dave, Vivek P; Jalali, Subhadra; Nayaka, Ashraya; Pappuru, Rajeev R; Pathengay, Avinash; Das, Taraprasad

    2016-07-01

    To describe the clinical presentations and outcomes of rhegmatogenous retinal detachments (RRD) in eyes with retinitis pigmentosa. A retrospective review of all patients of retinitis pigmentosa with RRD from January 1990 to December 2013 at a tertiary eye care institute. Of total 28,622 patients of retinitis pigmentosa over a 23-year period, 17 eyes of 17 patients had RRD. Mean age at presentation was 34.53 ± 16.42 years (median 32 years). Median duration of decreased vision attributed to RRD was 6 months. Ten eyes (59%) had cataract and 3 eyes (18%) had history of cataract surgery. Thirteen eyes (76%) had inferior retinal detachment; 9 eyes (53%) had lattice with retinal holes; and 8 eyes (47%) had atrophic retinal holes. There were no horse-shoe tears, giant retinal tears, dialysis, and macular holes related RRD. Majority (82%) of retinal breaks were in the inferotemporal quadrant. Only 3 eyes (18%) had proliferative vitreoretinopathy at presentation. Twelve eyes at presentation had best-corrected visual acuity <20/200 and 6 eyes had only light perception. The macula was involved by the detachment in all cases. Mean preoperative visual acuity was 1.4 ± 0.88 logarithm of the minimum angle of resolution (median 1.3, range 3-0.1; 20/502). Surgery was not advised in 6 eyes (35% patients); 5 eyes (30%) underwent scleral buckling and 6 eyes (35%) underwent vitrectomy. Median follow-up was 5 months. Reattachment rate at last follow-up was 91% (15 eyes). Mean postoperative best-corrected visual acuity recorded was 1.06 ± 0.8 (median 1, range 3-0.1; 20/229) (P = 0.15). Eight eyes at last visit had best-corrected visual acuity <20/200. Of the 11 eyes operated, 4 improved in vision and 7 retained the preoperative vision. The incidence of RRD in retinitis pigmentosa is very low. Presentation, although delayed, is at a younger age. Horse-shoe tears and proliferative vitreoretinopathy are uncommon; cataract is a common coexisting pathology. Surgical reattachment rates

  5. Spectral-Domain Optical Coherence Tomography Measures of Outer Segment Layer Progression in Patients With X-Linked Retinitis Pigmentosa

    PubMed Central

    Birch, David G.; Locke, Kirsten G.; Wen, Yuquan; Locke, Kelly I.; Hoffman, Dennis R.; Hood, Donald C.

    2014-01-01

    IMPORTANCE Determining the annual rate of change in the width of the inner segment ellipsoid zone (EZ; ie, inner/outer segment border) in the context of short-term variability should allow us to better understand the value of this measure for future treatment trials in X-linked retinitis pigmentosa (XLRP). OBJECTIVES To identify the width of the central region showing an EZ and to determine the short-term repeat variability and the annual rate of change in the width of the EZ from spectral-domain optical coherence tomography (SD-OCT) measures in RP. DESIGN Patients with recessive or simplex RP (age range, 8–65 years; mean age, 40.5 years) underwent scanning twice on the same day to evaluate test-retest variability. Patients with XLRP (age range, 8–27 years; mean age, 15.2 years) from a larger group participating in an ongoing double-blind treatment trial (docosahexaenoic acid vs placebo; clinicaltrials.gov NCT00100230) underwent spectral-domain optical coherence tomography line scanning across the horizontal meridian at 3 yearly intervals. SETTING Research center specializing in medical retina. PARTICIPANTS Forty-eight patients with RP, including 20 with recessive or simplex RP and 28 with XLRP, and 23 healthy control subjects. MAIN OUTCOME AND MEASURE Widths of the EZ calculated and compared among the 3 annual visits. RESULTS Test-retest differences were normally distributed, and the magnitude of the difference was independent of mean EZ width. The mean (SD) for test-retest differences in EZ width was 0.08° (0.22°) (range, −0.30° to 0.60°). Thus, 95%of all test-retest differences fall within ±0.43° (124 µm). Of the 28 patients with XLRP, 27 showed a significant decrease in EZ width after 2 years. Patients with XLRP showed a mean annual decrease in EZ width of 0.86° (248 µm, or 7%). CONCLUSIONS AND RELEVANCE The mean rate of decline in EZ width (7%) translates into a mean rate of change of 13%for the equivalent area of functioning retina. This rate

  6. Spectral-domain optical coherence tomography measures of outer segment layer progression in patients with X-linked retinitis pigmentosa.

    PubMed

    Birch, David G; Locke, Kirsten G; Wen, Yuquan; Locke, Kelly I; Hoffman, Dennis R; Hood, Donald C

    2013-09-01

    Determining the annual rate of change in the width of the inner segment ellipsoid zone (EZ; ie, inner/outer segment border) in the context of short-term variability should allow us to better understand the value of this measure for future treatment trials in X-linked retinitis pigmentosa (XLRP). To identify the width of the central region showing an EZ and to determine the short-term repeat variability and the annual rate of change in the width of the EZ from spectral-domain optical coherence tomography (SD-OCT) measures in RP. Patients with recessive or simplex RP (age range, 8-65 years; mean age, 40.5 years) underwent scanning twice on the same day to evaluate test-retest variability. Patients with XLRP (age range, 8-27 years; mean age, 15.2 years) from a larger group participating in an ongoing double-blind treatment trial (docosahexaenoic acid vs placebo; clinicaltrials.gov NCT00100230) underwent spectral-domain optical coherence tomography line scanning across the horizontal meridian at 3 yearly intervals. Research center specializing in medical retina. Forty-eight patients with RP, including 20 with recessive or simplex RP and 28 with XLRP, and 23 healthy control subjects. Widths of the EZ calculated and compared among the 3 annual visits. Test-retest differences were normally distributed, and the magnitude of the difference was independent of mean EZ width. The mean (SD) for test-retest differences in EZ width was 0.08° (0.22°) (range, -0.30° to 0.60°). Thus, 95% of all test-retest differences fall within ± 0.43° (124 μm). Of the 28 patients with XLRP, 27 showed a significant decrease in EZ width after 2 years. Patients with XLRP showed a mean annual decrease in EZ width of 0.86° (248 μm, or 7%). The mean rate of decline in EZ width (7%) translates into a mean rate of change of 13% for the equivalent area of functioning retina. This rate of change is consistent with that reported for visual fields and full-field electroretinograms. Unlike visual

  7. Unilateral retinitis pigmentosa and cone-rod dystrophy

    PubMed Central

    Farrell, Donald F

    2009-01-01

    Purpose: The purpose of this paper is to report 14 new cases of unilateral retinitis pigmentosa and three new cases of cone-rod dystrophy and to compare the similarities and dissimilarities to those found in the bilateral forms of these disorders. Methods: A total of 272 cases of retinitis pigmentosa and 167 cases of cone-rod dystrophy were studied by corneal full field electroretinograms and electrooculograms. The student t-test was used to compare categories. Results: The percentage of familial and nonfamilial cases was the same for the bilateral and unilateral forms of the disease. In our series, unilateral retinitis pigmentosa makes up approximately 5% of the total population of retinitis pigmentosa, while unilateral cone-rod dystrophy makes up only about 2% of the total. In the familial forms of unilateral retinitis pigmentosa the most common inheritance pattern was autosomal dominant and all affected relatives had bilateral disease. Conclusion: Unilateral retinitis pigmentosa and cone-rod dystrophy appear to be directly related to the more common bilateral forms of these disorders. The genetic mechanisms which account for asymmetric disorders are not currently understood. It may be a different unidentified mutation at a single loci or it is possible that nonlinked mutations in multiple loci account for this unusual disorder. PMID:19668577

  8. Macular pigment optical density is related to serum lutein in retinitis pigmentosa

    USDA-ARS?s Scientific Manuscript database

    Purpose: To determine whether macular pigment optical density (MPOD) is related to the degree of cystoid macular edema (CME) in patients with retinitis pigmentosa. Methods: We measured MPOD with heterochromatic flicker photometry and central foveal retinal thickness with optical coherence tomography...

  9. [Clinical observation of Erlong Xizhu acupuncture for retinitis pigmentosa].

    PubMed

    Zhao, Yaodong; Han, Douying

    2015-07-01

    To explore the clinical effect of Erlong Xizhu acupuncture for retinitis pigmentosa. Methods Sixty patients with retinitis pigmentosa were randomly divided into an Erlong Xizhu acupuncture group and a conventional acupuncture group, 30 cases in each one. In the conventional acupuncture group, Tongziliao (GB 1), Sizhukong (TE 23), Taiyang (EX-HN 5) were acupunctured as the main acupoints by uniform reinforcing-reducing manipulation; acupoints based on syndrome differentiation were coordinated by acupuncture manipulation of reinforcing deficiency and reducing excess. The treatment in the Erlong Xizhu acupuncture group was the same as that in the conventional group, except acupuncture manipulation at the main acupoints replaced by Erlong Xizhu acupuncture. In the two groups, treatment was given once a day, 10 days as one session and there were 2 days at the interval between sessions. The change of the vision and visual field and the efficacy were observed after 3 sessions in the two groups. The total effective rate on enhancing the vision of patients in the Erlong Xizhu acupuncture group was 93. 10% (54/58), which was superior to 81. 36% (48/59) in the conventional acupuncture group (P<0. 01). And the effective rate on improving the visual field was 91. 38% (53/58) in the Erlong Xizhu acupuncture group, which was better than 83. 05% (49/59) in the conventional acupuncture group (P<0. 01). On the comprehensive effect, the effective rate was 90. 00% (27/30) in the Erlong Xizhu acupuncture group, which was better than 63. 34% (19/30) in the conventional acupuncture group (P<0. 05). The clinical effect of Erlong Xizhu acupuncture is superior to that of conventional acupuncture for retinitis pigmentosa and it is worthy of promoting.

  10. [Fourier analysis of macular local electroretinogram in retinitis pigmentosa].

    PubMed

    Wu, X; Zhang, X; Zhu, P

    2000-08-01

    To understand the sites of macular dysfunction in retinitis pigmentosa (RP) by evaluating local electroretinogram (LERG) and further evaluating fundamental and second harmonic components. LERG were recorded in 98 eyes of 49 patients to a flickered sinusoid of 31Hz and 10Hz with a hand-held stimulator with direct visualization of the fundus through dilated pupils. Compared to controls, the patients showed losses of both fundamental and second harmonic amplitudes. The abnormality ratios of fundamental amplitudes in RP affected time < 5 years, 5 - 15 years, 15 - 25 years and > 25 years were 54%, 64%, 83% and 92% respectively; and the abnormality ratios of second harmonic amplitudes were 18%, 36%, 58% and 75% respectively. The fundamental-second harmonic ratio was much more higher in the autosomal recessive and sporadic patients than in the autosomal dominant patients (P < 0.01). On average, the fundamental-second harmonic ratio in the patients tended to increase with age. The results suggest that in the retinitis pigmentosa, both receptoral and postreceptoral sites contribute to macular dysfunction. The level of macular dysfunction in different types of hereditary patients is different. It would be of clinical value to obtain a fundamental-second harmonic ratio in order to assess the disturbance in different sites of macular.

  11. Genes and Mutations Causing Autosomal Dominant Retinitis Pigmentosa

    PubMed Central

    Daiger, Stephen P.; Bowne, Sara J.; Sullivan, Lori S.

    2015-01-01

    Retinitis pigmentosa (RP) has a prevalence of approximately one in 4000; 25%–30% of these cases are autosomal dominant retinitis pigmentosa (adRP). Like other forms of inherited retinal disease, adRP is exceptionally heterogeneous. Mutations in more than 25 genes are known to cause adRP, more than 1000 mutations have been reported in these genes, clinical findings are highly variable, and there is considerable overlap with other types of inherited disease. Currently, it is possible to detect disease-causing mutations in 50%–75% of adRP families in select populations. Genetic diagnosis of adRP has advantages over other forms of RP because segregation of disease in families is a useful tool for identifying and confirming potentially pathogenic variants, but there are disadvantages too. In addition to identifying the cause of disease in the remaining 25% of adRP families, a central challenge is reconciling clinical diagnosis, family history, and molecular findings in patients and families. PMID:25304133

  12. Mistrafficking of prenylated proteins causes retinitis pigmentosa 2

    PubMed Central

    Zhang, Houbin; Hanke-Gogokhia, Christin; Jiang, Li; Li, Xiaobo; Wang, Pu; Gerstner, Cecilia D.; Frederick, Jeanne M.; Yang, Zhenglin; Baehr, Wolfgang

    2015-01-01

    The retinitis pigmentosa 2 polypeptide (RP2) functions as a GTPase-activating protein (GAP) for ARL3 (Arf-like protein 3), a small GTPase. ARL3 is an effector of phosphodiesterase 6 Δ (PDE6D), a prenyl-binding protein and chaperone of prenylated protein in photoreceptors. Mutations in the human RP2 gene cause X-linked retinitis pigmentosa (XLRP) and cone-rod dystrophy (XL-CORD). To study mechanisms causing XLRP, we generated an RP2 knockout mouse. The Rp2h−/− mice exhibited a slowly progressing rod-cone dystrophy simulating the human disease. Rp2h−/− scotopic a-wave and photopic b-wave amplitudes declined at 1 mo of age and continued to decline over the next 6 mo. Prenylated PDE6 subunits and G-protein coupled receptor kinase 1 (GRK1) were unable to traffic effectively to the Rp2h−/− outer segments. Mechanistically, absence of RP2 GAP activity increases ARL3-GTP levels, forcing PDE6D to assume a predominantly “closed” conformation that impedes binding of lipids. Lack of interaction disrupts trafficking of PDE6 and GRK1 to their destination, the photoreceptor outer segments. We propose that hyperactivity of ARL3-GTP in RP2 knockout mice and human patients with RP2 null alleles leads to XLRP resembling recessive rod-cone dystrophy.—Zhang, H., Hanke-Gogokhia, C., Jiang, L., Li, X., Wang, P., Gerstner, C. D., Frederick, J. M., Yang, Z., Baehr, W. Mistrafficking of prenylated proteins causes retinitis pigmentosa 2. PMID:25422369

  13. Retinitis pigmentosa and macular degeneration in a patient with ataxia with isolated vitamin E deficiency with a novel c.717 del C mutation in the TTPA gene.

    PubMed

    Iwasa, Kazuo; Shima, Keisuke; Komai, Kiyonobu; Nishida, Yoichiro; Yokota, Takanori; Yamada, Masahito

    2014-10-15

    Ataxia with isolated vitamin E deficiency (AVED) is a neurodegenerative disease caused by a mutation in the α-tocopherol transfer protein gene (TTPA). The clinical features of the disease resemble Friedreich's ataxia. However, AVED is associated with low plasma vitamin E levels, which results in compromised antioxidant function. Dysregulation of this lipid-soluble antioxidant vitamin plays a major role in the neurodegeneration observed in AVED. Some AVED patients experience decreased visual acuity. Retinitis pigmentosa is thought to be the main cause of this visual impairment. Although antioxidant levels are important for the prevention of macular degeneration, there have been no reports of macular degeneration in AVED. Here, we describe a patient with AVED with progressive macular degeneration, who carried a novel truncating mutation-c.717 del C (p.D239EfsX25)-in exon 5 of the TTPA gene. These findings suggest that this newly identified mutation results in severely low serum vitamin E levels, which may be associated with the development of retinitis pigmentosa and macular degeneration.

  14. A Qualitative Self-Study of Retinitis Pigmentosa

    ERIC Educational Resources Information Center

    Fourie, Robert James

    2007-01-01

    Retinitis Pigmentosa (RP) is a retinal degenerative disease causing progressive blindness. Most research on RP is biomedical, and mostly from an observer perspective, therefore poorly reflecting the lived experience of having RP. Accordingly, the researcher conducted a retrospective qualitative self-study, to analyze reflections on his own…

  15. A Qualitative Self-Study of Retinitis Pigmentosa

    ERIC Educational Resources Information Center

    Fourie, Robert James

    2007-01-01

    Retinitis Pigmentosa (RP) is a retinal degenerative disease causing progressive blindness. Most research on RP is biomedical, and mostly from an observer perspective, therefore poorly reflecting the lived experience of having RP. Accordingly, the researcher conducted a retrospective qualitative self-study, to analyze reflections on his own…

  16. Retinitis pigmentosa associated with peripheral sea fan neovascularization.

    PubMed

    Kadayifçilar, S; Eldem, B; Kiratli, H

    2000-10-01

    To describe a case with retinitis pigmentosa associated with sea fan type retinal neovascularization. Complete ocular examination including fluorescein angiography was performed in a 9-year-old girl. Ophthalmoscopically, in addition to arteriolar narrowing and bone corpuscular pigmentation of both retinae, a vascular lesion with surrounding intraretinal exudation was noted in the upper equatorial region of the right eye. On fluorescein angiography, the lesion stained in the form of a sea fan neovascularization. Sea fan type of neovascularization can be seen in association with retinitis pigmentosa. Fluorescein angiography is important in identifying the exact nature of such a lesion.

  17. Progress in gene targeting and gene therapy for retinitis pigmentosa

    SciTech Connect

    Farrar, G.J.; Humphries, M.M.; Erven, A.

    1994-09-01

    Previously, we localized disease genes involved in retinitis pigmentosa (RP), an inherited retinal degeneration, close to the rhodopsin and peripherin genes on 3q and 6p. Subsequently, we and others identified mutations in these genes in RP patients. Currently animal models for human retinopathies are being generated using gene targeting by homologous recombination in embryonic stem (ES) cells. Genomic clones for retinal genes including rhodopsin and peripherin have been obtained from a phage library carrying mouse DNA isogenic with the ES cell line (CC1.2). The peripherin clone has been sequenced to establish the genomic structure of the mouse gene. Targeting vectors for rhodopsin and peripherin including a neomycin cassette for positive selection and thymidine kinase genes enabling selection against random intergrants are under construction. Progress in vector construction will be presented. Simultaneously we are developing systems for delivery of gene therapies to retinal tissues utilizing replication-deficient adenovirus (Ad5). Efficacy of infection subsequent to various methods of intraocular injection and with varying viral titers is being assayed using an adenovirus construct containing a CMV promoter LacZ fusion as reporter and the range of tissues infected and the level of duration of LacZ expression monitored. Viral constructs with the LacZ reporter gene under the control of retinal specific promoters such as rhodopsin and IRBP cloned into pXCJL.1 are under construction. An update on developments in photoreceptor cell-directed expression of virally delivered genes will be presented.

  18. Mistrafficking of prenylated proteins causes retinitis pigmentosa 2.

    PubMed

    Zhang, Houbin; Hanke-Gogokhia, Christin; Jiang, Li; Li, Xiaobo; Wang, Pu; Gerstner, Cecilia D; Frederick, Jeanne M; Yang, Zhenglin; Baehr, Wolfgang

    2015-03-01

    The retinitis pigmentosa 2 polypeptide (RP2) functions as a GTPase-activating protein (GAP) for ARL3 (Arf-like protein 3), a small GTPase. ARL3 is an effector of phosphodiesterase 6 Δ (PDE6D), a prenyl-binding protein and chaperone of prenylated protein in photoreceptors. Mutations in the human RP2 gene cause X-linked retinitis pigmentosa (XLRP) and cone-rod dystrophy (XL-CORD). To study mechanisms causing XLRP, we generated an RP2 knockout mouse. The Rp2h(-/-) mice exhibited a slowly progressing rod-cone dystrophy simulating the human disease. Rp2h(-/-) scotopic a-wave and photopic b-wave amplitudes declined at 1 mo of age and continued to decline over the next 6 mo. Prenylated PDE6 subunits and G-protein coupled receptor kinase 1 (GRK1) were unable to traffic effectively to the Rp2h(-/-) outer segments. Mechanistically, absence of RP2 GAP activity increases ARL3-GTP levels, forcing PDE6D to assume a predominantly "closed" conformation that impedes binding of lipids. Lack of interaction disrupts trafficking of PDE6 and GRK1 to their destination, the photoreceptor outer segments. We propose that hyperactivity of ARL3-GTP in RP2 knockout mice and human patients with RP2 null alleles leads to XLRP resembling recessive rod-cone dystrophy. © FASEB.

  19. Eye Motility Alterations in Retinitis Pigmentosa.

    PubMed

    Migliorini, Raffaele; Comberiati, Anna Maria; Galeoto, Giovanni; Fratipietro, Manuela; Arrico, Loredana

    2015-01-01

    Purpose. We evaluated a sample of individuals with retinitis pigmentosa (RP) with the aim of assessing the presence or absence of ocular motility (OM) disorders. Materials and Methods. We included 23 out of the 25 individuals from the sample (9 females and 14 males) with an average visual acuity of 6/10. Results. The cover test about the vertical deviation in near distance showed an r/l in 3.45% and an l/r in 6.9%. The assessment of OM showed that 39.1% of the sample had a severe hyperfunction of the IO of the right eye and a severe hyperfunction (34.5%) of the SO of the left eye; 21.8% had a moderate hypofunction of right SO with a moderate percentage of hypofunction of 17.5% for the SO of the left eye; 30.5%, however, showed a serious hypofunction of the SR of both eyes; 21.7% of the sample showed a hyperfunction in both eyes of the IR. Conclusion. This alteration, however, is not attributable to either a high refractive defect (medium-low myopia: -1 diopter ±3 SD) or to a severely impaired binocular vision (visual acuity, motor fusion, and stereopsis are normal or within a range of values commonly accepted). Therefore, the disorders of OM lead to a genetic origin.

  20. Hereditary and Clinical Features of Retinitis Pigmentosa in Koreans

    PubMed Central

    Lee, Sun Ho; Seo, Jong Mo; Moon, Sang Woong; Moon, Jun Woong; Kim, Sang Jin; Chung, Hum

    2010-01-01

    There has been no report about hereditary and clinical features of retinitis pigmentosa (RP) in Koreans. To evaluate these, data were collected from 365 RP patients including age, gender, visual acuity (VA), spherical equivalent (SE) of refractive errors, funduscopic findings, color vision test, visual field score (VFS) obtained from Goldmann perimetry, and the inheritance patterns from pedigrees. Simplex RP was the most common inheritance pattern (61.9%); followed by autosomal recessive RP (17.3%), autosomal dominant RP (12.1%) and X-linked recessive RP (8.8%). Myopia was the most common refractive errors (77.5%) including 16.1% of high myopia. The most common cataract type was posterior subcapsular cataract (25.8%). Observed retinal findings included changes of retinal pigment epithelium (88.8%), bony spicule-like pigmentation (79.7%), attenuation of retinal vessel (76.2%), waxy disc pallor (12.6%), golden ring around optic disc (2.2%), epiretinal membrane (0.8%) and cystoid macular edema (0.5%). Corrected VA and refractive errors did not show any significant difference between the inheritance patterns. VFS was significantly worse in autosomal recessive RP than in autosomal dominant RP. Color vision defect was noted in 66.1% on Hardy-Rand-Rittlers color vision test. In conclusion, Korean RP patients have the indigenous hereditary and clinical features as well as the ordinary ones. PMID:20514315

  1. Hereditary and clinical features of retinitis pigmentosa in Koreans.

    PubMed

    Lee, Sun Ho; Yu, Hyeong Gon; Seo, Jong Mo; Moon, Sang Woong; Moon, Jun Woong; Kim, Sang Jin; Chung, Hum

    2010-06-01

    There has been no report about hereditary and clinical features of retinitis pigmentosa (RP) in Koreans. To evaluate these, data were collected from 365 RP patients including age, gender, visual acuity (VA), spherical equivalent (SE) of refractive errors, funduscopic findings, color vision test, visual field score (VFS) obtained from Goldmann perimetry, and the inheritance patterns from pedigrees. Simplex RP was the most common inheritance pattern (61.9%); followed by autosomal recessive RP (17.3%), autosomal dominant RP (12.1%) and X-linked recessive RP (8.8%). Myopia was the most common refractive errors (77.5%) including 16.1% of high myopia. The most common cataract type was posterior subcapsular cataract (25.8%). Observed retinal findings included changes of retinal pigment epithelium (88.8%), bony spicule-like pigmentation (79.7%), attenuation of retinal vessel (76.2%), waxy disc pallor (12.6%), golden ring around optic disc (2.2%), epiretinal membrane (0.8%) and cystoid macular edema (0.5%). Corrected VA and refractive errors did not show any significant difference between the inheritance patterns. VFS was significantly worse in autosomal recessive RP than in autosomal dominant RP. Color vision defect was noted in 66.1% on Hardy-Rand-Rittlers color vision test. In conclusion, Korean RP patients have the indigenous hereditary and clinical features as well as the ordinary ones.

  2. Unilateral retinitis pigmentosa: a proposal of genetic pathogenic mechanisms.

    PubMed

    Marsiglia, Marcela; Duncker, Tobias; Peiretti, Enrico; Brodie, Scott E; Tsang, Stephen H

    2012-01-01

    To investigate and integrate anatomic and physiologic findings from a group of patients who present retinitis pigmentosa affecting just one eye and use this information to propose mechanisms of disease pathogenesis. This prospective cross-sectional study examined 5 patients, all female, from 8 to 60 years old. The study was conducted in 4 university hospitals. The patients were selected according to the characteristics of ocular involvement, notably unilateral presentation of similar anatomic and functional abnormalities. Full-field electroretinogram, fundus photography, fundus autofluorescence, infrared imaging, optical coherence tomography, and genetic testing were performed. Full-field electroretinogram showed unilateral decrease in amplitude and increase in implicit time; autofluorescence showed unilateral areas of decreased intensity. The USH2AW4149R mutation was confirmed in one patient. Imaging and functional testing are important in elucidating the unilateral pattern of the disease and in monitoring these individuals. Mosaicism or somatic mutation may cause unilateral genetic disease presentation.

  3. Unilateral retinitis pigmentosa: a proposal of genetic pathogenic mechanisms

    PubMed Central

    Marsiglia, Marcela; Duncker, Tobias; Peiretti, Enrico; Brodie, Scott E.; Tsang, Stephen H.

    2013-01-01

    Purpose To investigate and integrate anatomic and physiologic findings from a group of patients who present retinitis pigmentosa affecting just one eye and use this information to propose mechanisms of disease pathogenesis. Methods This prospective cross-sectional study examined 5 patients, all female, from 8 to 60 years old. The study was conducted in 4 university hospitals. The patients were selected according to the characteristics of ocular involvement, notably unilateral presentation of similar anatomic and functional abnormalities. Full-field electroretinogram, fundus photography, fundus autofluorescence, infrared imaging, optical coherence tomography, and genetic testing were performed. Results Full-field electroretinogram showed unilateral decrease in amplitude and increase in implicit time; autofluorescence showed unilateral areas of decreased intensity. The USH2AW4149R mutation was confirmed in one patient. Conclusions Imaging and functional testing are important in elucidating the unilateral pattern of the disease and in monitoring these individuals. Mosaicism or somatic mutation may cause unilateral genetic disease presentation. PMID:22139616

  4. The Relationship of Macular Pigment Optical Density to Serum Lutein in Retinitis Pigmentosa

    PubMed Central

    Johnson, Elizabeth J.; Berson, Eliot L.

    2010-01-01

    Purpose. To determine whether macular pigment optical density (MPOD) is related to serum lutein or serum zeaxanthin in patients with retinitis pigmentosa. Methods. The authors measured MPOD with heterochromatic flicker photometry, serum lutein and serum zeaxanthin by high performance liquid chromatography, and central foveal retinal thickness by optical coherence tomography (OCT) in 176 patients (age range, 18–68 years) with typical forms of retinitis pigmentosa; 37 (21%) of these patients had cystoid macular edema (CME) by OCT. The authors performed multiple regression analysis with MPOD as the dependent variable and with loge serum lutein and loge serum zeaxanthin as independent variables adjusting for age, sex, iris color, central foveal retinal thickness, and, in some analyses, serum total cholesterol. Results. MPOD increased with increasing serum lutein (P = 0.0017) and decreased with increasing serum total cholesterol (P = 0.0025) but was unrelated to serum zeaxanthin. MPOD was higher in patients with brown irides than in patients with lighter irides (P = 0.014) and was nonmonotonically related to central foveal retinal thickness (P < 0.0001), being lower in eyes with more photoreceptor cell loss and in eyes with moderate to marked CME. Conclusions. MPOD is independently related to serum lutein, serum total cholesterol, iris color, and central foveal retinal thickness in patients with retinitis pigmentosa. PMID:19797209

  5. Retinitis pigmentosa sine pigmenti. Debut with macular oedema.

    PubMed

    de la Mata Pérez, G; Ruiz-Moreno, O; Fernández-Pérez, S; Torrón Fernández-Blanco, C; Pablo-Júlvez, L

    2014-09-01

    A 25-year-old woman, with metamorphopsia in her left eye of one year onset. The examination revealed a bilateral cystoid macular oedema (CME) and vascular attenuation. We describe the diagnostic tests, as well as differential diagnosis and treatment response with carbonic anhydrase inhibitors. The retinitis pigmentosa sine pigment is a subtype of atypical retinitis pigmentosa characterised by the absence of pigment deposits. The night blindness is milder, and perimetric and electroretinographic impairment is lower. CME is an important cause of central vision loss, and responds to anhydrase carbonic inhibitors. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  6. Evidence for further genetic heterogeneity in autosomal dominant retinitis pigmentosa

    SciTech Connect

    Kumar-Singh, R.; Kenna, P.F.; Farrar, G.J.; Humphries, P. )

    1993-01-01

    We have investigated the possible involvement of further genetic heterogeneity in autosomal dominant retinitis pigmentosa using a previously unreported large Irish family with the disease. We have utilized polymorphic microsatellite markers to exclude the disease gene segregating in this family from 3q, 6p, and the pericentric region of 8, that is, each of the three chromosomal regions to which adRP loci are known to map. Hence, we provide definitive evidence for the involvement of a fourth locus in autosomal dominant retinitis pigmentosa. 25 refs., 2 figs.

  7. RITONAVIR-ASSOCIATED TOXICITY MIMICKING RETINITIS PIGMENTOSA IN AN HIV-INFECTED PATIENT ON HIGHLY ACTIVE ANTIRETROVIRAL THERAPY.

    PubMed

    Papavasileiou, Evangelia; Younis, Saad; Zygoura, Vasiliki; Quijano, Claudia; Jackson, Timothy L

    2017-01-01

    To report ritonavir-associated retinal pigment epithelium toxicity in a patient infected with the HIV on highly active antiretroviral therapy including ritonavir. Retrospective single case report. The authors describe a case of gradual onset of blurry vision in both eyes in an HIV-positive male. Visual acuity, clinical examination findings, and functional testing (electroretinogram and Goldmann perimetry) were reviewed. Diagnostic imaging, including fundus photography, spectral domain optical coherence tomography, fluorescein angiography, and fundus autofluorescence were assessed. 59-year-old HIV-infected male, treated with ritonavir for eight years, presented with a history of decreased night vision and peripheral field loss. Ophthalmologic examination confirmed the diagnosis of retinal toxicity. Goldmann perimetry showed areas of central and para-central scotomas. Electroretinograms demonstrated mild to moderate photoreceptor dysfunction. Fundus examination revealed a diffuse pattern of retinal pigment epithelium mottling in both eyes. Spectral domain optical coherence tomography confirmed the presence of choroidal thinning, whereas fundus autofluorescence showed mottled hypoautofluorescence. Although ritonavir-associated retinal toxicity is clinically uncommon, the clinical features of our findings support this diagnosis. Consideration of highly active antiretroviral therapy-associated retinal toxicity should be given to the differential diagnosis in HIV-positive patients with retinopathy of unclear etiology. This report also highlights the need for constant monitoring of patients using the ritonavir for early detection of possible retinal toxicity.

  8. Detection of retinitis pigmentosa by differential interference contrast microscopy.

    PubMed

    Oh, Juyeong; Kim, Seok Hwan; Kim, Yu Jeong; Lee, Hyunho; Cho, Joon Hyong; Cho, Young Ho; Kim, Chul-Ki; Lee, Taik Jin; Lee, Seok; Park, Ki Ho; Yu, Hyeong Gon; Lee, Hyuk-Jae; Jun, Seong Chan; Kim, Jae Hun

    2014-01-01

    Differential interference contrast microscopy is designed to image unstained and transparent specimens by enhancing the contrast resulting from the Nomarski prism-effected optical path difference. Retinitis pigmentosa, one of the most common inherited retinal diseases, is characterized by progressive loss of photoreceptors. In this study, Differential interference contrast microscopy was evaluated as a new and simple application for observation of the retinal photoreceptor layer and retinitis pigmentosa diagnostics and monitoring. Retinal tissues of Royal College of Surgeons rats and retinal-degeneration mice, both well-established animal models for the disease, were prepared as flatmounts and histological sections representing different elapsed times since the occurrence of the disease. Under the microscopy, the retinal flatmounts showed that the mosaic pattern of the photoreceptor layer was irregular and partly collapsed at the early stage of retinitis pigmentosa, and, by the advanced stage, amorphous. The histological sections, similarly, showed thinning of the photoreceptor layer at the early stage and loss of the outer nuclear layer by the advanced stage. To count and compare the number of photoreceptors in the normal and early-retinitis pigmentosa-stage tissues, an automated cell-counting program designed with MATLAB, a numerical computing language, using a morphological reconstruction method, was applied to the differential interference contrast microscopic images. The number of cells significantly decreased, on average, from 282 to 143 cells for the Royal College of Surgeons rats and from 255 to 170 for the retinal-degeneration mouse. We successfully demonstrated the potential of the differential interference contrast microscopy technique's application to the diagnosis and monitoring of RP.

  9. Optical Coherence Tomography Angiography to Estimate Retinal Blood Flow in Eyes with Retinitis Pigmentosa.

    PubMed

    Sugahara, Masako; Miyata, Manabu; Ishihara, Kenji; Gotoh, Norimoto; Morooka, Satoshi; Ogino, Ken; Hasegawa, Tomoko; Hirashima, Takako; Yoshikawa, Munemitsu; Hata, Masayuki; Muraoka, Yuki; Ooto, Sotaro; Yamashiro, Kenji; Yoshimura, Nagahisa

    2017-04-13

    Ophthalmologists sometimes face difficulties in identifying the origin of visual acuity (VA) loss in a retinitis pigmentosa (RP) patient, particularly before cataract surgery: cataract or the retinal disease state. Therefore, it is important to identify the significant factors correlating with VA. Nowadays, retinal blood flow in superficial and deep layers can be estimated non-invasively using optical coherence tomography angiography (OCTA). We estimated blood flow per retinal layer by using OCTA; investigated the correlation between VA and other parameters including blood flow and retinal thickness; and identified the most associated factor with VA in patients with RP. OCTA images in 68 of consecutive 110 Japanese RP patients were analysable (analysable RP group). Thirty-two age- and axial length-matched healthy eyes (control group) were studied. In the analysable RP group, the parafoveal flow density in superficial and deep layers was 47.0 ± 4.9% and 52.4 ± 5.5%, respectively, which was significantly lower than that in controls. Using multivariate analysis, we found that the parafoveal flow density in the deep layer and superficial foveal avascular area were the factors associated with VA. Non-invasive estimation of retinal blood flow per retinal layer using OCTA is useful for predicting VA in RP patients.

  10. Association between missense mutations in the BBS2 gene and nonsyndromic retinitis pigmentosa.

    PubMed

    Shevach, Elia; Ali, Manir; Mizrahi-Meissonnier, Liliana; McKibbin, Martin; El-Asrag, Mohammed; Watson, Christopher M; Inglehearn, Chris F; Ben-Yosef, Tamar; Blumenfeld, Anat; Jalas, Chaim; Banin, Eyal; Sharon, Dror

    2015-03-01

    A large number of genes can cause inherited retinal degenerations when mutated. It is important to identify the cause of disease for a better disease prognosis and a possible gene-specific therapeutic intervention. To identify the cause of disease in families with nonsyndromic retinitis pigmentosa. Patients and family members were recruited for the study and underwent clinical evaluation and genetic analyses. Identification of sequence variants in genes using next-generation sequencing. We performed exome sequencing for 4 families, which was followed by Sanger sequencing of the identified mutations in 120 ethnicity-matched patients. In total, we identified 4 BBS2 missense mutations that cause nonsyndromic retinitis pigmentosa. Three siblings of Moroccan Jewish ancestry were compound heterozygotes for p.A33D and p.P134R, and 6 patients belonging to 4 families of Ashkenazi Jewish ancestry were homozygous for either p.D104A or p.R632P, or compound heterozygous for these 2 mutations. The mutations cosegregated with retinitis pigmentosa in the studied families, and the affected amino acid residues are evolutionarily conserved. Our study shows that BBS2 mutations can cause nonsyndromic retinitis pigmentosa and highlights yet another candidate for this genetically heterogeneous condition.

  11. Increased aqueous flare is associated with thickening of inner retinal layers in eyes with retinitis pigmentosa

    PubMed Central

    Nagasaka, Yosuke; Ito, Yasuki; Ueno, Shinji; Terasaki, Hiroko

    2016-01-01

    Retinitis pigmentosa(RP) is a hereditary retinal disease that causes photoreceptor, outer retinal, degeneration. Although the pathogenesis is still unclear, there have been numerous reports regarding inner retinal changes in RP eyes. The aim of this study is to retrospectively evaluate the changes in the thicknesses of different retinal layers of RP eyes, and its association with aqueous flare, which is used for measuring the intensity of intraocular inflammation. A total of 125 eyes of 64 patients with RP and 13 normal eyes were studied. The thicknesses of total neural retina,nerve fiber layer(NFL),ganglion cell layer(GCL),inner plexiform layer(IPL),inner nuclear layer(INL),outer layers and foveal thickness were measured in the optical coherence tomographic images. Aqueous flare was measured with a laser flare-cell meter. The associations between those parameters, visual acuity and visual field were determined in RP eyes using multivariate analysis. The results of this study showed the significant thickening of NFL, GCL and INL, the significant thinning of outer layers and the association of them with increased aqueous flare, whereas NFL and INL thickening associated with outer retinal thinning. These results can suggest the involvement of intraocular inflammation in the pathogenesis of inner retinal thickening as a secondary change following outer retinal degeneration. PMID:27653207

  12. Differential pattern of RP1 mutations in retinitis pigmentosa

    PubMed Central

    Zhang, Xin; Chen, Li Jia; Law, Jonathan P.; Lai, Timothy Y.Y.; Chiang, Sylvia W.Y.; Tam, Pancy O.S.; Chu, Kwan Yi; Wang, Ningli; Zhang, Mingzhi

    2010-01-01

    Purpose Retinitis pigmentosa 1 (RP1) is a major gene responsible for both autosomal dominant and autosomal recessive retinitis pigmentosa (RP). We have previously identified three disease-causing mutations out of 174 RP patients. In this study, we investigated a new cohort of Chinese RP patients to further evaluate the contribution of RP1 mutations to cause RP. Methods A group of 55 nonsyndromic RP patients, the majority of them isolated cases or without information on family history, were screened for mutations in the entire coding sequences of RP1, using direct DNA sequencing. All detected variants were genotyped in 190 controls, while the three putative mutations were additionally genotyped in 362 controls subjects. Web-based programs, including PolyPhen, Sorting Intolerant from Tolerant (SIFT), Prediction of Pathological Mutations (PMUT), Single Amino Acid Polymorphism Disease-Association Predictor (SAP), ScanProsite, and ClustalW2, were used to predict the potential functional and structural impacts of the missense variants on RP1. Results A total of 14 sequence changes were identified. Among them, five were novel and found only in the RP patients. Two missense variants (p.K1370E and p.R1652L), which are conserved in primates, were predicted to have functional and structural impacts on the RP1 protein. The other three variants (c.787+34T>C, p.I408L and p.L2015L) were considered benign. Conclusions If these two novel missense variants are in fact pathogenic, then RP1 mutations account for approximately 2.18% (5/229) of RP cases in our Chinese cohort; this is similar to other ethnic groups. However, a relatively higher frequency of missense mutations found in the Chinese patients may suggest an ethnic diversity in the RP1 mutation patterns. PMID:20664799

  13. Sildenafil alters retinal function in mouse carriers of retinitis pigmentosa.

    PubMed

    Nivison-Smith, Lisa; Zhu, Yuan; Whatham, Andrew; Bui, Bang V; Fletcher, Erica L; Acosta, Monica L; Kalloniatis, Michael

    2014-11-01

    Sildenafil, the active ingredient in Viagra, has been reported to cause transient visual disturbance from inhibition of phosphodiesterase 6 (PDE6), a key enzyme in the visual phototransduction pathway. This study investigated the effects of sildenafil on the rd1(+/-) mouse, a model for carriers of Retinitis Pigmentosa which exhibit normal vision but may have a lower threshold for cellular stress caused by sildenafil due to a heterozygous mutation in PDE6. Sildenafil caused a dose-dependent decrease in electroretinogram (ERG) responses of normal mice which mostly recovered two days post administration. In contrast, rd1(+/-) mice exhibited a significantly reduced photoreceptor and a supernormal bipolar cell response to sildenafil within 1 h of treatment. Carrier mice retinae took two weeks to return to baseline levels suggesting sildenafil has direct effects on both the inner and outer retina and these effects differ significantly between normal and carrier mice. Anatomically, an increase in expression of the early apoptotic marker, cytochrome C in rd1(+/-) mice indicated that the effects of sildenafil on visual function may lead to degeneration. The results of this study are significant considering approximately 1 in 50 people are likely to be carriers of recessive traits leading to retinal degeneration. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Gene Therapy in Patient-specific Stem Cell Lines and a Preclinical Model of Retinitis Pigmentosa With Membrane Frizzled-related Protein Defects

    PubMed Central

    Li, Yao; Wu, Wen-Hsuan; Hsu, Chun-Wei; Nguyen, Huy V; Tsai, Yi-Ting; Chan, Lawrence; Nagasaki, Takayuki; Maumenee, Irene H; Yannuzzi, Lawrence A; Hoang, Quan V; Hua, Haiqing; Egli, Dieter; Tsang, Stephen H

    2014-01-01

    Defects in Membrane Frizzled-related Protein (MFRP) cause autosomal recessive retinitis pigmentosa (RP). MFRP codes for a retinal pigment epithelium (RPE)-specific membrane receptor of unknown function. In patient-specific induced pluripotent stem (iPS)-derived RPE cells, precise levels of MFRP, and its dicistronic partner CTRP5, are critical to the regulation of actin organization. Overexpression of CTRP5 in naïve human RPE cells phenocopied behavior of MFRP-deficient patient RPE (iPS-RPE) cells. AAV8 (Y733F) vector expressing human MFRP rescued the actin disorganization phenotype and restored apical microvilli in patient-specific iPS-RPE cell lines. As a result, AAV-treated MFRP mutant iPS-RPE recovered pigmentation and transepithelial resistance. The efficacy of AAV-mediated gene therapy was also evaluated in Mfrprd6/Mfrprd6 mice—an established preclinical model of RP—and long-term improvement in visual function was observed in AAV-Mfrp-treated mice. This report is the first to indicate the successful use of human iPS-RPE cells as a recipient for gene therapy. The observed favorable response to gene therapy in both patient-specific cell lines, and the Mfrprd6/Mfrprd6 preclinical model suggests that this form of degeneration caused by MFRP mutations is a potential target for interventional trials. PMID:24895994

  15. Gene therapy in patient-specific stem cell lines and a preclinical model of retinitis pigmentosa with membrane frizzled-related protein defects.

    PubMed

    Li, Yao; Wu, Wen-Hsuan; Hsu, Chun-Wei; Nguyen, Huy V; Tsai, Yi-Ting; Chan, Lawrence; Nagasaki, Takayuki; Maumenee, Irene H; Yannuzzi, Lawrence A; Hoang, Quan V; Hua, Haiqing; Egli, Dieter; Tsang, Stephen H

    2014-09-01

    Defects in Membrane Frizzled-related Protein (MFRP) cause autosomal recessive retinitis pigmentosa (RP). MFRP codes for a retinal pigment epithelium (RPE)-specific membrane receptor of unknown function. In patient-specific induced pluripotent stem (iPS)-derived RPE cells, precise levels of MFRP, and its dicistronic partner CTRP5, are critical to the regulation of actin organization. Overexpression of CTRP5 in naïve human RPE cells phenocopied behavior of MFRP-deficient patient RPE (iPS-RPE) cells. AAV8 (Y733F) vector expressing human MFRP rescued the actin disorganization phenotype and restored apical microvilli in patient-specific iPS-RPE cell lines. As a result, AAV-treated MFRP mutant iPS-RPE recovered pigmentation and transepithelial resistance. The efficacy of AAV-mediated gene therapy was also evaluated in Mfrp(rd6)/Mfrp(rd6) mice--an established preclinical model of RP--and long-term improvement in visual function was observed in AAV-Mfrp-treated mice. This report is the first to indicate the successful use of human iPS-RPE cells as a recipient for gene therapy. The observed favorable response to gene therapy in both patient-specific cell lines, and the Mfrp(rd6)/Mfrp(rd6) preclinical model suggests that this form of degeneration caused by MFRP mutations is a potential target for interventional trials.

  16. Diagnostic Challenges in Retinitis Pigmentosa: Genotypic Multiplicity and Phenotypic Variability

    PubMed Central

    Chang, Susie; Vaccarella, Leah; Olatunji, Sunday; Cebulla, Colleen; Christoforidis, John

    2011-01-01

    Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders. Diagnosis can be challenging as more than 40 genes are known to cause non-syndromic RP and phenotypic expression can differ significantly resulting in variations in disease severity, age of onset, rate of progression, and clinical findings. We describe the clinical manifestations of RP, the more commonly known causative gene mutations, and the genotypic-phenotypic correlation of RP. PMID:22131872

  17. Targeting the Proteostasis Network in Rhodopsin Retinitis Pigmentosa.

    PubMed

    Parfitt, David A; Cheetham, Michael E

    2016-01-01

    Mutations in rhodopsin are one of the most common causes of retinitis pigmentosa (RP). Misfolding of rhodopsin can result in disruptions in cellular protein homeostasis, or proteostasis. There is currently no available treatment for RP. In this review, we discuss the different approaches currently being investigated for treatment of rhodopsin RP, focusing on the potential of manipulation of the proteostasis network as a therapeutic approach to combat retinal degeneration.

  18. Successful Vocational Rehabilitation of Clients with Retinitis Pigmentosa.

    ERIC Educational Resources Information Center

    Taheri-Araghi, M.; Hendren, G.

    1994-01-01

    Statistical analysis of 10 personal (client) variables and four program variables related to 76 people who became blind from retinitis pigmentosa revealed that 6 variables predicted clients' rehabilitation outcomes: age, gender, race, work status, amount of case-service money spent on the client's behalf, and number of changes in career objectives…

  19. Workplace-Based Management of Retinitis Pigmentosa: A Case Report.

    ERIC Educational Resources Information Center

    Herse, Peter; Yapp, Michael

    1999-01-01

    Discusses the workplace-based accommodations that allowed a 45-year-old Southeast Asian woman with a moderate hearing deficit, who was diagnosed with retinitis pigmentosa, to continue to perform her duties as a checkout operator. Emphasizes the importance of conducting workplace evaluations before providers offer advice on vocational matters. (CR)

  20. Successful Vocational Rehabilitation of Clients with Retinitis Pigmentosa.

    ERIC Educational Resources Information Center

    Taheri-Araghi, M.; Hendren, G.

    1994-01-01

    Statistical analysis of 10 personal (client) variables and four program variables related to 76 people who became blind from retinitis pigmentosa revealed that 6 variables predicted clients' rehabilitation outcomes: age, gender, race, work status, amount of case-service money spent on the client's behalf, and number of changes in career objectives…

  1. Workplace-Based Management of Retinitis Pigmentosa: A Case Report.

    ERIC Educational Resources Information Center

    Herse, Peter; Yapp, Michael

    1999-01-01

    Discusses the workplace-based accommodations that allowed a 45-year-old Southeast Asian woman with a moderate hearing deficit, who was diagnosed with retinitis pigmentosa, to continue to perform her duties as a checkout operator. Emphasizes the importance of conducting workplace evaluations before providers offer advice on vocational matters. (CR)

  2. X-linked dominant retinitis pigmentosa in an American family

    SciTech Connect

    McGuire, R.E.; Daiger, S.P.; Blanton, S.H.

    1994-09-01

    Retinitis pigmentosa is a genetically heterogeneous disease with autosomal dominant (adRP), autosomal recessive and X-linked forms. At least 3 forms of X-linked retinitis pigmentosa have been reported: RP2 which maps to Xp11.4-p 11.23, RP3 which maps to Xp21.1 and RP6, which maps to Xp21.3-p21.1. The X-linked forms of retinitis pigmentosa are generally considered to be recessive as female carriers are not affected or are much less affected than males. Here we report a five generation American family with X-linked retinitis pigmentosa in which both males and females are significantly affected. The disease locus in this family appears to be distinct from RP2 and RP3. The American family (UTAD054) presents with early-onset retinitis pigmentosa. The family appeared to fit an autosomal dominant pattern; however, linkage testing excluded all known adRP loci. Absence of male-to-male transmission in the pedigree suggested the possibility of X-linked dominant inheritance. Thus we tested six microsatellite markers that map to Xp (DXS987, DXS989, DXS993, DXS999, DXS1003 and DXS1110). Of these, DXS989 showed tight linkage with one allele (199) showing a 100% concordance with disease status. The odds favoring an X-linked dominant mode of inheritance in this family, versus autosomal dominant, are 10{sup 5}:1. In addition, recombinations for DXS999, and dXS1110, the two markers flanking DXS989, were observed in affected individuals. These data map the disease locus in this family to a 9 mb region on the X chromosome between Xp22.11 and Xp21.41. In addition, the recombinant individuals exclude close linkage to RP2 and RP3. The observance of high penetrance in females indicates that this family has X-linked dominant retinitis pigmentosa. We suggest that this mode of inheritance should be considered in other families with dominant retinitis pigmentosa but an absence of male-to-male transmission.

  3. Early structural anomalies observed by high-resolution imaging in two related cases of autosomal-dominant retinitis pigmentosa.

    PubMed

    Park, Sung Pyo; Lee, Winston; Bae, Eun Jin; Greenstein, Vivianne; Sin, Bum Ho; Chang, Stanley; Tsang, Stephen H

    2014-01-01

    The authors report the use of adaptive-optics scanning laser ophthalmoscopy (AO-SLO) to investigate RHO, D190N autosomal-dominant retinitis pigmentosa in two siblings (11 and 16 years old, respectively). Each patient exhibited distinct hyperautofluorescence patterns in which the outer borders corresponded to inner segment ellipsoid band disruption. Areas within the hyperautofluorescence patterns exhibited normal photoreceptor outer segments and retinal pigment epithelium. However, AO-SLO imaging revealed noticeable spacing irregularities in the cone mosaic. AO-SLO allows researchers to characterize retinal structural abnormalities with precision so that early structural changes in retinitis pigmentosa can be identified and reconciled with genetic findings.

  4. Early Structural Anomalies Observed by High-Resolution Imaging in Two Related Cases of Autosomal-Dominant Retinitis Pigmentosa

    PubMed Central

    Park, Sung Pyo; Lee, Winston; Bae, Eun Jin; Greenstein, Vivianne; Sin, Bum Ho; Chang, Stanley; Tsang, Stephen H.

    2015-01-01

    The authors report the use of adaptive-optics scanning laser ophthalmoscopy (AO-SLO) to investigate RHO, D190N autosomal-dominant retinitis pigmentosa in two siblings (11 and 16 years old, respectively). Each patient exhibited distinct hyperautofluorescence patterns in which the outer borders corresponded to inner segment ellipsoid band disruption. Areas within the hyperautofluorescence patterns exhibited normal photoreceptor outer segments and retinal pigment epithelium. However, AO-SLO imaging revealed noticeable spacing irregularities in the cone mosaic. AO-SLO allows researchers to characterize retinal structural abnormalities with precision so that early structural changes in retinitis pigmentosa can be identified and reconciled with genetic findings. PMID:25215869

  5. Unravelling the genetic basis of simplex Retinitis Pigmentosa cases

    PubMed Central

    Bravo-Gil, Nereida; González-del Pozo, María; Martín-Sánchez, Marta; Méndez-Vidal, Cristina; Rodríguez-de la Rúa, Enrique; Borrego, Salud; Antiñolo, Guillermo

    2017-01-01

    Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy (IRD) characterized ultimately by photoreceptors degeneration. Exhibiting great clinical and genetic heterogeneity, RP can be inherited as an autosomal dominant (ad), autosomal recessive (ar) and X-linked (xl) disorder. Although the relative prevalence of each form varies somewhat between populations, a major proportion (41% in Spain) of patients represent simplex cases (sRP) in which the mode of inheritance is unknown. Molecular genetic diagnostic is crucial, but also challenging, for sRP patients because any of the 81 RP genes identified to date may be causative. Herein, we report the use of a customized targeted gene panel consisting of 68 IRD genes for the molecular characterization of 106 sRP cases. The diagnostic rate was 62.26% (66 of 106) with a proportion of clinical refinements of 30.3%, demonstrating the high efficiency of this genomic approach even for clinically ambiguous cases. The high number of patients diagnosed here has allowed us to study in detail the genetic basis of the sRP. The solved sRP cohort is composed of 62.1% of arRP cases, 24.2% of adRP and 13.6% of xlRP, which implies consequences for counselling of patients and families. PMID:28157192

  6. Unravelling the genetic basis of simplex Retinitis Pigmentosa cases.

    PubMed

    Bravo-Gil, Nereida; González-Del Pozo, María; Martín-Sánchez, Marta; Méndez-Vidal, Cristina; Rodríguez-de la Rúa, Enrique; Borrego, Salud; Antiñolo, Guillermo

    2017-02-03

    Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy (IRD) characterized ultimately by photoreceptors degeneration. Exhibiting great clinical and genetic heterogeneity, RP can be inherited as an autosomal dominant (ad), autosomal recessive (ar) and X-linked (xl) disorder. Although the relative prevalence of each form varies somewhat between populations, a major proportion (41% in Spain) of patients represent simplex cases (sRP) in which the mode of inheritance is unknown. Molecular genetic diagnostic is crucial, but also challenging, for sRP patients because any of the 81 RP genes identified to date may be causative. Herein, we report the use of a customized targeted gene panel consisting of 68 IRD genes for the molecular characterization of 106 sRP cases. The diagnostic rate was 62.26% (66 of 106) with a proportion of clinical refinements of 30.3%, demonstrating the high efficiency of this genomic approach even for clinically ambiguous cases. The high number of patients diagnosed here has allowed us to study in detail the genetic basis of the sRP. The solved sRP cohort is composed of 62.1% of arRP cases, 24.2% of adRP and 13.6% of xlRP, which implies consequences for counselling of patients and families.

  7. Pre-mRNA splicing and retinitis pigmentosa

    PubMed Central

    Mordes, Daniel; Luo, Xiaoyan; Kar, Amar; Kuo, David; Xu, Lili; Fushimi, Kazuo; Yu, Guowu; Sternberg, Paul; Wu, Jane Y.

    2009-01-01

    Retinitis pigmentosa (RP) is a group of genetically and clinically heterogeneous retinal diseases and a common cause of blindness. Among the 12 autosomal dominant RP (adRP) genes identified, four encode ubiquitously expressed proteins involved in pre-mRNA splicing, demonstrating the important role that pre-mRNA splicing plays in the pathogenesis of retinal degeneration. This review focuses on recent progress in identifying adRP mutations in genes encoding pre-mRNA splicing factors and the potential underlying molecular mechanisms. PMID:17110909

  8. Genetic heterogeneity and consanguinity lead to a “double hit”: Homozygous mutations of MYO7A and PDE6B in a patient with retinitis pigmentosa

    PubMed Central

    Goldenberg-Cohen, Nitza; Banin, Eyal; Zalzstein, Yael; Cohen, Ben; Rotenstreich, Ygal; Rizel, Leah; Basel-Vanagaite, Lina

    2013-01-01

    Purpose Retinitis pigmentosa (RP), the most genetically heterogeneous disorder in humans, actually represents a group of pigmentary retinopathies characterized by night blindness followed by visual-field loss. RP can appear as either syndromic or nonsyndromic. One of the most common forms of syndromic RP is Usher syndrome, characterized by the combination of RP, hearing loss, and vestibular dysfunction. Methods The underlying cause of the appearance of syndromic and nonsyndromic RP in three siblings from a consanguineous Israeli Muslim Arab family was studied with whole-genome homozygosity mapping followed by whole exome sequencing. Results The family was found to segregate novel mutations of two different genes: myosin VIIA (MYO7A), which causes type 1 Usher syndrome, and phosphodiesterase 6B, cyclic guanosine monophosphate-specific, rod, beta (PDE6B), which causes nonsyndromic RP. One affected child was homozygous for both mutations. Since the retinal phenotype seen in this patient results from overlapping pathologies, one might expect to find severe retinal degeneration. Indeed, he was diagnosed with RP based on an abnormal electroretinogram (ERG) at a young age (9 months). However, this early diagnosis may be biased, as two of his older siblings had already been diagnosed, leading to increased awareness. At the age of 32 months, he had relatively good vision with normal visual fields. Further testing of visual function and structure at different ages in the three siblings is needed to determine whether the two RP-causing genes mutated in this youngest sibling confer increased disease severity. Conclusions This report further supports the genetic heterogeneity of RP, and demonstrates how consanguinity could increase intrafamilial clustering of multiple hereditary diseases. Moreover, this report provides a unique opportunity to study the clinical implications of the coexistence of pathogenic mutations in two RP-causative genes in a human patient. PMID:23882135

  9. Multiprotein Complexes of Retinitis Pigmentosa GTPase Regulator (RPGR), a Ciliary Protein Mutated in X-Linked Retinitis Pigmentosa (XLRP)

    PubMed Central

    Murga-Zamalloa, Carlos; Swaroop, Anand

    2012-01-01

    Mutations in Retinitis Pigmentosa GTPase Regulator (RPGR) are a frequent cause of X-linked Retinitis Pigmentosa (XLRP). The RPGR gene undergoes extensive alternative splicing and encodes for distinct protein isoforms in the retina. Extensive studies using isoform-specific antibodies and mouse mutants have revealed that RPGR predominantly localizes to the transition zone to primary cilia and associates with selected ciliary and microtubule-associated assemblies in photoreceptors. In this chapter, we have summarized recent advances on understanding the role of RPGR in photoreceptor protein trafficking. We also provide new evidence that suggests the existence of discrete RPGR multiprotein complexes in photoreceptors. Piecing together the RPGR-interactome in different subcellular compartments should provide critical insights into the role of alternative RPGR isoforms in associated orphan and syndromic retinal degenerative diseases. PMID:20238008

  10. Pharmacological approaches to retinitis pigmentosa: A laboratory perspective.

    PubMed

    Guadagni, Viviana; Novelli, Elena; Piano, Ilaria; Gargini, Claudia; Strettoi, Enrica

    2015-09-01

    Retinal photoreceptors are highly specialized and performing neurons. Their cellular architecture is exquisitely designed to host a high concentration of molecules involved in light capture, phototransduction, electric and chemical signaling, membrane and molecular turnover, light and dark adaption, network activities etc. Such high efficiency and molecular complexity require a great metabolic demand, altogether conferring to photoreceptors particular susceptibility to external and internal insults, whose occurrence usually precipitate into degeneration of these cells and blindness. In Retinitis Pigmentosa, an impressive number of mutations in genes expressed in the retina and coding for a large varieties of proteins leads to the progressive death of photoreceptors and blindness. Recent advances in molecular tools have greatly facilitated the identification of the underlying genetics and molecular bases of RP leading to the successful implementation of gene therapy for some types of mutations, with visual restoration in human patients. Yet, genetic heterogeneity of RP makes mutation-independent approaches highly desirable, although many obstacles pave the way to general strategies for treating this complex disease, which remains orphan. The review will focus on treatments for RP based on pharmacological tools, choosing, among the many ongoing studies, approaches which rely on strong experimental evidence or rationale. For perspective treatments, new concepts are foreseen to emerge from basic studies elucidating the pathways connecting the primary mutations to photoreceptor death, possibly revealing common molecular targets for drug intervention.

  11. Early-Onset X-Linked Retinitis Pigmentosa in a Heterozygous Female Harboring an Intronic Donor Splice Site Mutation in the Retinitis Pigmentosa GTPase Regulator Gene.

    PubMed

    Shifera, Amde Selassie; Kay, Christine Nichols

    2015-01-01

    To report a heterozygous female presenting with an early-onset and severe form of X-linked retinitis pigmentosa (XLRP). This is a case series presenting the clinical findings in a heterozygous female with XLRP and two of her family members. Fundus photography, fundus autofluorescence, ocular coherence tomography, and visual perimetry are presented. The proband reported here is a heterozygous female who presented at the age of 8 years with an early onset and aggressive form of XLRP. The patient belongs to a four-generation family with a total of three affected females and four affected males. The patient was initially diagnosed with retinitis pigmentosa (RP) at the age of 4 years. Genetic testing identified a heterozygous donor splice site mutation in intron 1 (IVS1 + 1G > A) of the retinitis pigmentosa GTPase regulator gene. The father of the proband was diagnosed with RP when he was a young child. The sister of the proband, evaluated at the age of 6 years, showed macular pigmentary changes. Although carriers of XLRP are usually asymptomatic or have a mild disease of late onset, the proband presented here exhibited an early-onset, aggressive form of the disease. It is not clear why some carrier females manifest a severe phenotype. A better understanding of the genetic processes involved in the penetrance and expressivity of XLRP in heterozygous females could assist in providing the appropriate counseling to affected families.

  12. Activation of Bax in three models of retinitis pigmentosa.

    PubMed

    Comitato, Antonella; Sanges, Daniela; Rossi, Alessandra; Humphries, Marian M; Marigo, Valeria

    2014-05-13

    The process of photoreceptor cell death in retinitis pigmentosa is still not well characterized, and identification of common mechanisms will be instrumental for development of therapeutic strategies. Here we investigated activation of Bax in rd1, P23H transgenic, and Rho knockout retinas. Bax activation was evaluated by immunofluorescence using anti-activated Bax-specific antibodies and by Western blotting on mitochondrial protein extracts. Knockdown of cathepsin D, calpain 1, and calpain 2 was achieved by short hairpin RNA (shRNA) delivery in rd1 mutant photoreceptors cells differentiated from retinal neurospheres. The mechanism of Bax activation through calpains was evaluated in vivo by intravitreal injection of calpastatin. We defined activation and mitochondrial localization of Bax as well as activation of calpains and cathepsin D in the three models of retinitis pigmentosa. Taking advantage of an in vitro culture system for rd1 mutant photoreceptors, we unraveled the mechanism of Bax activation. We demonstrated that calpain 1 and cathepsin D contributed to activation of Bax and to apoptosis-inducing factor (Aif) nuclear translocation. In vivo interference with calpain activity blocks Bax activation in the rd1 and Rho knockout retinas and reduces activation in the P23H transgenic retina. Activation of Bax was observed in all three models of retinitis pigmentosa and leads to neurodamage by localization at the mitochondrion. Our data suggest that Bax can be envisaged as one of the promising target molecules for restraining photoreceptor degeneration. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  13. The bacterial toxin CNF1 as a tool to induce retinal degeneration reminiscent of retinitis pigmentosa

    PubMed Central

    Guadagni, Viviana; Cerri, Chiara; Piano, Ilaria; Novelli, Elena; Gargini, Claudia; Fiorentini, Carla; Caleo, Matteo; Strettoi, Enrica

    2016-01-01

    Retinitis pigmentosa (RP) comprises a group of inherited pathologies characterized by progressive photoreceptor degeneration. In rodent models of RP, expression of defective genes and retinal degeneration usually manifest during the first weeks of postnatal life, making it difficult to distinguish consequences of primary genetic defects from abnormalities in retinal development. Moreover, mouse eyes are small and not always adequate to test pharmacological and surgical treatments. An inducible paradigm of retinal degeneration potentially extensible to large animals is therefore desirable. Starting from the serendipitous observation that intraocular injections of a Rho GTPase activator, the bacterial toxin Cytotoxic Necrotizing Factor 1 (CNF1), lead to retinal degeneration, we implemented an inducible model recapitulating most of the key features of Retinitis Pigmentosa. The model also unmasks an intrinsic vulnerability of photoreceptors to the mechanism of CNF1 action, indicating still unexplored molecular pathways potentially leading to the death of these cells in inherited forms of retinal degeneration. PMID:27775019

  14. Psychological and Educational Recommendations for Working with Young People with Retinitis Pigmentosa

    ERIC Educational Resources Information Center

    Chacón-López, Helena; López-Justicia, Maria D.; Vervloed, Mathijs P. J.

    2014-01-01

    This article reviews the consequences of Retinitis Pigmentosa, a retinal degenerative disease with progressive reduction of the visual field, visual acuity, contrast sensitivity, and night blindness. Retinitis Pigmentosa is addressed from both a psychological and an educational standpoint, focusing on the impact on learning, emotional well-being,…

  15. Psychological and Educational Recommendations for Working with Young People with Retinitis Pigmentosa

    ERIC Educational Resources Information Center

    Chacón-López, Helena; López-Justicia, Maria D.; Vervloed, Mathijs P. J.

    2014-01-01

    This article reviews the consequences of Retinitis Pigmentosa, a retinal degenerative disease with progressive reduction of the visual field, visual acuity, contrast sensitivity, and night blindness. Retinitis Pigmentosa is addressed from both a psychological and an educational standpoint, focusing on the impact on learning, emotional well-being,…

  16. Health services utilization and cost of retinitis pigmentosa.

    PubMed

    Frick, Kevin D; Roebuck, M Christopher; Feldstein, Joshua I; McCarty, Catherine A; Grover, Lori L

    2012-05-01

    To estimate annual per-patient health services utilization and costs of retinitis pigmentosa (RP) in the United States. A retrospective claims analysis of patients with RP (N = 2990) and a 1:1 exactly matched cohort of non-RP patients was conducted using the MarketScan Commercial and Medicare Supplemental Databases. Individuals were continuously enrolled in a commercial health plan or employer-sponsored health insurance for at least 1 year. The following annual outcomes were analyzed using nonlinear multivariate models: inpatient hospital admissions, inpatient hospital days, emergency department visits, outpatient physician visits, and prescription drug refills and inpatient and outpatient medical, pharmacy, and total health care costs. Patients with RP had 0.04 more hospital admissions (P < .001), 0.19 more inpatient hospital days (P < .02), 0.05 more emergency department visits (P < .01), 2.74 more outpatient visits (P < .001), and 2.18 additional prescription drug fills (P < .001) annually compared with their non-RP counterparts. Health care expenditures were significantly higher for patients with RP, who cost $894, $4855, and $452 more for inpatient, outpatient, and pharmacy services, respectively (P < .001). Overall health care costs were $7317 more per patient per year in the RP cohort, with expenditures varying considerably by age. Patients with RP consume substantially greater amounts of health services with significantly higher health care costs. Treatments that slow, halt, or possibly restore RP-related vision loss may prove cost-effective for payers and society.

  17. Whole-exome sequencing identifies a novel homozygous frameshift mutation in the PROM1 gene as a causative mutation in two patients with sporadic retinitis pigmentosa

    PubMed Central

    LIU, SANMEI; XIE, LAN; YUE, JUN; MA, TAO; PENG, CHUNYAN; QIU, BIYUAN; YANG, ZHENGLIN; YANG, JIYUN

    2016-01-01

    Retinitis pigmentosa (RP) refers to a heterogeneous group of inherited retinal diseases caused by the loss of photoreceptors. The present study aimed to identify the gene mutations responsible for RP in two patients diagnosed with sporadic RP using next-generation sequencing technology. For this purpose, two patients with sporadic RP and family members (namely parents and siblings) were recruited into this study and underwent a complete ophthalmological assessment. Whole-exome sequencing (WES) was performed on genomic DNA samples isolated from peripheral leukocytes which had been obtained from the two patients diagnosed with sporadic RP. WES data were annotated and filtered against four public databases and one in-house database. Subsequently, Sanger sequencing was performed in order to determine whether any of the candidate variants co-segregated with the disease phenotype in the families. A homozygous frameshift mutation, c.1445dupT (p.F482fs) in exon 12 of the PROM1 gene (MIM: 604365), satisfied a recessive inheritance model and showed complete co-segregation of the mutation with the disease phenotype in the families. The same mutation was not detected in the 200 ethnically-matched control samples by Sanger sequencing. The novel homozygous mutation c.1445dupT (p.F482fs) in the PROM1 gene was identified as a causative mutation for RP. Thus, the identification of this mutation has further expanded the existing spectrum of PROM1 mutations in patients with RP, thereby assisting in the molecular diagnosis of RP and enhancing our understanding of genotype-phenotype correlations in order to provide effective genetic counseling. PMID:27082927

  18. Identification of a 2 Mb Human Ortholog of Drosophila eyes shut/spacemaker that Is Mutated in Patients with Retinitis Pigmentosa

    PubMed Central

    Collin, Rob W.J.; Littink, Karin W.; Klevering, B. Jeroen; van den Born, L. Ingeborgh; Koenekoop, Robert K.; Zonneveld, Marijke N.; Blokland, Ellen A.W.; Strom, Tim M.; Hoyng, Carel B.; den Hollander, Anneke I.; Cremers, Frans P.M.

    2008-01-01

    In patients with autosomal-recessive retinitis pigmentosa (arRP), homozygosity mapping was performed for detection of regions harboring genes that might be causative for RP. In one affected sib pair, a shared homozygous region of 5.0 Mb was identified on chromosome 6, within the RP25 locus. One of the genes residing in this interval was the retina-expressed gene EGFL11. Several genes resembling EGFL11 were predicted just centromeric of EGFL11. Extensive long-range RT-PCR, combined with 5′- and 3′- RACE analysis, resulted in the identification of a 10-kb transcript, starting with the annotated exons of EGFL11 and spanning 44 exons and 2 Mb of genomic DNA. The transcript is predicted to encode a 3165-aa extracellular protein containing 28 EGF-like and five laminin A G-like domains. Interestingly, the second part of the protein was found to be the human ortholog of Drosophila eyes shut (eys), also known as spacemaker, a protein essential for photoreceptor morphology. Mutation analysis in the sib pair homozygous at RP25 revealed a nonsense mutation (p.Tyr3156X) segregating with RP. The same mutation was identified homozygously in three arRP siblings of an unrelated family. A frame-shift mutation (pPro2238ProfsX16) was found in an isolated RP patient. In conclusion, we identified a gene, coined eyes shut homolog (EYS), consisting of EGFL11 and the human ortholog of Drosophila eys, which is mutated in patients with arRP. With a size of 2 Mb, it is one of the largest human genes, and it is by far the largest retinal dystrophy gene. The discovery of EYS might shed light on a critical component of photoreceptor morphogenesis. PMID:18976725

  19. Identification of a 2 Mb human ortholog of Drosophila eyes shut/spacemaker that is mutated in patients with retinitis pigmentosa.

    PubMed

    Collin, Rob W J; Littink, Karin W; Klevering, B Jeroen; van den Born, L Ingeborgh; Koenekoop, Robert K; Zonneveld, Marijke N; Blokland, Ellen A W; Strom, Tim M; Hoyng, Carel B; den Hollander, Anneke I; Cremers, Frans P M

    2008-11-01

    In patients with autosomal-recessive retinitis pigmentosa (arRP), homozygosity mapping was performed for detection of regions harboring genes that might be causative for RP. In one affected sib pair, a shared homozygous region of 5.0 Mb was identified on chromosome 6, within the RP25 locus. One of the genes residing in this interval was the retina-expressed gene EGFL11. Several genes resembling EGFL11 were predicted just centromeric of EGFL11. Extensive long-range RT-PCR, combined with 5'- and 3'- RACE analysis, resulted in the identification of a 10-kb transcript, starting with the annotated exons of EGFL11 and spanning 44 exons and 2 Mb of genomic DNA. The transcript is predicted to encode a 3165-aa extracellular protein containing 28 EGF-like and five laminin A G-like domains. Interestingly, the second part of the protein was found to be the human ortholog of Drosophila eyes shut (eys), also known as spacemaker, a protein essential for photoreceptor morphology. Mutation analysis in the sib pair homozygous at RP25 revealed a nonsense mutation (p.Tyr3156X) segregating with RP. The same mutation was identified homozygously in three arRP siblings of an unrelated family. A frame-shift mutation (pPro2238ProfsX16) was found in an isolated RP patient. In conclusion, we identified a gene, coined eyes shut homolog (EYS), consisting of EGFL11 and the human ortholog of Drosophila eys, which is mutated in patients with arRP. With a size of 2 Mb, it is one of the largest human genes, and it is by far the largest retinal dystrophy gene. The discovery of EYS might shed light on a critical component of photoreceptor morphogenesis.

  20. Thermal Stability of Rhodopsin and Progression of Retinitis Pigmentosa

    PubMed Central

    Liu, Monica Yun; Liu, Jian; Mehrotra, Devi; Liu, Yuting; Guo, Ying; Baldera-Aguayo, Pedro A.; Mooney, Victoria L.; Nour, Adel M.; Yan, Elsa C. Y.

    2013-01-01

    Over 100 point mutations in the rhodopsin gene have been associated with retinitis pigmentosa (RP), a family of inherited visual disorders. Among these, we focused on characterizing the S186W mutation. We compared the thermal properties of the S186W mutant with another RP-causing mutant, D190N, and with WT rhodopsin. To assess thermal stability, we measured the rate of two thermal reactions contributing to the thermal decay of rhodopsin as follows: thermal isomerization of 11-cis-retinal and hydrolysis of the protonated Schiff base linkage between the 11-cis-retinal chromophore and opsin protein. We used UV-visible spectroscopy and HPLC to examine the kinetics of these reactions at 37 and 55 °C for WT and mutant rhodopsin purified from HEK293 cells. Compared with WT rhodopsin and the D190N mutant, the S186W mutation dramatically increases the rates of both thermal isomerization and dark state hydrolysis of the Schiff base by 1–2 orders of magnitude. The results suggest that the S186W mutant thermally destabilizes rhodopsin by disrupting a hydrogen bond network at the receptor's active site. The decrease in the thermal stability of dark state rhodopsin is likely to be associated with higher levels of dark noise that undermine the sensitivity of rhodopsin, potentially accounting for night blindness in the early stages of RP. Further studies of the thermal stability of additional pathogenic rhodopsin mutations in conjunction with clinical studies are expected to provide insight into the molecular mechanism of RP and test the correlation between rhodopsin's thermal stability and RP progression in patients. PMID:23625926

  1. Screen of the IMPDH1 gene among patients with dominant retinitis pigmentosa and clinical features associated with the most common mutation, Asp226Asn.

    PubMed

    Wada, Yuko; Sandberg, Michael A; McGee, Terri L; Stillberger, Melissa A; Berson, Eliot L; Dryja, Thaddeus P

    2005-05-01

    To determine the frequency of mutations in IMPDH1 among patients with autosomal dominant retinitis pigmentosa (RP), to characterize the clinical features of patients with the Asp226Asn mutation in this gene, and to compare these features with those found among patients with selected dominant mutations in other RP genes. The coding sequence and the adjacent flanking intron sequences of all 14 coding exons were sequenced in 183 unrelated patients with dominant RP. The clinical findings evaluated included visual acuity, refractive error, visual field area measured with the Goldmann perimeter, final dark-adaptation threshold, full-field electroretinogram (ERG) amplitudes, cataract, and funduscopic bone spicule pigmentation. The mutation Asp226Asn was identified in 6 of the 183 unrelated patients with RP. One patient carried the novel, possibly pathogenic, change Lys238Glu. There was approximately a 100-fold variation in ERG amplitudes among patients of similar age with the Asp226Asn mutation. Patients had similar reductions of rod-plus-cone 0.5-Hz ERG amplitude and cone 30-Hz ERG amplitude. For a given amount of remaining visual field, there was a larger ERG amplitude in IMPDH1-carrying patients (average 0.5-Hz ERG/visual field ratio = 9.5 nV/deg(2)) compared with groups of patients with the RP1 mutation Arg677End (2.8 nV/deg(2)), the rhodopsin (RHO) mutation Pro23His (5.1 nV/deg(2)), or the RHO mutation Pro347Leu (1.7 nV/deg(2)). IMPDH1 mutations account for approximately 2% of cases of dominant RP in North America. The most frequent mutation, Asp226Asn, appears to cause at least as much loss of rod function as cone function. Patients with this form of RP retain, on average, two to five times more ERG amplitude per unit of remaining visual area than patients with three other forms of dominant RP.

  2. Decreased retinal-choroidal blood flow in retinitis pigmentosa as measured by MRI.

    PubMed

    Zhang, Yi; Harrison, Joseph M; Nateras, Oscar San Emeterio; Chalfin, Steven; Duong, Timothy Q

    2013-06-01

    To evaluate retinal and choroidal blood flow (BF) using high-resolution magnetic resonance imaging (MRI) as well as visual function measured by the electroretinogram (ERG) in patients with retinitis pigmentosa (RP). MRI studies were performed in 6 RP patients (29-67 years) and 5 healthy volunteers (29-64 years) on a 3-Tesla scanner with a custom-made surface coil. Quantitative BF was measured using the pseudo-continuous arterial spin-labeling technique at 0.5 × 0.8 × 6.0 mm. Full-field ERGs of all patients were recorded. Amplitudes and implicit times of standard ERGs were analyzed. Basal BF in the posterior retinal-choroid was 142 ± 16 ml/100ml/min (or 1.14 ± 0.13 μl/mm(2)/min) in the control group and was 70 ±19 ml/100ml/min (or 0.56 ± 0.15 μl/mm(2)/min) in the RP group. Retinal-choroidal BF was significantly reduced by 52 ± 8 % in RP patients compared to controls (P<0.05). ERG a- and b-wave amplitudes of RP patients were reduced, and b-wave implicit times were delayed. There were statistically significant correlations between a-wave amplitude and BF value (r=0.9, P<0.05) but not between b-wave amplitude and BF value (r =0.7, P=0.2). This study demonstrates a novel non-invasive MRI approach to measure quantitative retinal and choroidal BF in RP patients. We found that retinal-choroidal BF was markedly reduced and significantly correlated with reduced amplitudes of the a-wave of the standard combined ERG.

  3. Frequency Domain Electroretinography in Retinitis Pigmentosa versus Normal Eyes.

    PubMed

    Hassan-Karimi, Homa; Jafarzadehpur, Ebrahim; Blouri, Bahram; Hashemi, Hassan; Sadeghi, Arash Zare; Mirzajani, Ali

    2012-01-01

    To compare electroretinogram (ERG) characteristics in patients with retinitis pigmentosa (RP) and normal subjects using frequency domain analysis. Five basic ERG recordings were performed in normal subjects and patients with a clinical diagnosis of RP according to the ISCEV (International Society of Clinical Electrophysiology of Vision) protocol. Frequency domain analysis was performed by MATLAB software. Different frequency domain parameters were compared between the study groups. Peak frequency (Fmod) of flicker and oscillatory responses in RP patients showed significant (P<0.0001) high pass response as compared to normal controls. Peak frequency (Fmod) of the other responses was not significantly different between the two groups. In addition to conventional ERG using time domain methods, frequency domain analysis may be useful for diagnosis of RP. Oscillatory and flicker responses may be analyzed in frequency domain. Fast Fourier transform may reveal two distinct high pass responses (shift to higher frequencies) in Fmod. Time and frequency domain analyses may be performed simultaneously with many modern ERG machines and may therefore be recommended in RP patients.

  4. Recent Advances of Stem Cell Therapy for Retinitis Pigmentosa

    PubMed Central

    He, Yuxi; Zhang, Yan; Liu, Xin; Ghazaryan, Emma; Li, Ying; Xie, Jianan; Su, Guanfang

    2014-01-01

    Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by progressive loss of photoreceptors and eventually leads to retina degeneration and atrophy. Until now, the exact pathogenesis and etiology of this disease has not been clear, and many approaches for RP therapies have been carried out in animals and in clinical trials. In recent years, stem cell transplantation-based attempts made some progress, especially the transplantation of bone marrow-derived mesenchymal stem cells (BMSCs). This review will provide an overview of stem cell-based treatment of RP and its main problems, to provide evidence for the safety and feasibility for further clinical treatment. PMID:25141102

  5. Novel variants of RPGR in X-linked retinitis pigmentosa families and genotype-phenotype correlation.

    PubMed

    Parmeggiani, Francesco; Barbaro, Vanessa; Migliorati, Angelo; Raffa, Paolo; Nespeca, Patrizia; De Nadai, Katia; Del Vecchio, Claudia; Palù, Giorgio; Parolin, Cristina; Di Iorio, Enzo

    2017-03-10

    To identify novel mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene and retinitis pigmentosa 2 (RP2) gene underlying X-linked retinitis pigmentosa (XLRP) and assess genotype-phenotype correlations. The patient cohort, consisting of 13 individuals from 3 unrelated XLRP families, underwent comprehensive ophthalmologic examination. The open reading frames of RPGR and RP2 were analyzed with Sanger sequencing in each patient. The identified genetic variants were defined as mutations or polymorphisms on the basis of their pathological effect. We found 3 genetic variants: a novel mutation c.1591G>T in exon 14 and a novel polymorphism c.1105C>T in exon 10, resulting in p.Glu531* and p.Arg369Cys of RPGR gene, respectively, and one already known mutation c.413A>G in exon 2, resulting in a p.Glu138Gly of RP2 gene. Considering our XLRP probands, RPGR-related phenotypic damages were similar and less severe than those of the patient with the RP2 mutation. On the other hand, the female carriers of XLRP variants showed different RPGR-related consequences, ranging from rods hypofunctionality in c.1591G>T nonsense heterozygosity to no retinal changes in c.1105C>T polymorphic heterozygosity. These findings broaden the spectrum of RPGR mutations and phenotypic variability of the disease, which will be useful for genetic consultation and diagnosis in the future.

  6. Progressive constriction of the hyperautofluorescent ring in retinitis pigmentosa.

    PubMed

    Lima, Luiz H; Burke, Tomas; Greenstein, Vivienne C; Chou, Chai Lin; Cella, Wener; Yannuzzi, Lawrence A; Tsang, Stephen H

    2012-04-01

    To evaluate the constriction of the hyperautofluorescent ring over time in patients with retinitis pigmentosa (RP). Prospective study. Fourteen eyes of 14 RP patients with a hyperautofluorescent ring were studied. Ring constriction was evaluated by measurements of its external and internal boundaries along the vertical and horizontal axes at baseline and at 12-, 24-, 36-, and 48-month follow-ups. Repeat fundus autofluorescence was obtained at 12, 24, 36, and 48 months in 13, 7, 5, and 1 eyes respectively. Spectral-domain optical coherence tomography (SD-OCT) images were obtained on 8 eyes and the horizontal extent of the inner segment/outer segment (IS/OS) junction was measured. SD-OCT was repeated at 12 and 24 months in 6 and 4 eyes respectively. The external boundaries of the ring were identified along the horizontal axis in 12 eyes and along the vertical axis in 13. Internal boundaries were identified in 7 eyes. Constriction was demonstrated in all patients except 1 who demonstrated minimal expansion of the internal boundary along the horizontal axis. SD-OCT measurements showed a decrease in the IS/OS junction length. Progressive constriction of the hyperautofluorescent ring and a concordant decrease in IS/OS junction length were observed over time. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Objective visual field determination in forensic ophthalmology with an optimized 4-channel multifocal VEP perimetry system: a case report of a patient with retinitis pigmentosa.

    PubMed

    Kaltwasser, C; Horn, F K; Kremers, J; Juenemann, A; Bergua, A

    2011-10-01

    We present the case of a 59-year-old male patient with progressive vision impairment and consecutive visual field narrowing ("tunnel view") for 7 years and a known retinitis pigmentosa for 5 years. The remaining Goldmann perimetric visual field at time reported was less than 5°. A request for blindness-related social benefits was rejected because an ophthalmologic expert assessment suggested malingering. This prompted us to assess an objective determination of the visual field using multifocal VEPs. Objective visual field recordings were performed with a four-channel multifocal VEP-perimeter using 58 stimulus fields (pattern reversal dartboard stimulus configuration). The correlated signal data were processed using an off-line method. At each field, the recording from the channel with the maximal signal-to-noise ratio (SNR) was retained, thus resulting in an SNR optimized virtual recording. Analysis of VEP signals was performed for each single field and concentric rings and compared to an average response measured in five healthy subjects. Substantial VEP responses could be identified in three fields within the innermost ring (eccentricity, 1.7°) for both eyes, although SNR was generally low. More eccentric stimuli did not elicit reliable VEP responses. The mfVEP recording was correlated with perimetric visual field data. The current SNR optimization by using the channel with the largest SNR provides a good method to extract useful data from recordings and may be appropriate for the use in forensic ophthalmology.

  8. Missense Mutations in a Retinal Pigment Epithelium Protein, Bestrophin-1, Cause Retinitis Pigmentosa

    PubMed Central

    Davidson, Alice E.; Millar, Ian D.; Urquhart, Jill E.; Burgess-Mullan, Rosemary; Shweikh, Yusrah; Parry, Neil; O'Sullivan, James; Maher, Geoffrey J.; McKibbin, Martin; Downes, Susan M.; Lotery, Andrew J.; Jacobson, Samuel G.; Brown, Peter D.; Black, Graeme C.M.; Manson, Forbes D.C.

    2009-01-01

    Bestrophin-1 is preferentially expressed at the basolateral membrane of the retinal pigmented epithelium (RPE) of the retina. Mutations in the BEST1 gene cause the retinal dystrophies vitelliform macular dystrophy, autosomal-dominant vitreochoroidopathy, and autosomal-recessive bestrophinopathy. Here, we describe four missense mutations in bestrophin-1, three that we believe are previously unreported, in patients diagnosed with autosomal-dominant and -recessive forms of retinitis pigmentosa (RP). The physiological function of bestrophin-1 remains poorly understood although its heterologous expression induces a Cl−-specific current. We tested the effect of RP-causing variants on Cl− channel activity and cellular localization of bestrophin-1. Two (p.L140V and p.I205T) produced significantly decreased chloride-selective whole-cell currents in comparison to those of wild-type protein. In a model system of a polarized epithelium, two of three mutations (p.L140V and p.D228N) caused mislocalization of bestrophin-1 from the basolateral membrane to the cytoplasm. Mutations in bestrophin-1 are increasingly recognized as an important cause of inherited retinal dystrophy. PMID:19853238

  9. EYS Mutations Causing Autosomal Recessive Retinitis Pigmentosa: Changes of Retinal Structure and Function with Disease Progression

    PubMed Central

    McGuigan, David B.; Heon, Elise; Cideciyan, Artur V.; Ratnapriya, Rinki; Lu, Monica; Sumaroka, Alexander; Roman, Alejandro J.; Batmanabane, Vaishnavi; Garafalo, Alexandra V.; Stone, Edwin M.; Jacobson, Samuel G.

    2017-01-01

    Mutations in the EYS (eyes shut homolog) gene are a common cause of autosomal recessive (ar) retinitis pigmentosa (RP). Without a mammalian model of human EYS disease, there is limited understanding of details of disease expression and rates of progression of the retinal degeneration. We studied clinically and with chromatic static perimetry, spectral-domain optical coherence tomography (OCT), and en face autofluoresence imaging, a cohort of 15 patients (ages 12–51 at first visit), some of whom had longitudinal data of function and structure. Rod sensitivity was able to be measured by chromatic perimetry in most patients at their earliest visits and some patients retained patchy rod function into the fifth decade of life. As expected from RP, cone sensitivity persisted after rod function was no longer measurable. The photoreceptor nuclear layer of the central retina was abnormal except at the fovea in most patients at first visit. Perifoveal disease measured over a period of years indicated that photoreceptor structural loss was followed by dysmorphology of the inner retina and loss of retinal pigment epithelial integrity. Although there could be variability in severity, preliminary analyses of the rates of vision loss suggested that EYS is a more rapidly progressive disease than other ciliopathies causing arRP, such as USH2A and MAK. PMID:28704921

  10. Screening of a large cohort of Leber congenital amaurosis and retinitis pigmentosa patients identifies novel LCA5 mutations and new genotype-phenotype correlations

    PubMed Central

    Sui, Ruifang; van den Born, L. Ingeborgh; Berson, Eliot L.; Ocaka, Louise A.; Davidson, Alice E.; Heckenlively, John R.; Branham, Kari; Ren, Huanan; Lopez, Irma; Maria, Maleeha; Azam, Maleeha; Henkes, Arjen; Blokland, Ellen; Qamar, Raheel; Webster, Andrew R.; Andreasson, Sten; de Baere, Elfride; Bennett, Jean; Chader, Gerald J.; Berger, Wolfgang; Golovleva, Irina; Greenberg, Jacquie; den Hollander, Anneke I.; Klaver, Caroline C.W.; Klevering, B. Jeroen; Lorenz, Birgit; Preising, Markus N.; Ramsear, Raj; Roberts, Lisa; Roepman, Ronald; Rohrschneider, Klaus; Wissinger, Bernd

    2014-01-01

    To investigate the prevalence of sequence variants in LCA5 in patients with Leber congenital amaurosis (LCA), early onset rod-cone dystrophy (EORD) and autosomal recessive retinitis pigmentosa (RP), to delineate the ocular phenotypes, and to provide an overview of all published LCA5 variants in an online database._Patients underwent standard ophthalmic evaluations after providing informed consent. In selected patients, optical coherence tomography (OCT) and fundus autofluorescence imaging was possible. DNA samples from 797 unrelated patients with LCA and 211 with the various types of RP were screened by Sanger sequence analysis of all LCA5 exons and intron/exon junctions. Some LCA patients were pre-screened by APEX technology or selected based on homozygosity mapping. In silico analyses were performed to assess the pathogenicity of the variants. Segregation analysis was performed where possible. Published and novel LCA5 variants were collected, amended for their correct nomenclature, and listed in a Leiden Open Variation Database (LOVD). Sequence analysis identified 18 new probands with 19 different LCA5 variants. Seventeen of the 19 LCA5 variants were novel. Except for two missense variants and one splice site variant, all variants were protein-truncating mutations. Most patients expressed a severe phenotype, typical of LCA. However, some LCA subjects had better vision and intact inner segment/outer segment (IS/OS) junctions on OCT imaging. In two families with LCA5 variants, the phenotype was more compatible with EORD with affected individuals displaying preserved islands of RPE. One of these milder families harbored a homozygous splice site mutation, a second family was found to have a combination of a stop mutation and a missense mutation. This is the largest LCA5 study to date. We sequenced 1008 patients (797 with LCA, 211 with arRP) and identified 18 probands with LCA5 mutations. Mutations in LCA5 are a rare cause of childhood retinal dystrophy accounting for

  11. Reduced Field-of-View Diffusion Tensor Imaging of the Optic Nerve in Retinitis Pigmentosa at 3T.

    PubMed

    Zhang, Y; Guo, X; Wang, M; Wang, L; Tian, Q; Zheng, D; Shi, D

    2016-08-01

    Diffusion tensor imaging may reflect pathology of the optic nerve; however, the ability of DTI to evaluate alterations of the optic nerve in retinitis pigmentosa has not yet been assessed, to our knowledge. The aim of this study was to investigate the diagnostic potential of reduced FOV-DTI in optic neuropathy of retinitis pigmentosa at 3T. Thirty-eight patients and thirty-five healthy controls were enrolled in this study. Measures of visual field and visual acuity of both eyes in all subjects were performed. A reduced FOV-DTI sequence was used to derive fractional anisotropy, apparent diffusion coefficient, principal eigenvalue, and orthogonal eigenvalue of the individual optic nerves. Mean fractional anisotropy, ADC, and eigenvalue maps were obtained for quantitative analysis. Further analyses were performed to determine the correlation of fractional anisotropy, ADC, principal eigenvalue, and orthogonal eigenvalue with optic nerves in patients with mean deviation of the visual field and visual acuity, respectively. The optic nerves of patients with retinitis pigmentosa compared with control subjects showed significantly higher ADC, principal eigenvalue, and orthogonal eigenvalue and significantly lower fractional anisotropy (P < .01). For patients with retinitis pigmentosa, the mean deviation of the visual field of the optic nerve was significantly correlated with mean fractional anisotropy (r = 0.364, P = .001) and orthogonal eigenvalue (r = -0.254, P = .029), but it was not correlated with mean ADC (P = .154) and principal eigenvalue (P = .337). Moreover, no correlation between any DTI parameter and visual acuity in patients with retinitis pigmentosa was observed (P > .05). Reduced FOV-DTI measurement of the optic nerve may serve as a biomarker of axonal and myelin damage in optic neuropathy for patients with retinitis pigmentosa. © 2016 by American Journal of Neuroradiology.

  12. Characterization and mapping of the human rhodopsin kinase gene and screening of the gene for mutations in patients with retinitis pigmentosa

    SciTech Connect

    Khani, S.C.; Lin, D.; Magovcevic, I.

    1994-09-01

    Rhodopsin kinase (RK) is a cytosolic enzyme in rod photoreceptors that initiates the deactivation of the phototransductions cascade by phosphorylating photoactivated rhodopsin. Although the cDNA sequence of bovine RK has been determined previously, no human cDNA or genomic sequence has thus far been available for genetic studies. In order to investigate the possible role of this candidate gene in retinitis pigmentosa (RP) and allied diseases, we have isolated and characterized human cDNA and genomic clones derived from the RK locus. The coding sequence of the human gene is 1692 nucleotides in length and is split into seven exons. The human and the bovine sequence show 84% identity at the nucleotide level and 92% identity at the amino acid level. Thus far, the intronic sequences flanking each exon except for one have been determined. We have also mapped the human RK gene to chromosome 13q34 using fluorescence in situ hybridization. To our knowledge, no RP gene has as yet been linked to this region. However, since the substrate for RK (rhodopsin) and other members of the phototransduction cascade have been implicated in the pathogenesis of RP, it is conceivable that defects in RK can also cause some forms of this disease. We are evaluating this possibility by screening DNA from 173 patients with autosomal recessive RP and 190 patients with autosomal dominant RP. So far, we have found 11 patients with variant bands. In one patient with autosomal dominant RP we discovered the missense change Ser536Leu. Cosegregation studies and further sequencing of the variant bands are currently underway.

  13. Contribution of SNRNP200 sequence variations to retinitis pigmentosa

    PubMed Central

    Zhang, X; Lai, T YY; Chiang, S WY; Tam, P OS; Liu, D TL; Chan, C KM; Pang, C P; Zhao, C; Chen, L J

    2013-01-01

    Purpose Mutations in the SNRNP200 gene have been reported to cause autosomal dominant retinitis pigmentosa (adRP). In this study, we evaluate the mutation profile of SNRNP200 in a cohort of southern Chinese RP patients. Methods Twenty adRP patients from 11 families and 165 index patients with non-syndromic RP with mixed inheritance patterns were screened for mutations in the mutation hotspots of SNRNP200. These included exons 12–16, 22–32, and 38–45, which covered the two helicase ATP-binding domains in DEAD-box and two sec-63 domains. The targeted regions were amplified by polymerase chain reaction and analyzed by direct DNA sequencing, followed by in silico analyses. Results Totally 26 variants were identified, 18 of which were novel. Three non-synonymous variants (p.C502R, p.R1779H and p.I698V) were found exclusively in patients. Two of them, p.C502R and p.R1779H, were each identified in one simplex RP patient, whereas p.I698V occurred in one patient with unknown inheritance pattern. All three residues are highly conserved in SNRNP200 orthologs. Nevertheless, only p.C502R and p.R1779H were predicted to affect protein function by in silico analyses, suggesting these two variants are likely to be disease-causing mutations. Notably, all mutations previously identified in other study populations were not detected in this study. Conclusions Our results reveal a distinct mutation profile of the SNRNP200 gene in a southern Chinese cohort of RP patients. The identification of two novel candidate mutations in two respective patients affirmed that SNRNP200 contributes to a proportion of overall RP. PMID:23887765

  14. Blindness and visual impairment in retinitis pigmentosa: a Cameroonian hospital-based study

    PubMed Central

    Eballe, André Omgbwa; Koki, Godefroy; Emche, Claude Bernard; Bella, Lucienne Assumpta; Kouam, Jeanne Mayouego; Melong, Justin

    2010-01-01

    Aim: We performed a retrospective, analytical study in February 2010 on all retinitis pigmentosa cases seen during ophthalmologic consultation at the Gyneco-Obstetrics and Pediatric Hospital of Yaounde between March 2002 and December 2009 (82 months). The aim of this research was to determine the significance of blindness and visual impairment associated with retinitis pigmentosa in Cameroon. Results: Forty cases were reported, corresponding to a hospital prevalence of 1.6/1000 (21 men and 19 women). The average age of the patients was 43.3 ± 18 years, ranging between 6 and 74 years. Bilateral blindness and low vision was noted in 30% and 27.5% of patients, respectively. The average age of patients with low vision was 40.38 ± 16.27 years and the average age of those with bilateral blindness was 51.08 ± 15.79 years. Retinitis pigmentosa was bilateral in all cases and isolated (without any eye or general additional disease) in 67.5% of cases. Conclusion: Visual impairment is common and becomes even more severe with aging. Patients should be screened to enable them to benefit from management focusing on both appropriate treatment and genetic counseling. PMID:20689779

  15. Patient-specific iPSC-derived photoreceptor precursor cells as a means to investigate retinitis pigmentosa

    PubMed Central

    Tucker, Budd A; Mullins, Robert F; Streb, Luan M; Anfinson, Kristin; Eyestone, Mari E; Kaalberg, Emily; Riker, Megan J; Drack, Arlene V; Braun, Terry A; Stone, Edwin M

    2013-01-01

    Next-generation and Sanger sequencing were combined to identify disease-causing USH2A mutations in an adult patient with autosomal recessive RP. Induced pluripotent stem cells (iPSCs), generated from the patient’s keratinocytes, were differentiated into multi-layer eyecup-like structures with features of human retinal precursor cells. The inner layer of the eyecups contained photoreceptor precursor cells that expressed photoreceptor markers and exhibited axonemes and basal bodies characteristic of outer segments. Analysis of the USH2A transcripts of these cells revealed that one of the patient’s mutations causes exonification of intron 40, a translation frameshift and a premature stop codon. Western blotting revealed upregulation of GRP78 and GRP94, suggesting that the patient’s other USH2A variant (Arg4192His) causes disease through protein misfolding and ER stress. Transplantation into 4-day-old immunodeficient Crb1−/− mice resulted in the formation of morphologically and immunohistochemically recognizable photoreceptor cells, suggesting that the mutations in this patient act via post-developmental photoreceptor degeneration. DOI: http://dx.doi.org/10.7554/eLife.00824.001 PMID:23991284

  16. Oliver-McFarlane syndrome in a chinese boy: retinitis pigmentosa, trichomegaly, hair anomalies and mental retardation.

    PubMed

    Sheng, Xunlun; Zhang, Shuang; Peter Boergen, Klaus; Li, Huiping; Liu, Yani

    2015-03-01

    We report a male patient with retinitis pigmentosa, growth failure, long eyelashes, and sparse hair, which are typical signs of Oliver-McFarlane syndrome. The patient was born to healthy parents and developed night blindness at 2 years of age. Retinitis pigmentosa was diagnosed when he was 5 years old. To date, only 11 cases of Oliver-McFarlane syndrome have been documented, with the present case being the 12th overall and the first in China. Thus, the existence of typical Oliver-McFarlane syndrome in Asians was verified.

  17. Good Epidemiologic Practice in Retinitis Pigmentosa: From Phenotyping to Biobanking

    PubMed Central

    Chizzolini, Marzio; Galan, Alessandro; Milan, Elisabeth; Sebastiani, Adolfo; Costagliola, Ciro; Parmeggiani, Francesco

    2011-01-01

    Inherited retinal dystrophies, such as retinitis pigmentosa (RP), include a group of relatively rare hereditary diseases caused by mutations in genes that code for proteins involved in the maintenance and function of the photoreceptor cells (cones and rods). The different forms of RP consist of progressive neurodegenerative disorders which are generally related to various and severe limitations of visual performances. In the course of typical RP (rod-cone dystrophy), the affected individuals first experience night-blindness and/or visual field constriction (secondary to rod dysfunctions), followed by variable alterations of the central vision (due to cone damages). On the other hand, during the atypical form of RP (cone-rod dystrophy), the cone’s functionalities are prevalently disrupted in comparison with the rod’s ones. The basic diagnosis of RP relies upon the documentation of unremitting loss in photoreceptor activity by electroretinogram and/or visual field testing. The prevalence of all RP typologies is variably reported in about one case for each 3000-5000 individuals, with a total of about two millions of affected persons worldwide. The inherited retinal dystrophies are sometimes the epiphenomenon of a complex framework (syndromic RP), but more often they represent an isolated disorder (about 85-90 % of cases). Although 200 causative RP mutations have been hitherto detected in more than 100 different genes, the molecular defect is identifiable in just about the 50% of the analyzed patients with RP. Not only the RP genotypes are very heterogeneous, but also the patients with the same mutation can be affected by different phenotypic manifestations. RP can be inherited as autosomal dominant, autosomal recessive or X-linked trait, and many sporadic forms are diagnosed in patients with no affected relatives. Dissecting the clinico-genetic complexity of RP has become an attainable objective by means of large-scale research projects, in which the collaboration

  18. Eplerenone, a new treatment for an old problem: Retinitis pigmentosa with recalcitrant macular edema.

    PubMed

    Campos Polo, R; Rubio Sánchez, C; García Guisado, D M; Díaz Luque, M J

    2017-06-14

    The case involves a 35-year-old man, with a history of retinitis pigmentosa, who presented with a bilateral cystoid macular oedema associated with bilateral epiretinal membrane, which was resistant to treatment with oral acetazolamide and intravitreal bevacizumab. The treatment with oral eplerenone was able to improve the visual acuity and macular thickness of this patient. A variety of treatments have been proposed for the management of cystoid macular oedema, associated with retinitis pigmentosa, with variable results. The treatment with oral eplerenone might be a good option for the control of this condition. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Structure-Function Modeling of Optical Coherence Tomography and Standard Automated Perimetry in the Retina of Patients with Autosomal Dominant Retinitis Pigmentosa.

    PubMed

    Smith, Travis B; Parker, Maria; Steinkamp, Peter N; Weleber, Richard G; Smith, Ning; Wilson, David J

    2016-01-01

    To assess relationships between structural and functional biomarkers, including new topographic measures of visual field sensitivity, in patients with autosomal dominant retinitis pigmentosa. Spectral domain optical coherence tomography line scans and hill of vision (HOV) sensitivity surfaces from full-field standard automated perimetry were semi-automatically aligned for 60 eyes of 35 patients. Structural biomarkers were extracted from outer retina b-scans along horizontal and vertical midlines. Functional biomarkers were extracted from local sensitivity profiles along the b-scans and from the full visual field. These included topographic measures of functional transition such as the contour of most rapid sensitivity decline around the HOV, herein called HOV slope for convenience. Biomarker relationships were assessed pairwise by coefficients of determination (R2) from mixed-effects analysis with automatic model selection. Structure-function relationships were accurately modeled (conditional R(2)>0.8 in most cases). The best-fit relationship models and correlation patterns for horizontally oriented biomarkers were different than vertically oriented ones. The structural biomarker with the largest number of significant functional correlates was the ellipsoid zone (EZ) width, followed by the total photoreceptor layer thickness. The strongest correlation observed was between EZ width and HOV slope distance (marginal R(2) = 0.85, p<10(-10)). The mean sensitivity defect at the EZ edge was 7.6 dB. Among all functional biomarkers, the HOV slope mean value, HOV slope mean distance, and maximum sensitivity along the b-scan had the largest number of significant structural correlates. Topographic slope metrics show promise as functional biomarkers relevant to the transition zone. EZ width is strongly associated with the location of most rapid HOV decline.

  20. Structure-Function Modeling of Optical Coherence Tomography and Standard Automated Perimetry in the Retina of Patients with Autosomal Dominant Retinitis Pigmentosa

    PubMed Central

    Smith, Travis B.; Parker, Maria; Steinkamp, Peter N.; Weleber, Richard G.; Smith, Ning; Wilson, David J.

    2016-01-01

    Purpose To assess relationships between structural and functional biomarkers, including new topographic measures of visual field sensitivity, in patients with autosomal dominant retinitis pigmentosa. Methods Spectral domain optical coherence tomography line scans and hill of vision (HOV) sensitivity surfaces from full-field standard automated perimetry were semi-automatically aligned for 60 eyes of 35 patients. Structural biomarkers were extracted from outer retina b-scans along horizontal and vertical midlines. Functional biomarkers were extracted from local sensitivity profiles along the b-scans and from the full visual field. These included topographic measures of functional transition such as the contour of most rapid sensitivity decline around the HOV, herein called HOV slope for convenience. Biomarker relationships were assessed pairwise by coefficients of determination (R2) from mixed-effects analysis with automatic model selection. Results Structure-function relationships were accurately modeled (conditional R2>0.8 in most cases). The best-fit relationship models and correlation patterns for horizontally oriented biomarkers were different than vertically oriented ones. The structural biomarker with the largest number of significant functional correlates was the ellipsoid zone (EZ) width, followed by the total photoreceptor layer thickness. The strongest correlation observed was between EZ width and HOV slope distance (marginal R2 = 0.85, p<10−10). The mean sensitivity defect at the EZ edge was 7.6 dB. Among all functional biomarkers, the HOV slope mean value, HOV slope mean distance, and maximum sensitivity along the b-scan had the largest number of significant structural correlates. Conclusions Topographic slope metrics show promise as functional biomarkers relevant to the transition zone. EZ width is strongly associated with the location of most rapid HOV decline. PMID:26845445

  1. Nonallelic heterogeneity in autosomal dominant retinitis pigmentosa with incomplete penetrance

    SciTech Connect

    Kim, S.K.; Berson, E.L.; Dryja, T.P.

    1994-08-01

    Retinitis pigmentosa is a group of retinal diseases in which photoreceptor cells throughout the retina degenerate. Although there is considerable genetic heterogeneity (autosomal dominant, autosomal recessive, and X-linked forms exist), there is a possibility that some clinically defined subtypes of the disease may be the result of mutations at the same locus. One possible clinically defined subtype is that of autosomal dominant retinitis pigmentosa (ADRP) with incomplete penetrance. Whereas in most families with ADRP, carriers can be clearly identified because of visual loss, ophthalmological findings, or abnormal electroretinograms (ERGs), in occasional families some obligate carriers are asymptomatic and have normal or nearly normal ERGs even late in life. A recent paper reported the mapping of the diseases locus in one pedigree (designated adRP7) with ADRP with incomplete penetrance to chromosome 7p. To test the idea that ADRP with incomplete penetrance may be genetically homogeneous, we have evaluated whether a different family with incomplete penetrance also has a disease gene linked to the same region. 4 refs., 1 fig., 1 tab.

  2. Whole-exome sequencing identifies novel compound heterozygous mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa

    PubMed Central

    Méndez-Vidal, Cristina; González-del Pozo, María; Vela-Boza, Alicia; Santoyo-López, Javier; López-Domingo, Francisco J.; Vázquez-Marouschek, Carmen; Dopazo, Joaquin; Borrego, Salud

    2013-01-01

    Purpose Retinitis pigmentosa (RP) is an inherited retinal dystrophy characterized by extreme genetic and clinical heterogeneity. Thus, the diagnosis is not always easily performed due to phenotypic and genetic overlap. Current clinical practices have focused on the systematic evaluation of a set of known genes for each phenotype, but this approach may fail in patients with inaccurate diagnosis or infrequent genetic cause. In the present study, we investigated the genetic cause of autosomal recessive RP (arRP) in a Spanish family in which the causal mutation has not yet been identified with primer extension technology and resequencing. Methods We designed a whole-exome sequencing (WES)-based approach using NimbleGen SeqCap EZ Exome V3 sample preparation kit and the SOLiD 5500×l next-generation sequencing platform. We sequenced the exomes of both unaffected parents and two affected siblings. Exome analysis resulted in the identification of 43,204 variants in the index patient. All variants passing filter criteria were validated with Sanger sequencing to confirm familial segregation and absence in the control population. In silico prediction tools were used to determine mutational impact on protein function and the structure of the identified variants. Results Novel Usher syndrome type 2A (USH2A) compound heterozygous mutations, c.4325T>C (p.F1442S) and c.15188T>G (p.L5063R), located in exons 20 and 70, respectively, were identified as probable causative mutations for RP in this family. Family segregation of the variants showed the presence of both mutations in all affected members and in two siblings who were apparently asymptomatic at the time of family ascertainment. Clinical reassessment confirmed the diagnosis of RP in these patients. Conclusions Using WES, we identified two heterozygous novel mutations in USH2A as the most likely disease-causing variants in a Spanish family diagnosed with arRP in which the cause of the disease had not yet been identified with

  3. Association Between Aqueous Flare and Epiretinal Membrane in Retinitis Pigmentosa.

    PubMed

    Fujiwara, Kohta; Ikeda, Yasuhiro; Murakami, Yusuke; Nakatake, Shunji; Tachibana, Takashi; Yoshida, Noriko; Nakao, Shintaro; Hisatomi, Toshio; Yoshida, Shigeo; Yoshitomi, Takeshi; Sonoda, Koh-Hei; Ishibashi, Tatsuro

    2016-08-01

    Epiretinal membrane (ERM) is a frequent macular complication in patients with retinitis pigmentosa (RP). The etiology of ERM formation in RP is largely unknown. The purpose of this study was to investigate the association between aqueous flare, a surrogate index of intraocular inflammation, and ERM secondary to RP. We retrospectively studied a total of 206 eyes of 117 patients who were diagnosed with typical RP. Aqueous flare values were measured consecutively in 2012 and 2013 using a laser flare cell meter. Spectral-domain optical coherence tomography images and fundus photographs taken on the same day of the aqueous flare measurements were analyzed for ERM detection. The mean values of aqueous flare, age, and frequency of male sex were significantly higher in the RP patients with ERM compared with the RP patients without ERM (P < 0.0001, P = 0.007, and P = 0.004, respectively). After adjustment for age and sex, the eyes in the highest quartile of aqueous flare had significantly higher odds of having ERM than those in the lowest quartile (odds ratio [OR], 2.68; 95% confidence interval [CI], 1.04-6.93), and the linear trend across flare levels was significant (P = 0.005). In addition, each 1-log-transformed increase in flare values was associated with an elevation of the likelihood of having ERM (OR, 2.59; 95% CI, 1.33-5.06). Our analysis demonstrated that elevated aqueous flare is associated with ERM secondary to RP, suggesting that inflammation may be implicated in the pathogenesis of ERM formation in RP.

  4. Gene Augmentation for X-Linked Retinitis Pigmentosa Caused by Mutations in RPGR

    PubMed Central

    Beltran, William A.; Cideciyan, Artur V.; Lewin, Alfred S.; Hauswirth, William W.; Jacobson, Samuel G.; Aguirre, Gustavo D.

    2015-01-01

    X-linked retinitis pigmentosa (XLRP) caused by mutations in the RPGR gene is a severe and early onset form of retinal degeneration, and no treatment is currently available. Recent evidence in two clinically relevant canine models shows that adeno-associated viral (AAV)-mediated RPGR gene transfer to rods and cones can prevent disease onset and rescue photoreceptors at early- and mid-stages of degeneration. There is thus a strong incentive for conducting long-term, preclinical efficacy and safety studies, while concomitantly pursuing the detailed phenotypic characterization of XLRP disease in patients that may benefit from such corrective therapy. PMID:25301933

  5. Gene therapy in animal models of autosomal dominant retinitis pigmentosa.

    PubMed

    Rossmiller, Brian; Mao, Haoyu; Lewin, Alfred S

    2012-01-01

    Gene therapy for dominantly inherited genetic disease is more difficult than gene-based therapy for recessive disorders, which can be treated with gene supplementation. Treatment of dominant disease may require gene supplementation partnered with suppression of the expression of the mutant gene either at the DNA level, by gene repair, or at the RNA level by RNA interference or transcriptional repression. In this review, we examine some of the gene delivery approaches used to treat animal models of autosomal dominant retinitis pigmentosa, focusing on those models associated with mutations in the gene for rhodopsin. We conclude that combinatorial approaches have the greatest promise for success.

  6. Gene therapy in animal models of autosomal dominant retinitis pigmentosa

    PubMed Central

    Rossmiller, Brian; Mao, Haoyu

    2012-01-01

    Gene therapy for dominantly inherited genetic disease is more difficult than gene-based therapy for recessive disorders, which can be treated with gene supplementation. Treatment of dominant disease may require gene supplementation partnered with suppression of the expression of the mutant gene either at the DNA level, by gene repair, or at the RNA level by RNA interference or transcriptional repression. In this review, we examine some of the gene delivery approaches used to treat animal models of autosomal dominant retinitis pigmentosa, focusing on those models associated with mutations in the gene for rhodopsin. We conclude that combinatorial approaches have the greatest promise for success. PMID:23077406

  7. A Family of Congenital Hepatic Fibrosis and Atypical Retinitis Pigmentosa.

    PubMed

    Pawar, Sunil; Zanwar, Vinay; Mohite, Ashok; Surude, Ravindra; Rathi, Pravin; Balasubramani, Meenakshi

    2015-11-05

    Congenital hepatic fibrosis is a rare cause of portal hypertension and esophageal varices in children. We report cases of siblings with biopsy proven congenital hepatic fibrosis and with atypical retinitis pigmentosa. They presented with repeated episodes of jaundice along with progressive decrease of vision in night. They had hepatosplenomegaly and portal hypertension with esophageal varices. One of the siblings had a large regenerating nodule replacing the entire right lobe of the liver and other one developed repeated hematemesis. This constellation of diagnosis belongs to the ciliopathy group of disorders. The spectrum of ciliopathy disorders has been evolving, and it varies from mild to severe manifestations.

  8. Posterior microphthalmos, retinitis pigmentosa and optic disc drusen with white dots. A case report.

    PubMed

    Plaza, P; Iturralde, O; Abascal, C

    2017-05-13

    To present the case of a patient with a posterior microphthalmos-optic disc drusen-retinitis pigmentosa syndrome associated, for the first time, with white dots in the posterior pole. The posterior microphthalmos, retinitis pigmentosa and optic disc drusen syndrome was described for the first time in literature in 1991. Later, it was associated with a pattern of foveal thickening and/or foveoschisis. Different forms of mutations on chromosomes 11 and 14 have been identified as being responsible for the appearance of this syndrome, but the inheritance pattern is unknown. The case is reported of a 37 year-old man, with no personal or family history of interest, diagnosed with this syndrome in association with white dots in the posterior pole. Such a morphological association has never been published before in literature. The posterior microphthalmos, retinitis pigmentosa and optic disc drusen syndrome is a very rare entity, and has never been described associated with white dots in the posterior pole. More case reports are needed to establish clear patterns of both the disease and inheritance. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. The mechanism of cone cell death in Retinitis Pigmentosa.

    PubMed

    Campochiaro, Peter A; Mir, Tahreem A

    2017-09-27

    Retinitis Pigmentosa (RP) is a group of diseases in which one of a large number of mutations causes death of rod photoreceptors. After rods die, cone photoreceptors slowly degenerate in a characteristic pattern. The mechanism of rod cell death varies depending upon the gene that is mutated and the rate that rods degenerate is an important prognostic feature, because cones do not begin to degenerate until almost all rods have been eliminated. Rod cell death causes night blindness, but visual disability and blindness result from cone degeneration and therefore it is critical to determine the mechanisms by which it occurs. The death of rods reduces oxygen consumption resulting in high tissue levels of oxygen in the outer retina. The excess oxygen stimulates superoxide radical production by mismatches in the electron transport chain in mitochondria and by stimulation of NADPH oxidase activity in cytoplasm. The high levels of superoxide radicals overwhelm the antioxidant defense system and generate more reactive species including peroxynitrite which is extremely damaging and difficult to detoxify. This results in progressive oxidative damage in cones which contributes to cone cell death and loss of function because drugs or gene transfer that reduce oxidative stress promote cone survival and maintenance of function. Compared with aqueous humor samples from control patients, those from patients with RP show significant elevation of carbonyl content on proteins indicating oxidative damage and a reduction in the ratio of reduced to oxidized glutathione indicating depletion of a major component of the antioxidant defense system from ongoing oxidative stress. The first step in clinical trials will be to identify doses of therapeutic agents that reverse these biomarkers of disease to assist in design of much longer trials with functional and anatomic endpoints. Copyright © 2017. Published by Elsevier Ltd.

  10. EDI-OCT evaluation of choroidal thickness in retinitis pigmentosa.

    PubMed

    Sodi, Andrea; Lenzetti, Chiara; Murro, Vittoria; Caporossi, Orsola; Mucciolo, Dario P; Bacherini, Daniela; Cipollini, Francesca; Passerini, Ilaria; Virgili, Gianni; Rizzo, Stanislao

    2017-06-09

    To evaluate choroidal thickness (CT) in retinitis pigmentosa (RP) using enhanced depth imaging (EDI) optical coherence tomography (OCT). A retrospective analysis of a group of patients with RP who underwent EDI-OCT was performed. Choroidal thickness measurements were compared with those of age- and sex-matched healthy subjects. In the RP group, the possible association between subfoveal CT and some clinical parameters (visual acuity, age, age at disease onset, duration of the disease, macular thickness, visual field loss, electroretinography [ERG]) was evaluated. The study recruited 39 patients with RP with an average age of 43.3 ± 11.3 years while the control group consisted of 73 healthy subjects with an average age of 42.9 ± 12.10 years. On average, CT was significantly thinner in the RP group compared to the controls (p<0.0001). In the RP group, we could not find any significant association between CT and the considered clinical parameters even if there was a trend for decreasing CT with increasing age (r = -0.23, p = 0.096). In the control group, subfoveal CT showed a slightly significant correlation with age (r = -0.21, p = 0.04) but not with macular thickness and visual acuity. In our series, CT was significantly lower in the RP group in comparison with the controls, as measured by EDI-OCT, but did not correlate with age, age at onset, duration of the disease, macular thickness, visual acuity, visual field loss, or ERG responses. Although the clinical implications of choroidal changes in RP have not yet been clearly determined, the evaluation of choroidal features may provide information that could be useful to clarify the pathophysiology of the disease.

  11. A novel mutation in retinitis pigmentosa GTPase regulator gene with a distinctive retinitis pigmentosa phenotype in a Chinese family.

    PubMed

    Sheng, Xunlun; Li, Zili; Zhang, Xinfang; Wang, Jing; Ren, Hongwang; Sun, Yanbo; Meng, Ruihua; Rong, Weining; Zhuang, Wenjuan

    2010-08-15

    To screen the mutation in the retinitis pigmentosa GTPase regulator (RPGR) ORF15 in a large Chinese family with X-linked recessive retinitis pigmentosa and describe the phenotype in affected male and female carriers. Ophthalmic examination was performed on 77 family members to identify affected individuals and to characterize the disease phenotype. PCR and direct sequencing were used for screening mutations in the RPGR gene. Mutation screening demonstrated a novel mutation ORF15+577_578 delAG, which caused an open reading frameshift and resulted in premature truncation of the RPGR protein. The mutation was detected in eight affected male individuals and 14 obligate female carriers of the family and was found to segregate with the phenotype in this family. The mutation led to a severe retinitis pigmentosa (RP) phenotype in male-affected individuals, with some variability in the age of onset of night blindness and visual acuity, but was recessive in female carriers without an RP phenotype. However, the state associated with the carrier was moderate to high myopia with the refractive error ranging from -5.00 D to 22.00 D in 14 female carriers. This novel mutation in RPGR ORF15 causes a serious RP phenotype in males and no RP phenotype in female carriers. Moderate to high myopia was a particular feature for female carriers in this pedigree. Our finding expands the spectrum of RPGR mutations causing X-linked RP and expands phenotypic spectrum of the disease in a Chinese family. This finding will be useful for further genetic consultations and genetic diagnosis.

  12. A novel mutation in retinitis pigmentosa GTPase regulator gene with a distinctive retinitis pigmentosa phenotype in a Chinese family

    PubMed Central

    Zhang, Xinfang; Wang, Jing; Ren, Hongwang; Sun, Yanbo; Meng, Ruihua; Rong, Weining

    2010-01-01

    Purpose To screen the mutation in the retinitis pigmentosa GTPase regulator (RPGR) ORF15 in a large Chinese family with X-linked recessive retinitis pigmentosa and describe the phenotype in affected male and female carriers. Methods Ophthalmic examination was performed on 77 family members to identify affected individuals and to characterize the disease phenotype. PCR and direct sequencing were used for screening mutations in the RPGR gene. Results Mutation screening demonstrated a novel mutation ORF15+577_578 delAG, which caused an open reading frameshift and resulted in premature truncation of the RPGR protein. The mutation was detected in eight affected male individuals and 14 obligate female carriers of the family and was found to segregate with the phenotype in this family. The mutation led to a severe retinitis pigmentosa (RP) phenotype in male-affected individuals, with some variability in the age of onset of night blindness and visual acuity, but was recessive in female carriers without an RP phenotype. However, the state associated with the carrier was moderate to high myopia with the refractive error ranging from −5.00 D to 22.00 D in 14 female carriers. Conclusions This novel mutation in RPGR ORF15 causes a serious RP phenotype in males and no RP phenotype in female carriers. Moderate to high myopia was a particular feature for female carriers in this pedigree. Our finding expands the spectrum of RPGR mutations causing X-linked RP and expands phenotypic spectrum of the disease in a Chinese family. This finding will be useful for further genetic consultations and genetic diagnosis. PMID:20806050

  13. [Research progress of treatment strategies for retinitis pigmentosa].

    PubMed

    Qian, T W; Xu, X

    2017-02-11

    Retinitis pigmentosa (RP) is a genetically heterogeneous group of hereditary retinal disorders characterized by photoreceptor cell death, associated with night blindness, vision loss, progressive peripheral visual field loss and abnormalities in the electroretinogram. A number of gene defects have so far been associated with RP, which cause a progressive loss of rod photoreceptor function, followed by cone photoreceptor dysfunction and eventually complete blindness. The rate of blindness related to RP is high. At present there is no effective therapeutic strategy for RP. In recent years, with the progress of molecular biology technique, many new therapeutic approaches have become promising. This article summarizes the pathogenesis of RP and gives a brief overview of related research progress of RP therapeutic strategies. (Chin J Ophthalmol, 2017, 53: 148-153).

  14. Two-Step Reactivation of Dormant Cones in Retinitis Pigmentosa

    PubMed Central

    Wang, Wei; Lee, Sang Joon; Scott, Patrick A.; Lu, Xiaoqin; Emery, Douglas; Liu, Yongqin; Ezashi, Toshihiko; Roberts, Michael R.; Ross, Jason W.; Kaplan, Henry J.; Dean, Douglas C.

    2016-01-01

    Most Retinitis Pigmentosa (RP) mutations arise in rod photoreceptor genes, leading to diminished peripheral and nightime vision. Using a pig model of autosomal-dominant RP, we show glucose becomes sequestered in the retinal pigment epithelium (RPE), and thus is not transported to photoreceptors. The resulting starvation for glucose metabolites impairs synthesis of cone visual pigment -rich outer segments (OS), and then their mitochondrial-rich inner segments dissociate. Loss of these functional structures diminishes cone-dependent high-resolution central vision, which is utilized for most daily tasks. By transplanting wild-type rods, to restore glucose transport, or directly replacing glucose in the subretinal space, to bypass its retention in the RPE, we can regenerate cone functional structures, reactivating the dormant cells. Beyond providing metabolic building blocks for cone functional structures, we show glucose induces thioredoxin-interacting protein (Txnip) to regulate Akt signaling, thereby shunting metabolites toward aerobic glucose metabolism and regenerating cone OS synthesis. PMID:27050517

  15. Retinitis Pigmentosa with EYS Mutations Is the Most Prevalent Inherited Retinal Dystrophy in Japanese Populations

    PubMed Central

    Arai, Yuuki; Maeda, Akiko; Hirami, Yasuhiko; Ishigami, Chie; Kosugi, Shinji; Mandai, Michiko; Kurimoto, Yasuo; Takahashi, Masayo

    2015-01-01

    The aim of this study was to gain information about disease prevalence and to identify the responsible genes for inherited retinal dystrophies (IRD) in Japanese populations. Clinical and molecular evaluations were performed on 349 patients with IRD. For segregation analyses, 63 of their family members were employed. Bioinformatics data from 1,208 Japanese individuals were used as controls. Molecular diagnosis was obtained by direct sequencing in a stepwise fashion utilizing one or two panels of 15 and 27 genes for retinitis pigmentosa patients. If a specific clinical diagnosis was suspected, direct sequencing of disease-specific genes, that is, ABCA4 for Stargardt disease, was conducted. Limited availability of intrafamily information and decreasing family size hampered identifying inherited patterns. Differential disease profiles with lower prevalence of Stargardt disease from European and North American populations were obtained. We found 205 sequence variants in 159 of 349 probands with an identification rate of 45.6%. This study found 43 novel sequence variants. In silico analysis suggests that 20 of 25 novel missense variants are pathogenic. EYS mutations had the highest prevalence at 23.5%. c.4957_4958insA and c.8868C>A were the two major EYS mutations identified in this cohort. EYS mutations are the most prevalent among Japanese patients with IRD. PMID:26161267

  16. [Study on treatment of retinitis pigmentosa with traditional Chinese medicine by Flicker electroretinogram].

    PubMed

    Wu, X W; Tang, Y Z

    1996-06-01

    Study on treatment of 54 patients (106 eyes) of retinitis pigmentosa (RP) with traditional Chinese medicine was conducted by using modified method of electroretinography. Results showed: (1) Flicker response of electroretinogram was the most sensitive-criterion in examination, it was more effective when combined with infrared spectrogram. (2) The 30 Hz flicker index, response time were improved after TCM therapy in different hereditary types of RP, the improvement was significant in patients with Yang-Deficiency of Spleen-Kidney Syndrome and those of autosomal dominant inheritance type (P < 0.01). (3) Decrease of phase angle (phi) under different frequency of flicker after treatment was also significant statistically. The results suggested that flicker responses, which represents mainly retinal cone activity of patients, could be improved to a certain extent by TCM treatment, even in those with advanced retinal degeneration. TCM treatment could also enhance the bioactivity of nerve network and therefore have a definite significance in retarding the progression of disease and keeping the central vision. The flicker ERG, especially its flicker index, is an effective, sensitive and useful parameter for detection of visual function in patient with retinitis pigmentosa.

  17. Local signaling from a retinal prosthetic in a rodent retinitis pigmentosa model in vivo

    NASA Astrophysics Data System (ADS)

    Fransen, James W.; Pangeni, Gobinda; Pardue, Machelle T.; McCall, Maureen A.

    2014-08-01

    Objective. In clinical trials, retinitis pigmentosa patients implanted with a retinal prosthetic device show enhanced spatial vision, including the ability to read large text and navigate. New prosthetics aim to increase spatial resolution by decreasing pixel/electrode size and limiting current spread. To examine spatial resolution of a new prosthetic design, we characterized and compared two photovoltaic array (PVA) designs and their interaction with the retina after subretinal implantation in transgenic S334ter line 3 rats (Tg S334ter-3). Approach. PVAs were implanted subretinally at two stages of degeneration and assessed in vivo using extracellular recordings in the superior colliculus (SC). Several aspects of this interaction were evaluated by varying duration, irradiance and position of a near infrared laser focused on the PVA. These characteristics included: activation threshold, response linearity, SC signal topography and spatial localization. The major design difference between the two PVA designs is the inclusion of local current returns in the newer design. Main results. When tested in vivo, PVA-evoked response thresholds were independent of pixel/electrode size, but differ between the new and old PVA designs. Response thresholds were independent of implantation age and duration (⩽7.5 months). For both prosthesis designs, threshold intensities were within established safety limits. PVA-evoked responses require inner retina synaptic transmission and do not directly activate retinal ganglion cells. The new PVA design evokes local retinal activation, which is not found with the older PVA design that lacks local current returns. Significance. Our study provides in vivo evidence that prosthetics make functional contacts with the inner nuclear layer at several stages of degeneration. The new PVA design enhances local activation within the retina and SC. Together these results predict that the new design can potentially harness the inherent processing within

  18. LOCAL SIGNALING FROM A RETINAL PROSTHETIC IN A RODENT RETINITIS PIGMENTOSA MODEL IN VIVO

    PubMed Central

    Fransen, James W.; Pangeni, Gobinda; Pardue, Machelle T.; McCall, Maureen A.

    2014-01-01

    Objective In clinical trials, retinitis pigmentosa (RP) patients implanted with a retinal prosthetic device show enhanced spatial vision, including the ability to read large text and navigate. New prosthetics aim to increase spatial resolution by decreasing pixel/electrode size and limiting current spread. To examine spatial resolution of a new prosthetic design, we characterized and compared two photovoltaic array (PVA) designs and their interaction with the retina after subretinal implantation in transgenic S334ter line 3 rats (Tg S334ter-3). Approach PVAs were implanted subretinally at two stages of degeneration and assessed in vivo using extracellular recordings in the superior colliculus (SC). Several aspects of this interaction were evaluated by varying duration, irradiance and position of a near infrared (NIR) laser focused on the PVA. These characteristics included: activation threshold, response linearity, SC signal topography and spatial localization. The major design difference between the two PVA designs is the inclusion of local current returns in the newer design. Main Results When tested in vivo, PVA-evoked response thresholds were independent of pixel/electrode size, but differ between the new and old PVA designs. Response thresholds were independent of implantation age and duration (≤ 7.5 months). For both prosthesis designs, threshold intensities were within established safety limits. PVA-evoked responses require inner retina synaptic transmission and do not directly activate retinal ganglion cells (RGCs). The new PVA design evokes local retinal activation, which is not found with the older PVA design that lacks local current returns. Significance Our study provides in vivo evidence that prosthetics make functional contacts with the inner nuclear layer at several stages of degeneration. The new PVA design enhances local activation within the retina and SC. Together these results predict that the new design can potentially harness the inherent

  19. Relative Difficulties of Daily Living Tasks with Retinitis Pigmentosa.

    PubMed

    Latham, Keziah; Baranian, Mohammad; Timmis, Matthew A; Fisher, Andy; Pardhan, Shahina

    2017-03-01

    To determine the relative difficulty of activity of daily living tasks for people with retinitis pigmentosa (RP). Participants with RP (n = 166) rated the difficulty of tasks (n = 43) underpinning the Dutch Activity Inventory goals of mobility indoors and outdoors, shopping, and using public transport. Demographic characteristics were also determined. Responses were Rasch analyzed to determine properties of the scale, derive unidimensional subscales, and consider differential item functioning (DIF). After removal of one ill-fitting item, the remaining 42 tasks formed a scale with reasonable Rasch parameters but poor unidimensionality. The most difficult tasks were orienting in poor and bright light both indoors and outdoors, and avoiding peripheral obstacles outdoors. Eight subscales were derived with unidimensional properties, each of which could be considered as requiring similar skills. DIF identified that tasks from the "poor light and obstacles" subscale were more difficult for those younger than the median age, nonusers of mobility aids, and those not registered or registered sight impaired. Tasks from the "finding products" and "public transport" subscales were more difficult for those older than the median age, with longer duration of visual loss, users of mobility aids, and those registered severely sight impaired. The most difficult tasks for people with RP of orienting in poor light and avoiding peripheral obstacles are relatively more difficult for those not registered as "severely sight impaired," but are less difficult for those who use mobility aids. Mobility aids (guide dog or cane), therefore, do benefit users in their perceived ability in these particular tasks. The derived unidimensional subscales reorganize the tasks from those grouped together by goal (researcher driven) to those perceived as requiring similar skills by people with RP (patient driven) and can be used as an evidence base for orientation and mobility training protocols.

  20. Mutations in TOPORS cause autosomal dominant retinitis pigmentosa with perivascular retinal pigment epithelium atrophy.

    PubMed

    Chakarova, Christina F; Papaioannou, Myrto G; Khanna, Hemant; Lopez, Irma; Waseem, Naushin; Shah, Amna; Theis, Torsten; Friedman, James; Maubaret, Cecilia; Bujakowska, Kinga; Veraitch, Brotati; Abd El-Aziz, Mai M; Prescott, De Quincy; Parapuram, Sunil K; Bickmore, Wendy A; Munro, Peter M G; Gal, Andreas; Hamel, Christian P; Marigo, Valeria; Ponting, Chris P; Wissinger, Bernd; Zrenner, Eberhart; Matter, Karl; Swaroop, Anand; Koenekoop, Robert K; Bhattacharya, Shomi S

    2007-11-01

    We report mutations in the gene for topoisomerase I-binding RS protein (TOPORS) in patients with autosomal dominant retinitis pigmentosa (adRP) linked to chromosome 9p21.1 (locus RP31). A positional-cloning approach, together with the use of bioinformatics, identified TOPORS (comprising three exons and encoding a protein of 1,045 aa) as the gene responsible for adRP. Mutations that include an insertion and a deletion have been identified in two adRP-affected families--one French Canadian and one German family, respectively. Interestingly, a distinct phenotype is noted at the earlier stages of the disease, with an unusual perivascular cuff of retinal pigment epithelium atrophy, which was found surrounding the superior and inferior arcades in the retina. TOPORS is a RING domain-containing E3 ubiquitin ligase and localizes in the nucleus in speckled loci that are associated with promyelocytic leukemia bodies. The ubiquitous nature of TOPORS expression and a lack of mutant protein in patients are highly suggestive of haploinsufficiency, rather than a dominant negative effect, as the molecular mechanism of the disease and make rescue of the clinical phenotype amenable to somatic gene therapy.

  1. Novel compound heterozygous mutations in CNGA1in a Chinese family affected with autosomal recessive retinitis pigmentosa by targeted sequencing.

    PubMed

    Wang, Min; Gan, Dekang; Huang, Xin; Xu, Gezhi

    2016-07-08

    About 37 genes have been reported to be involved in autosomal recessive retinitis pigmentosa, a hereditary retinal disease. However, causative genes remain unclear in a lot of cases. Two sibs of a Chinese family with ocular disease were diagnosed in Eye and ENT Hospital of Fudan University. Targeted sequencing performed on proband to screen pathogenic mutations. PCR combined Sanger sequencing then performed on eight family members including two affected and six unaffected individuals to determine whether mutations cosegregate with disease. Two affected members exhibited clinical features that fit the criteria of autosomal recessive retinitis pigmentosa. Two heterozygous mutations (NM000087, p.Y82X and p.L89fs) in CNGA1 were revealed on proband. Affected members were compound heterozygotes for the two mutations whereas unaffected members either had no mutation or were heterozygote carriers for only one of the two mutations. That is, these mutations cosegregate with autosomal recessive retinitis pigmentosa. Compound heterozygous mutations (NM000087, p.Y82X and p.L89fs) in exon 6 of CNGA1are pathogenic mutations in this Chinese family. Of which, p.Y82X is firstly reported in patient with autosomal recessive retinitis pigmentosa.

  2. Genetic linkage studies in autosomal recessive retinitis pigmentosa

    SciTech Connect

    Mansfield, D.C.; Teague, P.W.; Barber, A.

    1994-09-01

    Autosomal recessive retinitis pigmentosa (arRP) is a severe retinal dystrophy characterized by night blindness, progressive constriction of the visual fields and loss of central vision in the fourth or fifth decades. The frequency of this form of retinitis pigmentosa (RP) varies in different populations. Mutations within the rhodopsin, cyclic GMP phosphodiesterase-{beta} subunit and cGMP-gated channel genes have been reported in some arRP families. The genetic loci responsible for the majority of cases have yet to be identified. Genetic heterogeneity is likely to be extensive. In order to minimize the amount of genetic heterogenity, a set of arRP families was ascertained within the South-Central Sardinian population, in which 81% of families with a known mode of inheritance show an autosomal recessive form of RP. The Sardinian population is an ethnic {open_quotes}outlier{close_quotes}, having remained relatively isolated from mainland and other cultures. Genetic linkage data has been obtained in a set of 11 Sardinian arRP kindreds containing 26 affected members. Under the assumption of genetic homogeneity, no evidence of linkage was found in the arRP kindreds using 195 markers, which excluded 62% of the genome (Z<-2). Positive lod scores were obtained with D14S80 which showed no recombination in a subset of 5 families. Heterogeneity testing using D14S80 and arRP showed no significant evidence of heterogeneity (p=0.18) but evidence of linkage ({chi}{sup 2}=3.64, p=0.028). We are currently screening the neural retina-specific leucine zipper gene (NRL) in 14q11 for mutations as a candidate locus.

  3. Genomic DNA nanoparticles rescue rhodopsin-associated retinitis pigmentosa phenotype

    PubMed Central

    Han, Zongchao; Banworth, Marcellus J.; Makkia, Rasha; Conley, Shannon M.; Al-Ubaidi, Muayyad R.; Cooper, Mark J.; Naash, Muna I.

    2015-01-01

    Mutations in the rhodopsin gene cause retinal degeneration and clinical phenotypes including retinitis pigmentosa (RP) and congenital stationary night blindness. Effective gene therapies have been difficult to develop, however, because generating precise levels of rhodopsin expression is critical; overexpression causes toxicity, and underexpression would result in incomplete rescue. Current gene delivery strategies routinely use cDNA-based vectors for gene targeting; however, inclusion of noncoding components of genomic DNA (gDNA) such as introns may help promote more endogenous regulation of gene expression. Here we test the hypothesis that inclusion of genomic sequences from the rhodopsin gene can improve the efficacy of rhodopsin gene therapy in the rhodopsin knockout (RKO) mouse model of RP. We utilize our compacted DNA nanoparticles (NPs), which have the ability to transfer larger and more complex genetic constructs, to deliver murine rhodopsin cDNA or gDNA. We show functional and structural improvements in RKO eyes for up to 8 months after NP-mediated gDNA but not cDNA delivery. Importantly, in addition to improvements in rod function, we observe significant preservation of cone function at time points when cones in the RKO model are degenerated. These results suggest that inclusion of native expression elements, such as introns, can significantly enhance gene expression and therapeutic efficacy and may become an essential option in the array of available gene delivery tools.— Han, Z., Banworth, M. J., Makkia, R., Conley, S. M., Al-Ubaidi, M. R., Cooper, M. J., Naash, M. I. Genomic DNA nanoparticles rescue rhodopsin-associated retinitis pigmentosa phenotype. PMID:25713057

  4. Disease mechanisms of X-linked retinitis pigmentosa due to RP2 and RPGR mutations.

    PubMed

    Lyraki, Rodanthi; Megaw, Roly; Hurd, Toby

    2016-10-15

    Photoreceptor degeneration is the prominent characteristic of retinitis pigmentosa (RP), a heterogeneous group of inherited retinal dystrophies resulting in blindness. Although abnormalities in many pathways can cause photoreceptor degeneration, one of the most important causes is defective protein transport through the connecting cilium, the structure that connects the biosynthetic inner segment with the photosensitive outer segment of the photoreceptors. The majority of patients with X-linked RP have mutations in the retinitis pigmentosa GTPase regulator (RPGR) or RP2 genes, the protein products of which are both components of the connecting cilium and associated with distinct mechanisms of protein delivery to the outer segment. RP2 and RPGR proteins are associated with severe diseases ranging from classic RP to atypical forms. In this short review, we will summarise current knowledge generated by experimental studies and knockout animal models, compare and discuss the prominent hypotheses about the two proteins' functions in retinal cell biology. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  5. Randomized trial of ciliary neurotrophic factor delivered by encapsulated cell intraocular implants for retinitis pigmentosa.

    PubMed

    Birch, David G; Weleber, Richard G; Duncan, Jacque L; Jaffe, Glenn J; Tao, Weng

    2013-08-01

    To evaluate the safety and effect on visual function of ciliary neurotrophic factor delivered via an intraocular encapsulated cell implant for the treatment of retinitis pigmentosa (RP). Ciliary neurotrophic factor for late-stage retinitis pigmentosa study 3 (CNTF3; n = 65) and ciliary neurotrophic factor for early-stage retinitis pigmentosa study 4 (CNTF4; n = 68) were multicenter, sham-controlled dose-ranging studies. Patients were randomly assigned to receive a high- or low-dose implant in 1 eye and sham surgery in the fellow eye. The primary endpoints were change in best-corrected visual acuity (BCVA) at 12 months for CNTF3 and change in visual field sensitivity at 12 months for CNTF4. Patients had the choice of retaining or removing the implant at 12 months for CNTF3 and 24 months for CNTF4. There were no serious adverse events related to either the encapsulated cell implant or the surgical procedure. In CNTF3, there was no change in acuity in either ciliary neurotrophic factor- or sham-treated eyes at 1 year. In CNTF4, eyes treated with the high-dose implant showed a significant decrease in sensitivity while no change was seen in sham- and low dose-treated eyes at 12 months. The decrease in sensitivity was reversible upon implant removal. In both studies, ciliary neurotrophic factor treatment resulted in a dose-dependent increase in retinal thickness. Long-term intraocular delivery of ciliary neurotrophic factor is achieved by the encapsulated cell implant. Neither study showed therapeutic benefit in the primary outcome variable. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Molecular genetic analysis of retinitis pigmentosa in Indonesia using genome-wide homozygosity mapping.

    PubMed

    Siemiatkowska, Anna M; Arimadyo, Kentar; Moruz, Luminita M; Astuti, Galuh D N; de Castro-Miro, Marta; Zonneveld, Marijke N; Strom, Tim M; de Wijs, Ilse J; Hoefsloot, Lies H; Faradz, Sultana M H; Cremers, Frans P M; den Hollander, Anneke I; Collin, Rob W J

    2011-01-01

    Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous retinal disorder. Despite tremendous knowledge about the genes involved in RP, little is known about the genetic causes of RP in Indonesia. Here, we aim to identify the molecular genetic causes underlying RP in a small cohort of Indonesian patients, using genome-wide homozygosity mapping. DNA samples from affected and healthy individuals from 14 Indonesian families segregating autosomal recessive, X-linked, or isolated RP were collected. Homozygosity mapping was conducted using Illumina 6k or Affymetrix 5.0 single nucleotide polymorphism (SNP) arrays. Known autosomal recessive RP (arRP) genes residing in homozygous regions and X-linked RP genes were sequenced for mutations. In ten out of the 14 families, homozygous regions were identified that contained genes known to be involved in the pathogenesis of RP. Sequence analysis of these genes revealed seven novel homozygous mutations in ATP-binding cassette, sub-family A, member 4 (ABCA4), crumbs homolog 1 (CRB1), eyes shut homolog (Drosophila) (EYS), c-mer proto-oncogene tyrosine kinase (MERTK), nuclear receptor subfamily 2, group E, member 3 (NR2E3) and phosphodiesterase 6A, cGMP-specific, rod, alpha (PDE6A), all segregating in the respective families. No mutations were identified in the X-linked genes retinitis pigmentosa GTPase regulator (RPGR) and retinitis pigmentosa 2 (X-linked recessive; RP2). Homozygosity mapping is a powerful tool to identify the genetic defects underlying RP in the Indonesian population. Compared to studies involving patients from other populations, the same genes appear to be implicated in the etiology of recessive RP in Indonesia, although all mutations that were discovered are novel and as such may be unique for this population.

  7. Molecular genetic analysis of retinitis pigmentosa in Indonesia using genome-wide homozygosity mapping

    PubMed Central

    Siemiatkowska, Anna M.; Arimadyo, Kentar; Moruz, Luminita M.; Astuti, Galuh D.N.; de Castro-Miro, Marta; Zonneveld, Marijke N.; Strom, Tim M.; de Wijs, Ilse J.; Hoefsloot, Lies H.; Faradz, Sultana M.H.; Cremers, Frans P.M.; den Hollander, Anneke I.

    2011-01-01

    Purpose Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous retinal disorder. Despite tremendous knowledge about the genes involved in RP, little is known about the genetic causes of RP in Indonesia. Here, we aim to identify the molecular genetic causes underlying RP in a small cohort of Indonesian patients, using genome-wide homozygosity mapping. Methods DNA samples from affected and healthy individuals from 14 Indonesian families segregating autosomal recessive, X-linked, or isolated RP were collected. Homozygosity mapping was conducted using Illumina 6k or Affymetrix 5.0 single nucleotide polymorphism (SNP) arrays. Known autosomal recessive RP (arRP) genes residing in homozygous regions and X-linked RP genes were sequenced for mutations. Results In ten out of the 14 families, homozygous regions were identified that contained genes known to be involved in the pathogenesis of RP. Sequence analysis of these genes revealed seven novel homozygous mutations in ATP-binding cassette, sub-family A, member 4 (ABCA4), crumbs homolog 1 (CRB1), eyes shut homolog (Drosophila) (EYS), c-mer proto-oncogene tyrosine kinase (MERTK), nuclear receptor subfamily 2, group E, member 3 (NR2E3) and phosphodiesterase 6A, cGMP-specific, rod, alpha (PDE6A), all segregating in the respective families. No mutations were identified in the X-linked genes retinitis pigmentosa GTPase regulator (RPGR) and retinitis pigmentosa 2 (X-linked recessive; RP2). Conclusions Homozygosity mapping is a powerful tool to identify the genetic defects underlying RP in the Indonesian population. Compared to studies involving patients from other populations, the same genes appear to be implicated in the etiology of recessive RP in Indonesia, although all mutations that were discovered are novel and as such may be unique for this population. PMID:22128245

  8. SPP2 Mutations Cause Autosomal Dominant Retinitis Pigmentosa

    PubMed Central

    Liu, Yuan; Chen, Xue; Xu, Qihua; Gao, Xiang; Tam, Pancy O. S.; Zhao, Kanxing; Zhang, Xiumei; Chen, Li Jia; Jia, Wenshuang; Zhao, Qingshun; Vollrath, Douglas; Pang, Chi Pui; Zhao, Chen

    2015-01-01

    Retinitis pigmentosa (RP) shows progressive loss of photoreceptors involved with heterogeneous genetic background. Here, by exome sequencing and linkage analysis on a Chinese family with autosomal dominant RP, we identified a putative pathogenic variant, p.Gly97Arg, in the gene SPP2, of which expression was detected in multiple tissues including retina. The p.Gly97Arg was absent in 800 ethnically matched chromosomes and 1400 in-house exome dataset, and was located in the first of the two highly conserved disulfide bonded loop of secreted phosphoprotein 2 (Spp-24) encoded by SPP2. Overexpression of p.Gly97Arg and another signal peptide mutation, p.Gly29Asp, caused cellular retention of both endogenous wild type and exogenous mutants in vitro, and primarily affected rod photoreceptors in zebrafish mimicking cardinal feature of RP. Taken together, our data indicate that the two mutations of SPP2 have dominant negative effects and cellular accumulation of Spp-24 might be particularly toxic to photoreceptors and/or retinal pigment epithelium. SPP2 has a new role in retinal degeneration. PMID:26459573

  9. Bifurcation analysis of a photoreceptor interaction model for Retinitis Pigmentosa

    NASA Astrophysics Data System (ADS)

    Camacho, Erika T.; Radulescu, Anca; Wirkus, Stephen

    2016-09-01

    Retinitis Pigmentosa (RP) is the term used to describe a diverse set of degenerative eye diseases affecting the photoreceptors (rods and cones) in the retina. This work builds on an existing mathematical model of RP that focused on the interaction of the rods and cones. We non-dimensionalize the model and examine the stability of the equilibria. We then numerically investigate other stable modes that are present in the system for various parameter values and relate these modes to the original problem. Our results show that stable modes exist for a wider range of parameter values than the stability of the equilibrium solutions alone, suggesting that additional approaches to preventing cone death may exist.

  10. Visual acuity loss in recessive retinitis pigmentosa and its correlation with macular lesions.

    PubMed

    Thobani, Azzrah; Fishman, Gerald A; Genead, Mohamed; Anastasakis, Anastasios

    2011-05-01

    To determine the visual acuity loss in patients with autosomal recessive retinitis pigmentosa and its relation to the presence of macular lesions. A total of 145 patients were included in the visual acuity analysis, and 139 patients were included in the analysis of their macular status. Patients with a history of parental consanguinity or an affected sister and parents unaffected with retinitis pigmentosa were considered as having an autosomal recessive mode of inheritance. Regardless of age, 68 patients (47%) had visual acuity of 20/40 or better, 109 (75%) had better than 20/200 in at least 1 eye, and 36 (25%) had an acuity of 20/200 or worse in both eyes. An evaluation of the macular status demonstrated that 55 patients (39.6%) had no macular lesion and 77 (55.4%) had an atrophic lesion (either bull's-eye or geographic). Seventy-five percent of patients with no macular lesion had a visual acuity of 20/40 or better and 34 patients (44%) with an atrophic lesion had a visual acuity better than 20/70. These data can be useful to counsel patients on the potential visual acuity impairment likely to be observed at different ages and identify the association of visual acuity loss with macular changes.

  11. Prevalence and spatial distribution of cystoid spaces in retinitis pigmentosa: investigation with spectral domain optical coherence tomography.

    PubMed

    Makiyama, Yukiko; Oishi, Akio; Otani, Atsushi; Ogino, Ken; Nakagawa, Satoko; Kurimoto, Masafumi; Yoshimura, Nagahisa

    2014-05-01

    To investigate the prevalence and spatial distribution of cystoid spaces (CS) in retinitis pigmentosa patients with spectral domain optical coherence tomography. A total of 529 eyes of 275 patients with retinitis pigmentosa were examined with spectral domain optical coherence tomography. The presence or absence of CS was judged for each eye. Retinal layer and outer retinal status where the CS existed were also investigated. Statistical analysis was performed using 1 eye per 1 patient. Cystoid spaces were present in 119 of 529 eyes (22.5%) of 74 of 275 patients (26.9%). There were no significant differences between the cases with and without CS except for central foveal thickness (P < 0.001). Cystoid spaces were noted in the inner nuclear layer in almost all eyes (98.6%), and outer nuclear layer/outer plexiform layer was also involved in many eyes (27.8%). Cystoid spaces were sometimes seen in ganglion cell layer (6.9%). Cystoid spaces were predominantly (78.9%) distributed in the relatively preserved retina where external limiting membrane was retained. The presence of epiretinal membrane or posterior vitreous adhesion was associated with the presence of CS (P < 0.001) but showed no relationship with the spatial location of CS (P = 1.000). The prevalence of CS in patients with retinitis pigmentosa was 26.9% and contrary to previous reports, most CS were present in inner nuclear layer. In addition, most CS were observed in relatively retained retina, which is compatible to the prevailing notion. Epiretinal membrane or posterior vitreous adhesion was also associated with the development of CS. The distribution of CS in inner and preserved retina may provide insight for the pathogenesis of CS in retinitis pigmentosa.

  12. Bone marrow–derived stem cells preserve cone vision in retinitis pigmentosa

    PubMed Central

    Smith, Lois E.H.

    2004-01-01

    Retinitis pigmentosa is a heritable group of blinding diseases resulting from loss of photoreceptors, primarily rods and secondarily cones, that mediate central vision. Loss of retinal vasculature is a presumed metabolic consequence of photoreceptor degeneration. A new study shows that autologous bone marrow–derived lineage-negative hematopoietic stem cells, which incorporate into the degenerating blood vessels in two murine models of retinitis pigmentosa, rd1 and rd10, prevent cone loss. The use of autologous bone marrow might avoid problems with rejection while preserving central cone vision in a wide variety of genetically disparate retinal degenerative diseases. PMID:15372096

  13. Intravitreal Dexamethasone Implant (Ozurdex) for Refractory Macular Edema Secondary to Retinitis Pigmentosa

    PubMed Central

    Örnek, Nurgül; Örnek, Kemal; Erbahçeci, İnci Elif

    2016-01-01

    Macular edema (ME) in retinitis pigmentosa (RP) often impairs central vision dramatically. A 41-year-old woman diagnosed with RP was referred to our outpatient clinic due to severe visual deterioration in both eyes. The patient was treated with topical carbonic anhydrase inhibitors, topical corticosteroids and intravitreal triamcinolone acetonide injections, but her ME recurred. Intravitreal 0.7 mg dexamethasone implant (Ozurdex, Allergan) was administered into both eyes without complications. On the fourth day after both injections, visual acuity improved and ME almost totally resolved. No recurrence was observed at follow-up six months later. PMID:28058154

  14. Zebrafish model for the genetic basis of X-linked retinitis pigmentosa.

    PubMed

    Raghupathy, Rakesh Kotapati; McCulloch, Daphne L; Akhtar, Saeed; Al-mubrad, Turki M; Shu, Xinhua

    2013-03-01

    Retinitis pigmentosa (RP) affects 1/4000 individuals in most populations, and X-linked RP (XLRP) is one of the most severe forms of human retinal degeneration. Mutations in both the retinitis pigmentosa GTPase regulator (RPGR) gene and retinitis pigmentosa 2 (RP2) gene account for almost all cases of XLRP. The functional roles of both RPGR and RP2 in the pathogenesis of XLRP are unclear. Due to the surprisingly high degree of functional conservation between human genes and their zebrafish orthologues, the zebrafish has become an important model for human retinal disorders. In this brief review, we summarize the functional characterization of XLRP-causing genes, RPGR and RP2, in zebrafish, and highlight recent studies that provide insight into the cellular functions of both genes. This will not only shed light on disease mechanisms in XLRP but will also provide a solid platform to test RP-causing mutants before proposing XLRP gene therapy trials.

  15. Optical coherence tomography in retinitis pigmentosa: reproducibility and capacity to detect macular and retinal nerve fiber layer thickness alterations.

    PubMed

    Garcia-Martin, Elena; Pinilla, Isabel; Sancho, Eva; Almarcegui, Carmen; Dolz, Isabel; Rodriguez-Mena, Diego; Fuertes, Isabel; Cuenca, Nicolas

    2012-09-01

    To evaluate the ability of time-domain and Fourier-domain optical coherence tomographies (OCTs) to detect macular and retinal nerve fiber layer atrophies in retinitis pigmentosa (RP). To test the intrasession reproducibility using three OCT instruments (Stratus, Cirrus, and Spectralis). Eighty eyes of 80 subjects (40 RP patients and 40 healthy subjects) underwent a visual field examination, together with 3 macular scans and 3 optic disk evaluations by the same experienced examiner using 3 OCT instruments. Differences between healthy and RP eyes were compared. The relationship between measurements with each OCT instrument was evaluated. Repeatability was studied by intraclass correlation coefficients and coefficients of variation. Macular and retinal nerve fiber layer atrophies were detected in RP patients for all OCT parameters. Macular and retinal nerve fiber layer thicknesses, as determined by the different OCTs, were correlated but significantly different (P < 0.05). Reproducibility was moderately high using Stratus, good using Cirrus and Spectralis, and excellent using the Tru-track technology of Spectralis. In RP eyes, measurements showed higher variability compared with healthy eyes. Differences in thickness measurements existed between OCT instruments, despite there being a high degree of correlation. Fourier-domain OCT can be considered a valid and repeatability technique to detect retinal nerve fiber layer atrophy in RP patients.

  16. Dimerization deficiency of enigmatic retinitis pigmentosa-linked rhodopsin mutants

    PubMed Central

    Ploier, Birgit; Caro, Lydia N.; Morizumi, Takefumi; Pandey, Kalpana; Pearring, Jillian N.; Goren, Michael A.; Finnemann, Silvia C.; Graumann, Johannes; Arshavsky, Vadim Y.; Dittman, Jeremy S.; Ernst, Oliver P.; Menon, Anant K.

    2016-01-01

    Retinitis pigmentosa (RP) is a blinding disease often associated with mutations in rhodopsin, a light-sensing G protein-coupled receptor and phospholipid scramblase. Most RP-associated mutations affect rhodopsin's activity or transport to disc membranes. Intriguingly, some mutations produce apparently normal rhodopsins that nevertheless cause disease. Here we show that three such enigmatic mutations—F45L, V209M and F220C—yield fully functional visual pigments that bind the 11-cis retinal chromophore, activate the G protein transducin, traffic to the light-sensitive photoreceptor compartment and scramble phospholipids. However, tests of scramblase activity show that unlike wild-type rhodopsin that functionally reconstitutes into liposomes as dimers or multimers, F45L, V209M and F220C rhodopsins behave as monomers. This result was confirmed in pull-down experiments. Our data suggest that the photoreceptor pathology associated with expression of these enigmatic RP-associated pigments arises from their unexpected inability to dimerize via transmembrane helices 1 and 5. PMID:27694816

  17. Dimerization deficiency of enigmatic retinitis pigmentosa-linked rhodopsin mutants

    NASA Astrophysics Data System (ADS)

    Ploier, Birgit; Caro, Lydia N.; Morizumi, Takefumi; Pandey, Kalpana; Pearring, Jillian N.; Goren, Michael A.; Finnemann, Silvia C.; Graumann, Johannes; Arshavsky, Vadim Y.; Dittman, Jeremy S.; Ernst, Oliver P.; Menon, Anant K.

    2016-10-01

    Retinitis pigmentosa (RP) is a blinding disease often associated with mutations in rhodopsin, a light-sensing G protein-coupled receptor and phospholipid scramblase. Most RP-associated mutations affect rhodopsin's activity or transport to disc membranes. Intriguingly, some mutations produce apparently normal rhodopsins that nevertheless cause disease. Here we show that three such enigmatic mutations--F45L, V209M and F220C--yield fully functional visual pigments that bind the 11-cis retinal chromophore, activate the G protein transducin, traffic to the light-sensitive photoreceptor compartment and scramble phospholipids. However, tests of scramblase activity show that unlike wild-type rhodopsin that functionally reconstitutes into liposomes as dimers or multimers, F45L, V209M and F220C rhodopsins behave as monomers. This result was confirmed in pull-down experiments. Our data suggest that the photoreceptor pathology associated with expression of these enigmatic RP-associated pigments arises from their unexpected inability to dimerize via transmembrane helices 1 and 5.

  18. Autosomal recessive retinitis pigmentosa E150K opsin mice exhibit photoreceptor disorganization.

    PubMed

    Zhang, Ning; Kolesnikov, Alexander V; Jastrzebska, Beata; Mustafi, Debarshi; Sawada, Osamu; Maeda, Tadao; Genoud, Christel; Engel, Andreas; Kefalov, Vladimir J; Palczewski, Krzysztof

    2013-01-01

    The pathophysiology of the E150K mutation in the rod opsin gene associated with autosomal recessive retinitis pigmentosa (arRP) has yet to be determined. We generated knock-in mice carrying a single nucleotide change in exon 2 of the rod opsin gene resulting in the E150K mutation. This novel mouse model displayed severe retinal degeneration affecting rhodopsin's stabilization of rod outer segments (ROS). Homozygous E150K (KK) mice exhibited early-onset retinal degeneration, with disorganized ROS structures, autofluorescent deposits in the subretinal space, and aberrant photoreceptor phagocytosis. Heterozygous (EK) mice displayed a delayed-onset milder retinal degeneration. Further, mutant receptors were mislocalized to the inner segments and perinuclear region. Though KK mouse rods displayed markedly decreased phototransduction, biochemical studies of the mutant rhodopsin revealed only minimally affected chromophore binding and G protein activation. Ablation of the chromophore by crossing KK mice with mice lacking the critical visual cycle protein LRAT slowed retinal degeneration, whereas blocking phototransduction by crossing KK mice with GNAT1-deficient mice slightly accelerated this process. This study highlights the importance of proper higher-order organization of rhodopsin in the native tissue and provides information about the signaling properties of this mutant rhodopsin. Additionally, these results suggest that patients heterozygous for the E150K mutation should be periodically reevaluated for delayed-onset retinal degeneration.

  19. Autosomal recessive retinitis pigmentosa E150K opsin mice exhibit photoreceptor disorganization

    PubMed Central

    Zhang, Ning; Kolesnikov, Alexander V.; Jastrzebska, Beata; Mustafi, Debarshi; Sawada, Osamu; Maeda, Tadao; Genoud, Christel; Engel, Andreas; Kefalov, Vladimir J.; Palczewski, Krzysztof

    2012-01-01

    The pathophysiology of the E150K mutation in the rod opsin gene associated with autosomal recessive retinitis pigmentosa (arRP) has yet to be determined. We generated knock-in mice carrying a single nucleotide change in exon 2 of the rod opsin gene resulting in the E150K mutation. This novel mouse model displayed severe retinal degeneration affecting rhodopsin’s stabilization of rod outer segments (ROS). Homozygous E150K (KK) mice exhibited early-onset retinal degeneration, with disorganized ROS structures, autofluorescent deposits in the subretinal space, and aberrant photoreceptor phagocytosis. Heterozygous (EK) mice displayed a delayed-onset milder retinal degeneration. Further, mutant receptors were mislocalized to the inner segments and perinuclear region. Though KK mouse rods displayed markedly decreased phototransduction, biochemical studies of the mutant rhodopsin revealed only minimally affected chromophore binding and G protein activation. Ablation of the chromophore by crossing KK mice with mice lacking the critical visual cycle protein LRAT slowed retinal degeneration, whereas blocking phototransduction by crossing KK mice with GNAT1-deficient mice slightly accelerated this process. This study highlights the importance of proper higher-order organization of rhodopsin in the native tissue and provides information about the signaling properties of this mutant rhodopsin. Additionally, these results suggest that patients heterozygous for the E150K mutation should be periodically reevaluated for delayed-onset retinal degeneration. PMID:23221340

  20. Gene Therapy for Retinitis Pigmentosa Caused by MFRP Mutations: Human Phenotype and Preliminary Proof of Concept

    PubMed Central

    Dinculescu, Astra; Estreicher, Jackie; Zenteno, Juan C.; Aleman, Tomas S.; Schwartz, Sharon B.; Huang, Wei Chieh; Roman, Alejandro J.; Sumaroka, Alexander; Li, Qiuhong; Deng, Wen-Tao; Min, Seok-Hong; Chiodo, Vince A.; Neeley, Andy; Liu, Xuan; Shu, Xinhua; Matias-Florentino, Margarita; Buentello-Volante, Beatriz; Boye, Sanford L.; Cideciyan, Artur V.

    2011-01-01

    Abstract Autosomal recessive retinitis pigmentosa (RP), a heterogeneous group of degenerations of the retina, can be due to mutations in the MFRP (membrane-type frizzled-related protein) gene. A patient with RP with MFRP mutations, one of which is novel and the first splice site mutation reported, was characterized by noninvasive retinal and visual studies. The phenotype, albeit complex, suggested that this retinal degeneration may be a candidate for gene-based therapy. Proof-of-concept studies were performed in the rd6 Mfrp mutant mouse model. The fast-acting tyrosine-capsid mutant AAV8 (Y733F) vector containing the small chicken β-actin promoter driving the wild-type mouse Mfrp gene was used. Subretinal vector delivery on postnatal day 14 prevented retinal degeneration. Treatment rescued rod and cone photoreceptors, as assessed by electroretinography and retinal histology at 2 months of age. This AAV-mediated gene delivery also resulted in robust MFRP expression predominantly in its normal location within the retinal pigment epithelium apical membrane and its microvilli. The clinical features of MFRP-RP and our preliminary data indicating a response to gene therapy in the rd6 mouse suggest that this form of RP is a potential target for gene-based therapy. PMID:22142163

  1. Gene therapy for retinitis pigmentosa caused by MFRP mutations: human phenotype and preliminary proof of concept.

    PubMed

    Dinculescu, Astra; Estreicher, Jackie; Zenteno, Juan C; Aleman, Tomas S; Schwartz, Sharon B; Huang, Wei Chieh; Roman, Alejandro J; Sumaroka, Alexander; Li, Qiuhong; Deng, Wen-Tao; Min, Seok-Hong; Chiodo, Vince A; Neeley, Andy; Liu, Xuan; Shu, Xinhua; Matias-Florentino, Margarita; Buentello-Volante, Beatriz; Boye, Sanford L; Cideciyan, Artur V; Hauswirth, William W; Jacobson, Samuel G

    2012-04-01

    Autosomal recessive retinitis pigmentosa (RP), a heterogeneous group of degenerations of the retina, can be due to mutations in the MFRP (membrane-type frizzled-related protein) gene. A patient with RP with MFRP mutations, one of which is novel and the first splice site mutation reported, was characterized by noninvasive retinal and visual studies. The phenotype, albeit complex, suggested that this retinal degeneration may be a candidate for gene-based therapy. Proof-of-concept studies were performed in the rd6 Mfrp mutant mouse model. The fast-acting tyrosine-capsid mutant AAV8 (Y733F) vector containing the small chicken β-actin promoter driving the wild-type mouse Mfrp gene was used. Subretinal vector delivery on postnatal day 14 prevented retinal degeneration. Treatment rescued rod and cone photoreceptors, as assessed by electroretinography and retinal histology at 2 months of age. This AAV-mediated gene delivery also resulted in robust MFRP expression predominantly in its normal location within the retinal pigment epithelium apical membrane and its microvilli. The clinical features of MFRP-RP and our preliminary data indicating a response to gene therapy in the rd6 mouse suggest that this form of RP is a potential target for gene-based therapy.

  2. [Molecular-physiological aspects of peptide regulation of function of the retina in retinitis pigmentosa].

    PubMed

    Khavinson, V Kh; Proniaeva, V E; Lin'kova, N S; Trofimova, S V; Umnpv, R S

    2014-01-01

    Peptide's bioregulators promotes restoration of the physiological activity of the retina in retinitis pigmentosa in older adults and in animal models. The molecular mechanism of physiological activity of peptides is connected with its ability to regulate synthesis of protein markers of differentiation of neurons and retinal pigment epithelium epigenetically.

  3. Phenotype of retinitis pigmentosa associated with the Ser50Thr mutation in the NRL gene.

    PubMed

    Bessant, David A R; Holder, Graham E; Fitzke, Frederick W; Payne, Annette M; Bhattacharya, Shomi S; Bird, Alan C

    2003-06-01

    We previously reported an Ser50Thr mutation in the NRL gene as a cause of autosomal dominant retinitis pigmentosa. To determine the characteristic features of the autosomal dominant retinitis pigmentosa phenotype associated with the NRL Ser50Thr mutation in affected individuals from 4 related families. Clinical records were available for 21 affected individuals; 7 underwent more extensive electrophysiologic and psychophysical testing. Night blindness was the first symptom to manifest, with onset between birth and age 16 years. Difficulty with peripheral vision was experienced between 20 and 37 years of age. Visual acuity was well preserved in younger individuals, but those older than 30 years frequently had substantial visual loss (6/36 or worse) associated with macular atrophy. Electrophysiologic testing revealed a nondetectable scotopic electroretinogram with relative preservation of the photopic electroretinogram and pattern electroretinography in the 3 youngest patients tested (aged 15-18 years). In older individuals, all components of the electroretinogram were nondetectable. Dark-adapted visual fields in younger individuals were greatly impaired, but their photopic fields remained relatively well preserved. Older patients had photopic fields limited to just a few degrees. Distinctive peripapillary chorioretinal atrophy seems to develop as the disorder progresses. The NRL Ser50Thr mutation is associated with selective loss of scotopic function before age 20 years. With time, however, the photopic system becomes affected, leading to loss of the photopic visual field and of visual acuity.

  4. Screening for mutations in RPGR and RP2 genes in Jordanian families with X-linked retinitis pigmentosa.

    PubMed

    Haddad, M F; Khabour, O F; Abuzaideh, K A Y; Shihadeh, W

    2016-06-03

    Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous disease causing progressive degeneration of retinal photoreceptor cells. X-linked RP (XLRP), in which photoreceptor degeneration begins in early childhood and complete blindness often occurs by the fourth decade of life, constitutes the most severe form of this disease. Two genes commonly associated with XLRP have previously been cloned: retinitis pigmentosa GTPase regulator (RPGR) and retinitis pigmentosa 2 (RP2). We sought to identify mutations in these genes in Jordanian families suffering from this disease. Five unrelated Jordanian families with confirmed XLRP were screened for such mutations using direct sequencing. Three mutations were identified in the ORF15 exon of RPGR. The silent g.ORF15+470G>A substitution and the g.ORF15+1822insA insertion in the 3ꞌ-untranslated region were found in both normal and affected male family members at comparable frequencies, and thus were considered normal variants. The third mutation, g.ORF15+588G>A, in which alanine is substituted by threonine, was found in all affected men and one unaffected man in the two families harboring this variant. Thus, this mutation may be pathogenic, but with incomplete penetrance. No RP2 mutations were found among the examined families. Mutation screening of RP patients is essential to understand the mechanism behind this disease and develop treatments. A complete family history is required to identify its inheritance pattern and provide genetic counseling for patients and their families.

  5. Photovoltaic Retinal Prosthesis for Restoring Sight to Patients Blinded by Retinal Injury or Degeneration

    DTIC Science & Technology

    2016-02-01

    and various motor prostheses [6][7][8] are constantly improving. Degenerative retinal diseases, such as retinitis pigmentosa and age related macular...AD_______________ Award Number: W81XWH-15-1-0009 TITLE: Photovoltaic Retinal Prosthesis for Restoring Sight to Patients Blinded by Retinal ...DATES COVERED 1 Feb 2015 - 31 Jan 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Photovoltaic Retinal Prosthesis for Restoring Sight to Patients

  6. Assessing Photoreceptor Structure in Retinitis Pigmentosa and Usher Syndrome

    PubMed Central

    Sun, Lynn W.; Johnson, Ryan D.; Langlo, Christopher S.; Cooper, Robert F.; Razeen, Moataz M.; Russillo, Madia C.; Dubra, Alfredo; Connor, Thomas B.; Han, Dennis P.; Pennesi, Mark E.; Kay, Christine N.; Weinberg, David V.; Stepien, Kimberly E.; Carroll, Joseph

    2016-01-01

    Purpose The purpose of this study was to examine cone photoreceptor structure in retinitis pigmentosa (RP) and Usher syndrome using confocal and nonconfocal split-detector adaptive optics scanning light ophthalmoscopy (AOSLO). Methods Nineteen subjects (11 RP, 8 Usher syndrome) underwent ophthalmic and genetic testing, spectral-domain optical coherence tomography (SD-OCT), and AOSLO imaging. Split-detector images obtained in 11 subjects (7 RP, 4 Usher syndrome) were used to assess remnant cone structure in areas of altered cone reflectivity on confocal AOSLO. Results Despite normal interdigitation zone and ellipsoid zone appearance on OCT, foveal and parafoveal cone densities derived from confocal AOSLO images were significantly lower in Usher syndrome compared with RP. This was due in large part to an increased prevalence of non-waveguiding cones in the Usher syndrome retina. Although significantly correlated to best-corrected visual acuity and foveal sensitivity, cone density can decrease by nearly 38% before visual acuity becomes abnormal. Aberrantly waveguiding cones were noted within the transition zone of all eyes and corresponded to intact inner segment structures. These remnant cones decreased in density and increased in diameter across the transition zone and disappeared with external limiting membrane collapse. Conclusions Foveal cone density can be decreased in RP and Usher syndrome before visible changes on OCT or a decline in visual function. Thus, AOSLO imaging may allow more sensitive monitoring of disease than current methods. However, confocal AOSLO is limited by dependence on cone waveguiding, whereas split-detector AOSLO offers unambiguous and quantifiable visualization of remnant cone inner segment structure. Confocal and split-detector thus offer complementary insights into retinal pathology. PMID:27145477

  7. Heterogeneity analysis in 40 X-linked retinitis pigmentosa families

    SciTech Connect

    Teague, P.W.; Aldred, M.A.; Dempster, M.; Harrison, C.; Carothers, A.D.; Hardwick, L.J.; Evans, H.J.; Wright, A.F.; Strain, L.; Brock, D.J.H. )

    1994-07-01

    Analysis of genetic heterogeneity in 40 kindreds with X-linked retinitis pigmentosa (XLRP), with 20 polymorphic markers, showed that significant heterogeneity is present (P=.001) and that 56% of kindreds are of RP3 type and that 26% are of RP2 type. The location of the RP3 locus was found to be 0.4 cM distal to OTC in the Xp21.1 region, and that of the RP2 locus was 6.5 cM proximal to DXS7 in Xp11.2-p11.3. Bayesian probabilities of linkage to RP2, RP3, or to neither locus were calculated. This showed that 20 of 40 kindreds could be assigned to one or the other locus, with a probability >.70 (14 kindreds with RP3 and 6 kindreds with RP2 disease). A further three kindreds were found to be unlinked to either locus, with a probability >.8. The remaining 17 kindreds could not be classified unambiguously. This highlights the difficulty of classifying families in the presence of genetic heterogeneity, where two loci are separated by an estimated 16 cM. 34 refs., 1 fig., 4 tabs.

  8. A novel locus for X-linked retinitis pigmentosa.

    PubMed

    Tong, Zongzhong; Yang, Zhenglin; Meyer, J Jay; McInnes, Allen W; Xue, Lai; Azimi, Asif M; Baird, Jenn; Zhao, Yu; Pearson, Erik; Wang, Changguan; Chen, Yali; Zhang, Kang

    2006-07-01

    Retinitis pigmentosa (RP) is the most prevalent group of inherited retinopathies and demonstrates considerable clinical and genetic heterogeneity, with wide variations in disease severity, progression, and gene involvement. We studied a large family with RP to determine the pattern of inheritance and to identify the disease-causing gene/locus. Ophthalmic examination was performed on 35 family members to identify affected individuals and carriers and to characterise the disease phenotype. Genetic linkage analysis was performed using short tandem repeat (STR) polymorphic markers encompassing the known loci for Xlinked RP (xlRP) including RP2, RP3, RP6, RP23, and RP24. Mutation screening was performed by direct sequencing of PCR-amplified genomic DNA of the RP2 and RPGR genes of the affected individuals. A highly penetrant, X-linked form of RP was observed in this family. Age of onset was from 5 to 8 years and visual acuity ranged from 20/25 in children to light perception in older adults. Linkage analysis and direct sequencing showed that no known loci/genes were associated with the phenotype in this kindred. A novel disease gene locus/loci is responsible for the xlRP phenotype in this family.

  9. [Electroretinography changes in carriers of X-chromosomal retinitis pigmentosa].

    PubMed

    Brischnik, E; Niemeyer, G

    1988-05-01

    Out of five families with pedigrees typical for X-linked retinitis pigmentosa (RP) the authors examined eight definite and eight possible female carriers. Subjective symptoms were mild and variable, consisting mainly of relative nyctalopia. Ophthalmoscopic examination revealed a normal fundus, or mild changes suggestive of RP, or even marked changes. Perimetry (Goldmann) revealed some narrowing of the outer isopter corresponding to a significant reduction in visual field area. In testing dark adaptation, the final rod threshold was slightly elevated in five out of 16 subjects. Ganzfeld-electroretinography using matched band filters in conditions of dark and light adaptation to selectively stimulate rod and cone signals revealed reduced b-wave amplitudes in most cases. White stimuli, applied in dark adaptation, generated ERGs with less abnormality than the selective rod and cone ERGs. Peak times of the cone b-waves were prolonged in most cases. The ERG abnormalities were more pronounced in definite carriers and in advanced age. In some cases remarkable differences were noted between the two eyes as regards fundus morphology and ERG responses. The authors conclude that the possibility of improved genetic and educational counseling in families afflicted by X-linked RP justifies the considerable diagnostic effort involved in such examinations.

  10. Mutations in phosphodiesterase 6 identified in familial cases of retinitis pigmentosa

    PubMed Central

    Ullah, Inayat; Kabir, Firoz; Gottsch, Clare Brooks S; Naeem, Muhammad Asif; Guru, Aditya A; Ayyagari, Radha; Khan, Shaheen N; Riazuddin, Sheikh; Akram, Javed; Riazuddin, S Amer

    2016-01-01

    To delineate the genetic determinants associated with retinitis pigmentosa (RP), a hereditary retinal disorder, we recruited four large families manifesting cardinal symptoms of RP. We localized these families to regions on the human genome harboring the α and β subunits of phosphodiesterase 6 and identified mutations that were absent in control chromosomes. Our data suggest that mutations in PDE6A and PDE6B are responsible for the retinal phenotype in these families. PMID:27917291

  11. Vitamin A and fish oils for retinitis pigmentosa.

    PubMed

    Rayapudi, Sobharani; Schwartz, Stephen G; Wang, Xue; Chavis, Pamela

    2013-12-19

    Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual loss that may lead to legal blindness. Symptoms may become manifest during childhood or adulthood, and include poor night vision (nyctalopia) and constriction of peripheral vision (visual field loss). This field loss is progressive and usually does not reduce central vision until late in the disease course.The worldwide prevalence of RP is one in 4000, with 100,000 patients affected in the USA. At this time, there is no proven therapy for RP. The objective of this review was to synthesize the best available evidence regarding the effectiveness and safety of vitamin A and fish oils (docosahexaenoic acid (DHA)) in preventing the progression of RP. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2013, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2013), EMBASE (January 1980 to August 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 20 August 2013. We included randomized controlled trials (RCTs) evaluating the effectiveness of vitamin A, fish oils (DHA) or both, as a treatment for RP. We excluded cluster-randomized trials and cross-over trials. We pre-specified the following outcomes: mean change from baseline visual field, mean change from baseline electroretinogram (ERG) amplitudes, and anatomic changes as measured by optical coherence tomography (OCT), at one

  12. Vitamin A and fish oils for retinitis pigmentosa

    PubMed Central

    Rayapudi, Sobharani; Schwartz, Stephen G; Wang, Xue; Chavis, Pamela

    2014-01-01

    Background Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual loss that may lead to legal blindness. Symptoms may become manifest during childhood or adulthood, and include poor night vision (nyctalopia) and constriction of peripheral vision (visual field loss). This field loss is progressive and usually does not reduce central vision until late in the disease course. The worldwide prevalence of RP is one in 4000, with 100,000 patients affected in the USA. At this time, there is no proven therapy for RP. Objectives The objective of this review was to synthesize the best available evidence regarding the effectiveness and safety of vitamin A and fish oils (docosahexaenoic acid (DHA)) in preventing the progression of RP. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2013, Issue 7),Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2013), EMBASE (January 1980 to August 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2013), the meta Register of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en).We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 20 August 2013. Selection criteria We included randomized controlled trials (RCTs) evaluating the effectiveness of vitamin A, fish oils (DHA) or both, as a treatment for RP. We excluded cluster-randomized trials and cross-over trials. Data collection and analysis We pre-specified the following outcomes: mean change from baseline visual field, mean change from baseline electroretinogram (ERG

  13. Identical mutation in a novel retinal gene causes progressive rod-cone degeneration in dogs and retinitis pigmentosa in humans.

    PubMed

    Zangerl, Barbara; Goldstein, Orly; Philp, Alisdair R; Lindauer, Sarah J P; Pearce-Kelling, Susan E; Mullins, Robert F; Graphodatsky, Alexander S; Ripoll, Daniel; Felix, Jeanette S; Stone, Edwin M; Acland, Gregory M; Aguirre, Gustavo D

    2006-11-01

    Progressive rod-cone degeneration (prcd) is a late-onset, autosomal recessive photoreceptor degeneration of dogs and a homolog for some forms of human retinitis pigmentosa (RP). Previously, the disease-relevant interval was reduced to a 106-kb region on CFA9, and a common phenotype-specific haplotype was identified in all affected dogs from several different breeds and breed varieties. Screening of a canine retinal EST library identified partial cDNAs for novel candidate genes in the disease-relevant interval. The complete cDNA of one of these, PRCD, was cloned in dog, human, and mouse. The gene codes for a 54-amino-acid (aa) protein in dog and human and a 53-aa protein in the mouse; the first 24 aa, coded for by exon 1, are highly conserved in 14 vertebrate species. A homozygous mutation (TGC --> TAC) in the second codon shows complete concordance with the disorder in 18 different dog breeds/breed varieties tested. The same homozygous mutation was identified in a human patient from Bangladesh with autosomal recessive RP. Expression studies support the predominant expression of this gene in the retina, with equal expression in the retinal pigment epithelium, photoreceptor, and ganglion cell layers. This study provides strong evidence that a mutation in the novel gene PRCD is the cause of autosomal recessive retinal degeneration in both dogs and humans.

  14. Protective effect of sulforaphane against retinal degeneration in the Pde6(rd10) mouse model of retinitis pigmentosa.

    PubMed

    Kang, Kai; Yu, Minzhong

    2017-09-22

    Retinitis pigmentosa (RP) is a group of inherited diseases characterized by the death of rod photoreceptors, followed by the death of cone photoreceptors, progressively leading to partial or complete blindness. Currently no specific treatment is available for RP patients. Sulforaphane (SFN) has been confirmed to be an effective antioxidant in the treatment of many diseases. In this study, we tested the therapeutic effects of SFN against photoreceptor degeneration in Pde6b(rd10) mice. rd10 mice and C57/BL6 wild-type (WT) mice were treated with SFN and saline, respectively, from P6 to P20. Electroretinography (ERG), terminal deoxynucleotidyl transferase dUTP nick end labeling and western blot were tested, respectively, at P21 for the analysis of retinal function, retinal cell apoptosis or death and the protein express of GRP78/BiP (TUNEL) as a marker of endoplasmic reticulum (ER) stress. Compared with the saline group, the SFN-treated group showed significantly higher ERG a-wave and b-wave amplitudes, less photoreceptor death, and the downregulation of GRP78/BiP. Our data showed that SFN ameliorated the retinal degeneration of rd10 mice, which is possibly related to the downregulation of GRP78 expression.

  15. High Symmetry of Visual Acuity and Visual Fields in RPGR-Linked Retinitis Pigmentosa.

    PubMed

    Bellingrath, Julia-Sophia; Ochakovski, G Alex; Seitz, Immanuel P; Kohl, Susanne; Zrenner, Eberhart; Hanig, Nicola; Prokisch, Holger; Weber, Bernhard H; Downes, Susan M; Ramsden, Simon; MacLaren, Robert E; Fischer, M Dominik

    2017-09-01

    Mutations in retinitis pigmentosa GTPase regulator (RPGR) cause 70% to 90% of X-linked retinitis pigmentosa (XLRP3) cases, making this gene a high-yield target for gene therapy. This study analyzed the utility of relevant clinical biomarkers to assess symmetry and rate of progression in XLRP3. A retrospective, cross-sectional analysis of 50 XLRP3 patients extracted clinical data including visual acuity (VA), visual fields (I4e and III4e targets), foveal thickness, and ERG data points alongside molecular genetic data. Symmetry was assessed by using linear regression analysis. Kaplan-Meier survival curves (KMCs) and generalized linear mixed model calculations were used to describe disease progression. Ninety-six percent of patients exhibited a rod-cone phenotype, and 4% a cone-rod phenotype. Open reading frame 15 (ORF15) was confirmed as a mutational hotspot within RPGR harboring 73% of exonic mutations. Significant variability, but no clear genotype-phenotype relationship, could be shown between mutations located in exons 1-14 versus ORF15. All biomarkers suggested a high degree of symmetry between eyes but demonstrated different estimates of disease progression. VA and foveal thickness, followed by perimetry III4e, were the most useful endpoints to evaluate progression. KMC estimates predicted a loss of 6/6 vision at a mean of 34 years (±2.9; 95% confidence interval). XLRP3 affects retinal structure and function symmetrically, supporting the use of the fellow eye as an internal control in interventional trials. VA and kinetic visual fields (III4e) seem promising functional outcome measures to assess disease progression. KMC analysis predicted the most severe decline in vision between the third and fourth decade of life.

  16. Multimodal imaging of central retinal disease progression in a 2 year mean follow up of Retinitis Pigmentosa

    PubMed Central

    Sujirakul, Tharikarn; Lin, Michael K.; Duong, Jimmy; Wei, Ying; Lopez-Pintado, Sara; Tsang, Stephen H.

    2015-01-01

    Purpose To determine the rate of progression and optimal follow up time in patients with advanced stage retinitis pigmentosa (RP) comparing the use of fundus autofluorescence imaging and spectral domain optical coherence tomography. Design Retrospective analysis of progression rate. Methods Longitudinal imaging follow up in 71 patients with retinitis pigmentosa was studied using the main outcome measurements of hyperautofluoresent ring horizontal diameter and vertical diameter along with ellipsoid zone line width from spectral domain optical coherence tomography. Test-retest reliability and the rate of progression were calculated. The interaction between the progression rates was tested for sex, age, mode of inheritance, and baseline measurement size. Symmetry of left and right eye progression rate was also tested. Results Significant progression was observed in >75% of patients during the 2 year mean follow up. The mean annual progression rates of ellipsoid zone line, and hyperautofluorescent ring horizontal diameter and vertical diameter were 0.45° (4.9%), 0.51° (4.1%), and 0.42° (4.0%), respectively. The e llipsoid zone line width, and hyperautofluorescent ring horizontal diameter and vertical diameter had low test-retest variabilities of 8.9%, 9.5% and 9.6%, respectively. This study is the first to demonstrate asymmetrical structural progression rate between right and left eye, which was found in 19% of patients. The rate of progression was significantly slower as the disease approached the fovea, supporting the theory that RP progresses in an exponential fashion. No significant interaction between progression rate and patient age, sex, or mode of inheritance was observed. Conclusions Fundus autofluorescence and optical coherence tomography detect progression in patients with RP reliably and with strong correlation. These parameters may be useful alongside functional assessments as the outcome measurements for future therapeutic trials. Follow-up at 1 year

  17. Multimodal Imaging of Central Retinal Disease Progression in a 2-Year Mean Follow-up of Retinitis Pigmentosa.

    PubMed

    Sujirakul, Tharikarn; Lin, Michael K; Duong, Jimmy; Wei, Ying; Lopez-Pintado, Sara; Tsang, Stephen H

    2015-10-01

    To determine the rate of progression and optimal follow-up time in patients with advanced-stage retinitis pigmentosa (RP) comparing the use of fundus autofluorescence imaging and spectral-domain optical coherence tomography. Retrospective analysis of progression rate. Longitudinal imaging follow-up in 71 patients with retinitis pigmentosa was studied using the main outcome measurements of hyperautofluoresent ring horizontal diameter and vertical diameter along with ellipsoid zone line width from spectral-domain optical coherence tomography. Test-retest reliability and the rate of progression were calculated. The interaction between the progression rates was tested for sex, age, mode of inheritance, and baseline measurement size. Symmetry of left and right eye progression rate was also tested. Significant progression was observed in >75% of patients during the 2-year mean follow-up. The mean annual progression rates of ellipsoid zone line and hyperautofluorescent ring horizontal diameter and vertical diameter were 0.45 degree (4.9%), 0.51 degree (4.1%), and 0.42 degree (4.0%), respectively. The ellipsoid zone line width and hyperautofluorescent ring horizontal diameter and vertical diameter had low test-retest variabilities of 8.9%, 9.5%, and 9.6%, respectively. This study is the first to demonstrate asymmetrical structural progression rate between right and left eye, which was found in 19% of patients. The rate of progression was significantly slower as the disease approached the fovea, supporting the theory that RP progresses in an exponential fashion. No significant interaction between progression rate and patient age, sex, or mode of inheritance was observed. Fundus autofluorescence and optical coherence tomography detect progression in patients with RP reliably and with strong correlation. These parameters may be useful alongside functional assessments as the outcome measurements for future therapeutic trials. Follow-up at 1-year intervals should be adequate to

  18. Four-Year Placebo-Controlled Trial of Docosahexaenoic Acid in X-Linked Retinitis Pigmentosa (DHAX Trial)

    PubMed Central

    Hoffman, Dennis R.; Hughbanks-Wheaton, Dianna K.; Pearson, N. Shirlene; Fish, Gary E.; Spencer, Rand; Takacs, Alison; Klein, Martin; Locke, Kirsten G.; Birch, David G.

    2016-01-01

    IMPORTANCE X-linked retinitis pigmentosa is a severe inherited retinal degenerative disease with a frequency of 1 in 100 000 persons. Because no cure is available for this orphan disease and treatment options are limited, slowing of disease progression would be a meaningful outcome. OBJECTIVE To determine whether high-dose docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, slows progression of X-linked retinitis pigmentosa measured by cone electroretinography (ERG). DESIGN, SETTING, AND PARTICIPANTS A 4-year, single-site, randomized, placebo-controlled, double-masked phase 2 clinical trial at a research center specializing in medical retina. Seventy-eight male patients diagnosed as having X-linked retinitis pigmentosa were randomized to DHA or placebo. Data were omitted for 2 patients with non–X-linked retinitis pigmentosa and 16 patients who were unable to follow protocol during the first year. The remaining participants were tested annually and composed a modified intent-to-treat cohort (DHA group, n = 33; placebo group, n = 27). INTERVENTIONS All participants received a multivitamin and were randomly assigned to oral DHA (30 mg/kg/d) or placebo. MAIN OUTCOMES AND MEASURES The primary outcome was the rate of loss of cone ERG function. Secondary outcomes were rod and maximal ERG amplitudes and cone ERG implicit times. Capsule counts and red blood cell DHA levels were assessed to monitor adherence. RESULTS Average (6-month to 4-year) red blood cell DHA levels were 4-fold higher in the DHA group than in the placebo group (P < .001). There was no difference between the DHA and placebo groups in the rate of cone ERG functional loss (0.028 vs 0.022 log µV/y, respectively; P = .30). No group differences were evident for change in rod ERG (P = .27), maximal ERG (P = .65), or cone implicit time (no change over 4 years). The rate of cone loss (ie, event rate) was markedly reduced compared with rates in previous studies. No severe treatment-emergent adverse

  19. Effect of Purified Murine NGF on Isolated Photoreceptors of a Rodent Developing Retinitis Pigmentosa

    PubMed Central

    Rocco, Maria Luisa; Balzamino, Bijorn Omar; Petrocchi Passeri, Pamela; Micera, Alessandra; Aloe, Luigi

    2015-01-01

    A number of different studies have shown that neurotrophins, including nerve growth factor (NGF) support the survival of retinal ganglion neurons during a variety if insults. Recently, we have reported that that eye NGF administration can protect also photoreceptor degeneration in a mice and rat with inherited retinitis pigmentosa. However, the evidence that NGF acts directly on photoreceptors and that other retinal cells mediate the NGF effect could not be excluded. In the present study we have isolated retinal cells from rats with inherited retinitis pigmentosa (RP) during the post-natal stage of photoreceptor degenerative. In presence of NGF, these cells are characterized by enhanced expression of NGF-receptors and rhodopsin, the specific marker of photoreceptor and better cell survival, as well as neuritis outgrowth. Together these observations support the hypothesis that NGF that NGF acts directly on photoreceptors survival and prevents photoreceptor degeneration as previously suggested by in vivo studies. PMID:25897972

  20. Effect of purified murine NGF on isolated photoreceptors of a rodent developing retinitis pigmentosa.

    PubMed

    Rocco, Maria Luisa; Balzamino, Bijorn Omar; Petrocchi Passeri, Pamela; Micera, Alessandra; Aloe, Luigi

    2015-01-01

    A number of different studies have shown that neurotrophins, including nerve growth factor (NGF) support the survival of retinal ganglion neurons during a variety if insults. Recently, we have reported that that eye NGF administration can protect also photoreceptor degeneration in a mice and rat with inherited retinitis pigmentosa. However, the evidence that NGF acts directly on photoreceptors and that other retinal cells mediate the NGF effect could not be excluded. In the present study we have isolated retinal cells from rats with inherited retinitis pigmentosa (RP) during the post-natal stage of photoreceptor degenerative. In presence of NGF, these cells are characterized by enhanced expression of NGF-receptors and rhodopsin, the specific marker of photoreceptor and better cell survival, as well as neuritis outgrowth. Together these observations support the hypothesis that NGF that NGF acts directly on photoreceptors survival and prevents photoreceptor degeneration as previously suggested by in vivo studies.

  1. Human iPSC derived disease model of MERTK-associated retinitis pigmentosa

    PubMed Central

    Lukovic, Dunja; Artero Castro, Ana; Delgado, Ana Belen Garcia; Bernal, María de los Angeles Martín; Luna Pelaez, Noelia; Díez Lloret, Andrea; Perez Espejo, Rocío; Kamenarova, Kunka; Fernández Sánchez, Laura; Cuenca, Nicolás; Cortón, Marta; Avila Fernandez, Almudena; Sorkio, Anni; Skottman, Heli; Ayuso, Carmen; Erceg, Slaven; Bhattacharya, Shomi S.

    2015-01-01

    Retinitis pigmentosa (RP) represents a genetically heterogeneous group of retinal dystrophies affecting mainly the rod photoreceptors and in some instances also the retinal pigment epithelium (RPE) cells of the retina. Clinical symptoms and disease progression leading to moderate to severe loss of vision are well established and despite significant progress in the identification of causative genes, the disease pathology remains unclear. Lack of this understanding has so far hindered development of effective therapies. Here we report successful generation of human induced pluripotent stem cells (iPSC) from skin fibroblasts of a patient harboring a novel Ser331Cysfs*5 mutation in the MERTK gene. The patient was diagnosed with an early onset and severe form of autosomal recessive RP (arRP). Upon differentiation of these iPSC towards RPE, patient-specific RPE cells exhibited defective phagocytosis, a characteristic phenotype of MERTK deficiency observed in human patients and animal models. Thus we have created a faithful cellular model of arRP incorporating the human genetic background which will allow us to investigate in detail the disease mechanism, explore screening of a variety of therapeutic compounds/reagents and design either combined cell and gene- based therapies or independent approaches. PMID:26263531

  2. A novel nonsense mutation in rhodopsin gene in two Indonesian families with autosomal recessive retinitis pigmentosa.

    PubMed

    Kartasasmita, Arief; Fujiki, Keiko; Iskandar, Erwin; Sovani, Iwan; Fujimaki, Takuro; Murakami, Akira

    2011-03-01

    To report a novel, identical nonsense mutation in the rhodopsin (RHO) gene in two Indonesian families with autosomal recessive retinitis pigmentosa (arRP). Mutation screening for the RHO gene was performed in 38 unrelated patients with retinitis pigmentosa (RP) by direct sequencing. Clinical features were also characterized, through complete ophthalmologic examination. Family members of RP patients testing positive for the RHO gene were subjected to genetic and clinical examination. To assess the founder effect in the two families, haplotype analysis also was performed. A novel homozygous nonsense mutation was detected in two patients by a G to A transition at nucleotide position 482 in exon 2 of the RHO gene, resulting in substitution of a tryptophan-to-stop at codon 161 (c.482G>A, p.W161X). Examination of family members of these 2 patients showed that the affected members were homozygous and unaffected carriers were heterozygous for the p.W161X mutation. Haplotype analysis revealed that members of the two families carried the same disease-associated variants in markers (IVS1 RHO and D3S2322). No p.W161X mutations were detected in 45 normal Indonesian subjects, nor were any mutations detected in exons 1-5 of the RHO gene in the remaining 36 RP patients. We detected a novel, recessive nonsense mutation (p.W161X) in the RHO gene of two families through mutation screening of RHO in 38 Indonesian RP patients. Haplotype analysis suggested that p.W161X was the founder mutation.

  3. Exome sequencing identifies RDH12 compound heterozygous mutations in a family with severe retinitis pigmentosa.

    PubMed

    Chacon-Camacho, Oscar F; Jitskii, Serguei; Buentello-Volante, Beatriz; Quevedo-Martinez, Jonathan; Zenteno, Juan C

    2013-10-10

    Retinitis pigmentosa (RP) is the most prevalent type of inherited retinal degeneration and one of the commonest causes of genetically determined visual dysfunction worldwide. To date, approximately 35 genes have been associated with nonsyndromic autosomal recessive RP (arRP), however the small contribution of each gene to the total prevalence of arRP and the lack of a clear genotype-phenotype correlation complicate the genetic analysis in affected patients. Next generation sequencing technologies are powerful and cost-effective methods for detecting causative mutations in both sporadic and familial RP cases. A Mexican family with 5 members affected from arRP was studied. All patients underwent a complete ophthalmologic examination. Molecular methods included genome-wide SNP homozygosity mapping, exome sequencing analysis, and Sanger-sequencing confirmation of causal mutations. No regions of shared homozygosity among affected subjects were identified. Exome sequencing in a single patient allowed the detection of two missense mutations in the RDH12 gene: a c.446T>C transition predicting a novel p.L149P substitution, and a c.295C>A transversion predicting a previously reported p.L99I replacement. Sanger sequencing confirmed that all affected subjects carried both RDH12 mutations. This study adds to the molecular spectrum of RDH12-related retinopathy and offers an additional example of the power of exome sequencing in the diagnosis of recessively inherited retinal degenerations. © 2013 Elsevier B.V. All rights reserved.

  4. Molecular analysis and genetic mapping of the rhodopsin gene in families with autosomal dominant retinitis pigmentosa

    SciTech Connect

    Bunge, S.; Wedemann, H.; Samanns, C.; Horn, M.; Schwinger, E.; Gal, A. ); David, D. ); Terwilliger, D.J.; Ott, J. ); Born, L.I. van den )

    1993-07-01

    Eighty-eight patients/families with autosomal dominant retinitis pigmentosa (RP) were screened for rhodopsin mutations. Direct sequencing revealed 13 different mutations in a total of 14 (i.e., 16%) unrelated patients. Five of these mutations (T4K, Q28H, R135G, F220C, and C222R) have not been reported so far. In addition, multipoint linkage analysis was performed on two large families with autosomal dominant RP due to rhodopsin mutations by using five DNA probes from 3q21-q24. No tight linkage was found between the rhodopsin locus (RHO) and D3S47 ([theta][sub max] = 0.08). By six-point analysis, RHO was localized in the region between D3S21 and D3S47, with a maximum lod score of 13.447 directly at D3S20. 13 refs., 1 fig., 2 tabs.

  5. Severe early onset retinitis pigmentosa in a Moroccan patient with Heimler syndrome due to novel homozygous mutation of PEX1 gene.

    PubMed

    Ratbi, Ilham; Jaouad, Imane Cherkaoui; Elorch, Hamza; Al-Sheqaih, Nada; Elalloussi, Mustapha; Lyahyai, Jaber; Berraho, Amina; Newman, William G; Sefiani, Abdelaziz

    2016-10-01

    Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation. It is the mildest form known to date of peroxisome biogenesis disorder caused by hypomorphic mutations of PEX1 and PEX6 genes. We report on a second Moroccan family with Heimler syndrome with early onset, severe visual impairment and important phenotypic overlap with Usher syndrome. The patient carried a novel homozygous missense variant c.3140T > C (p.Leu1047Pro) of PEX1 gene. As standard biochemical screening of blood for evidence of a peroxisomal disorder did not provide a diagnosis in the individuals with HS, patients with SNHL and retinal pigmentation should have mutation analysis of PEX1 and PEX6 genes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. In Vivo CRISPR/Cas9 Gene Editing Corrects Retinal Dystrophy in the S334ter-3 Rat Model of Autosomal Dominant Retinitis Pigmentosa.

    PubMed

    Bakondi, Benjamin; Lv, Wenjian; Lu, Bin; Jones, Melissa K; Tsai, Yuchun; Kim, Kevin J; Levy, Rachelle; Akhtar, Aslam Abbasi; Breunig, Joshua J; Svendsen, Clive N; Wang, Shaomei

    2016-03-01

    Reliable genome editing via Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 may provide a means to correct inherited diseases in patients. As proof of principle, we show that CRISPR/Cas9 can be used in vivo to selectively ablate the rhodopsin gene carrying the dominant S334ter mutation (Rho(S334)) in rats that model severe autosomal dominant retinitis pigmentosa. A single subretinal injection of guide RNA/Cas9 plasmid in combination with electroporation generated allele-specific disruption of Rho(S334), which prevented retinal degeneration and improved visual function.

  7. In Vivo CRISPR/Cas9 Gene Editing Corrects Retinal Dystrophy in the S334ter-3 Rat Model of Autosomal Dominant Retinitis Pigmentosa

    PubMed Central

    Bakondi, Benjamin; Lv, Wenjian; Lu, Bin; Jones, Melissa K; Tsai, Yuchun; Kim, Kevin J; Levy, Rachelle; Akhtar, Aslam Abbasi; Breunig, Joshua J; Svendsen, Clive N; Wang, Shaomei

    2016-01-01

    Reliable genome editing via Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 may provide a means to correct inherited diseases in patients. As proof of principle, we show that CRISPR/Cas9 can be used in vivo to selectively ablate the rhodopsin gene carrying the dominant S334ter mutation (RhoS334) in rats that model severe autosomal dominant retinitis pigmentosa. A single subretinal injection of guide RNA/Cas9 plasmid in combination with electroporation generated allele-specific disruption of RhoS334, which prevented retinal degeneration and improved visual function. PMID:26666451

  8. Flavonoid allosteric modulation of mutated visual rhodopsin associated with retinitis pigmentosa.

    PubMed

    Herrera-Hernández, María Guadalupe; Ramon, Eva; Lupala, Cecylia S; Tena-Campos, Mercè; Pérez, Juan J; Garriga, Pere

    2017-09-11

    Dietary flavonoids exhibit many biologically-relevant functions and can potentially have beneficial effects in the treatment of pathological conditions. In spite of its well known antioxidant properties, scarce structural information is available on the interaction of flavonoids with membrane receptors. Advances in the structural biology of a specific class of membrane receptors, the G protein-coupled receptors, have significantly increased our understanding of drug action and paved the way for developing improved therapeutic approaches. We have analyzed the effect of the flavonoid quercetin on the conformation, stability and function of the G protein-coupled receptor rhodopsin, and the G90V mutant associated with the retinal degenerative disease retinitis pigmentosa. By using a combination of experimental and computational methods, we suggest that quercetin can act as an allosteric modulator of opsin regenerated with 9-cis-retinal and more importantly, that this binding has a positive effect on the stability and conformational properties of the G90V mutant associated with retinitis pigmentosa. These results open new possibilities to use quercetin and other flavonoids, in combination with specific retinoids like 9-cis-retinal, for the treatment of retinal degeneration associated with retinitis pigmentosa. Moreover, the use of flavonoids as allosteric modulators may also be applicable to other members of the G protein-coupled receptors superfamily.

  9. Mutations P51U and G122E in retinal transcription factor NRL associated with autosomal dominant and sporadic retinitis pigmentosa.

    PubMed

    Martinez-Gimeno, M; Maseras, M; Baiget, M; Beneito, M; Antiñolo, G; Ayuso, C; Carballo, M

    2001-06-01

    Retinitis pigmentosa (RP) is the most frequent form of inherited retinopathy. RP is genetically heterogeneous with autosomal dominant, autosomal recessive and X-linked forms. Autosomal dominant retinitis pigmentosa (adRP) accounts for about 20-25% of all RP cases. At least ten adRP loci have so far been mapped. However, mutations causing adRP have been identified only in four retina-specific genes: RHO (encoding rhodopsin) in approximately 20% of adRP families, peripherin/RDS (3-5% of adRP) and recently RP1 (Pierce et al., 1999, Sulivan et al., 1999) and NRL gene. Only one mutation in the NRL gene causing adRP has so far been reported (Bessant et al., 1999). Here we report a novel mutation Pro51Leu in an adRP Spanish family supporting that mutation in NRL is the cause of adRP. A second missense mutation Gly122Glu has been observed in a simplex RP patient that may represent a sporadic case of retinitis pigmentosa. Hum Mutat 17:520, 2001. Copyright 2001 Wiley-Liss, Inc.

  10. A profile of transcriptomic changes in the rd10 mouse model of retinitis pigmentosa

    PubMed Central

    Uren, Philip J.; Lee, Justine T.; Doroudchi, M. Mehdi; Smith, Andrew D.

    2014-01-01

    Purpose Retinitis pigmentosa (RP) is a photoreceptor disease that affects approximately 100,000 people in the United States. Treatment options are limited, and the prognosis for most patients is progressive vision loss. Unfortunately, understanding of the molecular underpinnings of RP initiation and progression is still limited. However, the development of animal models of RP, coupled with high-throughput sequencing, has provided an opportunity to study the underlying cellular and molecular changes in this disease. Methods Using RNA-Seq, we present the first retinal transcriptome analysis of the rd10 murine model of retinal degeneration. Results Our data confirm the loss of rod-specific transcripts and the increased relative expression of Müller-specific transcripts, emphasizing the important role of reactive gliosis and innate immune activation in RP. Moreover, we report substantial changes in relative isoform usage among neuronal differentiation and morphogenesis genes, including a marked shift to shorter transcripts. Conclusions Our analyses implicate remodeling of the inner retina and possible Müller cell dedifferentiation. PMID:25489233

  11. Localization of a new autosomal dominant retinitis pigmentosa gene on chromosome 17p screeningof candidate genes

    SciTech Connect

    Greenberg, J.; Goliath, R.; Shugart, Y.Y.

    1994-09-01

    A new gene locus for autosomal dominant retinitis pigmentosa (ADRP) on 17p has been identified in a large South African (SA) family consisting of 28 living affected individuals in 4 successive generations. This is the first ADRP gene to be reported from SA. The human recoverin (RCVN) gene, which codes for a retinal-specific protein important in recovery to the dark state after visual excitation, has been mapped to 17p13.1 and was considered as a prime candidate gene for the disorder in this family. Mutation screening (using 8 different electrophoretic conditions to resolve heteroduplexes and SSCPs) did not produce any evidence of RCVN being involved in the pathogenesis of ADRP in this SA family. In addition, a mobility shift detected within exon 1 of the RCVN gene did not track with the ADRP phenotype. RP patients from 77 SA families and 30 normal individuals are being examined to establish the frequency of this polymorphism in the SA population. Highly polymorphic markers from 17p13 are now being sought in order to establish the minimum region containing this novel ADRP-SA gene. Two additional recently described retinal-expressed cDNAs, guanylyl cyclase and pigment epithelium-derived factor, which map to 17p13.1, will be tested for tight linkage to ADRP-SA.

  12. Missense mutation (E150K) of rhodopsin in autosomal recessive retinitis pigmentosa

    SciTech Connect

    Orth, U.; Oehlmann, R.; Gal, A.

    1994-09-01

    Missense or nonsense mutations of the rhodopsin gene have been implied in the pathogenesis of at least 3 different traits; autosomal dominant retinitis pigmentosa (adRP), congenital stationary night blindness (CSNB), and autosomal recessive retinitis pigmentosa (arRP). For the latter, a single patient has been reported with a nonsense mutation at codon 249 on both alleles. Heterozygous carriers of missense mutations of rhodopsin develop either adRP or CSNB depending on the particular amino acid substitution. Four of the 9 siblings from a consanguineous marriage in southern India were reported the have arRP. Mutational screening and sequencing of the rhodopsin gene revealed a G-to-A transition of the first nucleotide at codon 150 in exon II, which alters glutamate to lysine. The E150K mutation was present in the 4 patients in homozygous form, whereas the parents and 2 of the siblings were heterozygotes. Two-point analysis produced a Zmax=3.46 at theta=0.00. Two unaffected siblings who are heterozygotes for the E150K mutation underwent a thorough ophthalmological and psychophysical examination. No clinical abnormalities were found although these individuals were over forty, whereas the onset of RP in their affected siblings was in the second decade. Collectively, both the genetic and clinical findings strongly suggest that the E150K mutation of rhodopsin is recessive in this family. Glu150 forms part of the CD cytoplasmic loop of rhodopsin, which has been implicated in the binding and activation of transducin. We speculate that E150K leads to RP because the mutant protein may be incapable of activating transducin. It is tempting to speculate that, in addition to mutations in the genes for rhodopsin and the {beta}-subunit of PDE, mutations in the genes for transducin may also result in arRP.

  13. The Self-Concept of Spanish Young Adults with Retinitis Pigmentosa

    ERIC Educational Resources Information Center

    Lopez-Justicia, Maria Dolores; Cordoba, Inmaculada Nieto

    2006-01-01

    Retinitis pigmentosa (RP) is a degenerative disease of the retina that causes the severe impairment of visual functioning similar to low vision, leading, in many cases, to blindness. Because the construct of self-concept plays a key role in personality, this study was designed to measure self-concept in a group of young adults with RP. The…

  14. Connecting Research on Retinitis Pigmentosa to the Practice of Orientation and Mobility.

    ERIC Educational Resources Information Center

    Geruschat, Duane R.; Turano, Kathleen A.

    2002-01-01

    Retinitis pigmentosa (RP) causes restriction of the visual field, progressive vision loss, and night blindness. This article presents an overview of the most common problems in orientation and mobility (O&M) for individuals with RP, appropriate interventions, vision science discoveries related to RP, and the impact of RP on functional visual…

  15. Subjective Perception of Visual Distortions or Scotomas in Individuals with Retinitis Pigmentosa

    ERIC Educational Resources Information Center

    Wittich, Walter; Watanabe, Donald H.; Kapusta, Michael A.; Overbury, Olga

    2011-01-01

    It is often assumed that persons who develop ocular disease have some form of visual experience that makes them aware of their deficits. However, in the case of peripheral field loss or decreasing vision in dim lighting, as in retinitis pigmentosa, for example, symptoms are more obscure and may not be as easily identified by the persons who have…

  16. Subjective Perception of Visual Distortions or Scotomas in Individuals with Retinitis Pigmentosa

    ERIC Educational Resources Information Center

    Wittich, Walter; Watanabe, Donald H.; Kapusta, Michael A.; Overbury, Olga

    2011-01-01

    It is often assumed that persons who develop ocular disease have some form of visual experience that makes them aware of their deficits. However, in the case of peripheral field loss or decreasing vision in dim lighting, as in retinitis pigmentosa, for example, symptoms are more obscure and may not be as easily identified by the persons who have…

  17. Connecting Research on Retinitis Pigmentosa to the Practice of Orientation and Mobility.

    ERIC Educational Resources Information Center

    Geruschat, Duane R.; Turano, Kathleen A.

    2002-01-01

    Retinitis pigmentosa (RP) causes restriction of the visual field, progressive vision loss, and night blindness. This article presents an overview of the most common problems in orientation and mobility (O&M) for individuals with RP, appropriate interventions, vision science discoveries related to RP, and the impact of RP on functional visual…

  18. Vision Test Variability in Retinitis Pigmentosa and Psychosocial Factors

    PubMed Central

    Bittner, Ava K.; Ibrahim, Mohamed A.; Haythornthwaite, Jennifer A.; Diener-West, Marie; Dagnelie, Gislin

    2011-01-01

    Purpose We explored whether greater amounts of short-term variability in visual acuity (VA), contrast sensitivity (CS), or visual field (VF) in retinitis pigmentosa (RP) was related to disease severity or psychosocial factors. Methods We obtained spectral domain-optical coherence tomography in 27 RP subjects and determined variability (SD) of VA, CS and VF during a mean of 16 tests self-administered at home on a personal computer (PC) twice a week. Subjects completed the Positive and Negative Affect Schedules at each PC-test session, and SF-36 general health and Beck Depression Inventory questionnaires on one occasion. Results There was a 0.10 log unit increase in VA variability for every 0.58 logMAR increase (worse mean VA) (p=0.001). For subjects with reduced foveal thickness, mean VA explained more of the total VA variability than foveal thickness (R2=0.72 and 0.46, respectively, in simple linear regressions). There was a statistically significant 4.3% increased log VF area variability for every 50% mean log VF area decrease (p<0.001); explaining most of the total variability in log VF area variability (R2=0.44). When controlling for mean log VF area, there was a statistically significant increase in log VF area variability for subjects with greater than minimal depressive symptoms (p=0.015), with increased mean irritability scores (p=0.02), decreased SF-36 physical functioning subscale scores (p=0.03), or decreased mean score for feeling active, strong and proud (p=0.008) (adjusted R2=0.62). CS variability was low, and not statistically significantly related to mean CS, macular thickness or psychosocial factors. Conclusions Increased VA and VF variability was predicted largely by increased RP severity. Greater VF variability occurred in subjects with reduced VF who reported less physical activity or increased negative psychosocial states. These associations should be considered during clinical exams and trials for RP. PMID:21946786

  19. Visual Function in Carriers of X-Linked Retinitis Pigmentosa.

    PubMed

    Comander, Jason; Weigel-DiFranco, Carol; Sandberg, Michael A; Berson, Eliot L

    2015-09-01

    To determine the frequency and severity of visual function loss in female carriers of X-linked retinitis pigmentosa (XLRP). Case series. Two hundred seventy-six XLRP carriers with cross-sectional data (n = 242) and longitudinal data (n = 34; median follow-up, 16 years; follow-up range, 3-37 years). Half of the carriers were from RPGR- or RP2-genotyped families. Retrospective medical records review. Visual acuities, visual field areas, final dark adaptation thresholds, and full-field electroretinography (ERG) responses to 0.5-Hz and 30-Hz flashes. In genotyped families, 40% of carriers showed a baseline abnormality on at least 1 of 3 psychophysical tests. There was a wide range of function among carriers. For example, 3 of 121 (2%) genotyped carriers were legally blind because of poor visual acuity, some as young as 35 years. Visual fields were less affected than visual acuity. In all carriers, the average ERG amplitude to 30-Hz flashes was approximately 50% of normal, and the average exponential rate of amplitude loss over time was half that of XLRP males (3.7%/year vs. 7.4%/year, respectively). Among obligate carriers with affected fathers, sons, or both, 53 of 55 (96%) had abnormal baseline ERG results. Some carriers who initially had completely normal fundi in both eyes went on to experience moderately decreased vision, although not legal blindness. Among carriers with RPGR mutations, those with mutations in ORF15, compared with those in exons 1-14, had worse final dark adaptation thresholds and lower 0.5-Hz and 30-Hz ERG amplitudes. Most carriers of XLRP had mildly or moderately reduced visual function but rarely became legally blind. In most cases, obligate carriers could be identified by ERG testing. Carriers of RPGR ORF15 mutations tended to have worse visual function than carriers of RPGR exon 1 through 14 mutations. Because XLRP carrier ERG amplitudes and decay rates over time were on average half of those of affected men, these observations were

  20. AAV Mediated GDNF Secretion From Retinal Glia Slows Down Retinal Degeneration in a Rat Model of Retinitis Pigmentosa

    PubMed Central

    Dalkara, Deniz; Kolstad, Kathleen D; Guerin, Karen I; Hoffmann, Natalie V; Visel, Meike; Klimczak, Ryan R; Schaffer, David V; Flannery, John G

    2011-01-01

    Mutations in over 80 identified genes can induce apoptosis in photoreceptors, resulting in blindness with a prevalence of 1 in 3,000 individuals. This broad genetic heterogeneity of disease impacting a wide range of photoreceptor functions renders the design of gene-specific therapies for photoreceptor degeneration impractical and necessitates the development of mutation-independent treatments to slow photoreceptor cell death. One promising strategy for photoreceptor neuroprotection is neurotrophin secretion from Müller cells, the primary retinal glia. Müller glia are excellent targets for secreting neurotrophins as they span the entire tissue, ensheath all neuronal populations, are numerous, and persist through retinal degeneration. We previously engineered an adeno-associated virus (AAV) variant (ShH10) capable of efficient and selective glial cell transduction through intravitreal injection. ShH10-mediated glial-derived neurotrophic factor (GDNF) secretion from glia, generates high GDNF levels in treated retinas, leading to sustained functional rescue for over 5 months. This GDNF secretion from glia following intravitreal vector administration is a safe and effective means to slow the progression of retinal degeneration in a rat model of retinitis pigmentosa (RP) and shows significant promise as a gene therapy to treat human retinal degenerations. These findings also demonstrate for the first time that glia-mediated secretion of neurotrophins is a promising treatment that may be applicable to other neurodegenerative conditions. PMID:21522134

  1. Three families displaying the combination of Stargardt's disease with cone-rod dystrophy or retinitis pigmentosa.

    PubMed

    Klevering, B Jeroen; Maugeri, Alessandra; Wagner, Anja; Go, Sioe Lie; Vink, Carolien; Cremers, Frans P M; Hoyng, Carel B

    2004-03-01

    To investigate the clinical spectrum and molecular causes of retinal dystrophies in 3 families. Family molecular genetics study. Sixteen patients and 15 relatives in 3 families. Members of 3 families with multiple ABCA4-associated retinal disorders were clinically evaluated. Deoxyribonucleic acid samples of all affected individuals and their family members were analyzed for variants in all 50 exons of the ABCA4 gene. ABCA4-associated retinal phenotypes and mutations in the ABCA4 gene. In family A, 2 sisters were diagnosed with Stargardt's disease (STGD); the eldest sister was compound heterozygous for the mild 2588G-->C and the severe 768G-->T mutation. Another patient in this family with a severe type of retinitis pigmentosa (RP) carried the 768G-->T mutation homozygously. In family B, 2 siblings presented with an RP of severity similar to that encountered in family A. Both were homozygous for the severe IVS33+1G-->A mutation. Two other family members with STGD were compound heterozygous for the 2588G-->C and IVS33+1G-->A mutations. In family C, all 5 siblings of generation II demonstrated age-related macular degeneration (AMD). In generations III and IV, 2 STGD patients and 1 cone-rod dystrophy (CRD) patient were present. In 1 STGD patient we identified a heterozygous 768G-->T mutation. Sequence analysis of the entire ABCA4 gene did not reveal the remaining 2 mutations. Nevertheless, the 2 patients with STGD, the patient with CRD, and 2 of the AMD patients shared a common haplotype spanning the ABCA4 gene. Different mutations in the ABCA4 gene are the cause of STGD and RP or CRD in at least 2 and, possibly, 3 families. Patients with RP caused by ABCA4 mutations are characterized by an early onset and rapid progression of their retinal dystrophy, with extensive chorioretinal atrophy resulting in a very low visual acuity. Various combinations of relatively rare retinal disorders such as STGD, CRD, and RP in one family may not be as uncommon as once believed, in

  2. INTERACTION AND LOCALIZATION OF THE RETINITIS PIGMENTOSA PROTEIN RP2 AND NSF IN RETINAL PHOTORECEPTOR CELLS†

    PubMed Central

    Holopainen, Juha M.; Cheng, Christiana L.; Molday, Laurie L.; Johal, Gurp; Coleman, Jonathan; Dyka, Frank; Hii, Theresa; Ahn, Jinhi; Molday, Robert S.

    2010-01-01

    RP2 is a ubiquitously expressed protein encoded by a gene associated with X-linked retinitis pigmentosa (XLRP), a retinal degenerative disease that causes severe vision loss. Previous in vitro studies have shown that RP2 binds to ADP ribosylation factor-like 3 (Arl3) and activates its intrinsic GTPase activity, but the function of RP2 in the retina, and in particular photoreceptor cells, remains unclear. To begin to define the role of RP2 in the retina and XLRP, we have carried out biochemical studies to identify proteins in retinal cell extracts that interact with RP2. Here, we show that RP2 interacts with N-ethylmaleimide sensitive factor (NSF) in retinal cells as well as cultured embryonic kidney (HEK293) cells by mass spectrometry-based proteomics and biochemical analysis. This interaction is mediated by the N-terminal domain of NSF. The E138G and ΔI137 mutations of RP2 known to cause XLRP abolished the interaction of RP2 with the N-terminal domain of NSF. Immunofluorescence labeling studies further showed that RP2 co-localized with NSF in photoreceptors and other cells of the retina. Intense punctate staining of RP2 was observed close to the junction between the inner and outer segments beneath the connecting cilium, as well as within the synaptic region of rod and cone photoreceptors. Our studies indicate that RP2, in addition to serving as a regulator of Arl3, interacts with NSF and this complex may play an important role in membrane protein trafficking in photoreceptors and other cells of the retina. PMID:20669900

  3. NGS-based Molecular diagnosis of 105 eyeGENE(®) probands with Retinitis Pigmentosa.

    PubMed

    Ge, Zhongqi; Bowles, Kristen; Goetz, Kerry; Scholl, Hendrik P N; Wang, Feng; Wang, Xinjing; Xu, Shan; Wang, Keqing; Wang, Hui; Chen, Rui

    2015-12-15

    The National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE(®)) was established in an effort to facilitate basic and clinical research of human inherited eye disease. In order to provide high quality genetic testing to eyeGENE(®)'s enrolled patients which potentially aids clinical diagnosis and disease treatment, we carried out a pilot study and performed Next-generation sequencing (NGS) based molecular diagnosis for 105 Retinitis Pigmentosa (RP) patients randomly selected from the network. A custom capture panel was designed, which incorporated 195 known retinal disease genes, including 61 known RP genes. As a result, disease-causing mutations were identified in 52 out of 105 probands (solving rate of 49.5%). A total of 82 mutations were identified, and 48 of them were novel. Interestingly, for three probands the molecular diagnosis was inconsistent with the initial clinical diagnosis, while for five probands the molecular information suggested a different inheritance model other than that assigned by the physician. In conclusion, our study demonstrated that NGS target sequencing is efficient and sufficiently precise for molecular diagnosis of a highly heterogeneous patient cohort from eyeGENE(®).

  4. Missense mutations in the WD40 domain of AHI1 cause non-syndromic retinitis pigmentosa.

    PubMed

    Nguyen, Thanh-Minh T; Hull, Sarah; Roepman, Ronald; van den Born, L Ingeborgh; Oud, Machteld M; de Vrieze, Erik; Hetterschijt, Lisette; Letteboer, Stef J F; van Beersum, Sylvia E C; Blokland, Ellen A; Yntema, Helger G; Cremers, Frans P M; van der Zwaag, Paul A; Arno, Gavin; van Wijk, Erwin; Webster, Andrew R; Haer-Wigman, Lonneke

    2017-09-01

    Recent findings suggesting that Abelson helper integration site 1 (AHI1) is involved in non-syndromic retinal disease have been debated, as the functional significance of identified missense variants was uncertain. We assessed whether AHI1 variants cause non-syndromic retinitis pigmentosa (RP). Exome sequencing was performed in three probands with RP. The effects of the identified missense variants in AHI1 were predicted by three-dimensional structure homology modelling. Ciliary parameters were evaluated in patient's fibroblasts, and recombinant mutant proteins were expressed in ciliated retinal pigmented epithelium cells. In the three patients with RP, three sets of compound heterozygous variants were detected in AHI1 (c.2174G>A; p.Trp725* and c.2258A>T; p.Asp753Val, c.660delC; p.Ser221Glnfs*10 and c.2090C>T; p.Pro697Leu, c.2087A>G; p.His696Arg and c.2429C>T; p.Pro810Leu). All four missense variants were present in the conserved WD40 domain of Jouberin, the ciliary protein encoded by AHI1, with variable predicted implications for the domain structure. No significant changes in the percentage of ciliated cells, nor in cilium length or intraflagellar transport were detected. However, expression of mutant recombinant Jouberin in ciliated cells showed a significantly decreased enrichment at the ciliary base. This report confirms that mutations in AHI1 can underlie autosomal recessive RP. Moreover, it structurally and functionally validates the effect of the RP-associated AHI1 variants on protein function, thus proposing a new genotype-phenotype correlation for AHI1 mutation associated retinal ciliopathies. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Homozygosity mapping in autosomal recessive retinitis pigmentosa families detects novel mutations

    PubMed Central

    Marzouka, Nour al Dain; Hebrard, Maxime; Manes, Gaël; Sénéchal, Audrey; Meunier, Isabelle; Hamel, Christian P.

    2013-01-01

    Purpose Autosomal recessive retinitis pigmentosa (arRP) is a genetically heterogeneous disease resulting in progressive loss of photoreceptors that leads to blindness. To date, 36 genes are known to cause arRP, rendering the molecular diagnosis a challenge. The aim of this study was to use homozygosity mapping to identify the causative mutation in a series of inbred families with arRP. Methods arRP patients underwent standard ophthalmic examination, Goldman perimetry, fundus examination, retinal OCT, autofluorescence measurement, and full-field electroretinogram. Fifteen consanguineous families with arRP excluded for USH2A and EYS were genotyped on 250 K SNP arrays. Homozygous regions were listed, and known genes within these regions were PCR sequenced. Familial segregation and mutation analyzes were performed. Results We found ten mutations, seven of which were novel mutations in eight known genes, including RP1, IMPG2, NR2E3, PDE6A, PDE6B, RLBP1, CNGB1, and C2ORF71, in ten out of 15 families. The patients carrying RP1, C2ORF71, and IMPG2 mutations presented with severe RP, while those with PDE6A, PDE6B, and CNGB1 mutations were less severely affected. The five families without mutations in known genes could be a source of identification of novel genes. Conclusions Homozygosity mapping combined with systematic screening of known genes results in a positive molecular diagnosis in 66.7% of families. PMID:24339724

  6. Interpretation of Flood-Illuminated Adaptive Optics Images in Subjects with Retinitis Pigmentosa.

    PubMed

    Gale, Michael J; Feng, Shu; Titus, Hope E; Smith, Travis B; Pennesi, Mark E

    2016-01-01

    The purpose of this study was to correlate features on flood-illuminated adaptive optics (AO) images with color fundus, fundus autofluorescence (FAF) and spectral domain optical coherence tomography (SD-OCT) images in patients with retinitis pigmentosa (RP). We imaged 39 subjects diagnosed with RP using the rtx1™ flood-illuminated AO camera from Imagine Eyes (Orsay, France). We observed a correlation between hyper-autofluoresence changes on FAF, disruption of the interdigitation zone (IZ) on SD-OCT and loss of reflective cone profiles on AO. Four main patterns of cone-reflectivity were seen on AO: presumed healthy cone mosaics, hypo-reflective blurred cone-like structures, higher frequency disorganized hyper-reflective spots, and lower frequency hypo-reflective spots. These regions were correlated to progressive phases of cone photoreceptor degeneration observed using SD-OCT and FAF. These results help provide interpretation of en face images obtained by flood-illuminated AO in subjects with RP. However, significant ambiguity remains as to what truly constitutes a cone, especially in areas of degeneration. With further refinements in technology, flood illuminated AO imaging has the potential to provide rapid, standardized, longitudinal and lower cost imaging in patients with retinal degeneration.

  7. A Large Animal Model for CNGB1 Autosomal Recessive Retinitis Pigmentosa

    PubMed Central

    Winkler, Paige A.; Ekenstedt, Kari J.; Occelli, Laurence M.; Frattaroli, Anton V.; Bartoe, Joshua T.; Venta, Patrick J.; Petersen-Jones, Simon M.

    2013-01-01

    Retinal dystrophies in dogs are invaluable models of human disease. Progressive retinal atrophy (PRA) is the canine equivalent of retinitis pigmentosa (RP). Similar to RP, PRA is a genetically heterogenous condition. We investigated PRA in the Papillon breed of dog using homozygosity mapping and haplotype construction of single nucleotide polymorphisms within a small family group to identify potential positional candidate genes. Based on the phenotypic similarities between the PRA-affected Papillons, mouse models and human patients, CNGB1 was selected as the most promising positional candidate gene. CNGB1 was sequenced and a complex mutation consisting of the combination of a one basepair deletion and a 6 basepair insertion was identified in exon 26 (c.2387delA;2389_2390insAGCTAC) leading to a frameshift and premature stop codon. Immunohistochemistry (IHC) of pre-degenerate retinal sections from a young affected dog showed absence of labeling using a C-terminal CNGB1 antibody. Whereas an antibody directed against the N-terminus of the protein, which also recognizes the glutamic acid rich proteins arising from alternative splicing of the CNGB1 transcript (upstream of the premature stop codon), labeled rod outer segments. CNGB1 combines with CNGA1 to form the rod cyclic nucleotide gated channel and previous studies have shown the requirement of CNGB1 for normal targeting of CNGA1 to the rod outer segment. In keeping with these previous observations, IHC showed a lack of detectable CNGA1 protein in the rod outer segments of the affected dog. A population study did not identify the CNGB1 mutation in PRA-affected dogs in other breeds and documented that the CNGB1 mutation accounts for ∼70% of cases of Papillon PRA in our PRA-affected canine DNA bank. CNGB1 mutations are one cause of autosomal recessive RP making the CNGB1 mutant dog a valuable large animal model of the condition. PMID:23977260

  8. A large animal model for CNGB1 autosomal recessive retinitis pigmentosa.

    PubMed

    Winkler, Paige A; Ekenstedt, Kari J; Occelli, Laurence M; Frattaroli, Anton V; Bartoe, Joshua T; Venta, Patrick J; Petersen-Jones, Simon M

    2013-01-01

    Retinal dystrophies in dogs are invaluable models of human disease. Progressive retinal atrophy (PRA) is the canine equivalent of retinitis pigmentosa (RP). Similar to RP, PRA is a genetically heterogenous condition. We investigated PRA in the Papillon breed of dog using homozygosity mapping and haplotype construction of single nucleotide polymorphisms within a small family group to identify potential positional candidate genes. Based on the phenotypic similarities between the PRA-affected Papillons, mouse models and human patients, CNGB1 was selected as the most promising positional candidate gene. CNGB1 was sequenced and a complex mutation consisting of the combination of a one basepair deletion and a 6 basepair insertion was identified in exon 26 (c.2387delA;2389_2390insAGCTAC) leading to a frameshift and premature stop codon. Immunohistochemistry (IHC) of pre-degenerate retinal sections from a young affected dog showed absence of labeling using a C-terminal CNGB1 antibody. Whereas an antibody directed against the N-terminus of the protein, which also recognizes the glutamic acid rich proteins arising from alternative splicing of the CNGB1 transcript (upstream of the premature stop codon), labeled rod outer segments. CNGB1 combines with CNGA1 to form the rod cyclic nucleotide gated channel and previous studies have shown the requirement of CNGB1 for normal targeting of CNGA1 to the rod outer segment. In keeping with these previous observations, IHC showed a lack of detectable CNGA1 protein in the rod outer segments of the affected dog. A population study did not identify the CNGB1 mutation in PRA-affected dogs in other breeds and documented that the CNGB1 mutation accounts for ~70% of cases of Papillon PRA in our PRA-affected canine DNA bank. CNGB1 mutations are one cause of autosomal recessive RP making the CNGB1 mutant dog a valuable large animal model of the condition.

  9. Disease expression of RP1 mutations causing autosomal dominant retinitis pigmentosa.

    PubMed

    Jacobson, S G; Cideciyan, A V; Iannaccone, A; Weleber, R G; Fishman, G A; Maguire, A M; Affatigato, L M; Bennett, J; Pierce, E A; Danciger, M; Farber, D B; Stone, E M

    2000-06-01

    To determine the disease expression in heterozygotes for mutations in the RP1 gene, a newly identified cause of autosomal dominant retinitis pigmentosa (adRP). Screening strategies were used to detect disease-causing mutations in the RP1 gene, and detailed studies of phenotype were performed in a subset of the detected RP1 heterozygotes using electroretinography (ERG), psychophysics, and optical coherence tomography (OCT). Seventeen adRP families had heterozygous RP1 changes. Thirteen families had the Arg677ter mutation, whereas four others had one of the following: Pro658 (1-bp del), Ser747 (1-bp del), Leu762-763 (5-bp del), and Tyr1053 (1-bp del). In Arg677ter RP1 heterozygotes, there was regional retinal variation in disease, with the far peripheral inferonasal retina being most vulnerable; central and superior temporal retinal regions were better preserved. The earliest manifestation of disease was rod dysfunction, detectable as reduced rod ERG photoresponse maximum amplitude, even in heterozygotes with otherwise normal clinical, functional, and OCT cross-sectional retinal imaging results. At disease stages when cone abnormalities were present, there was greater rod than cone dysfunction. Patients with the RP1 frameshift mutations showed similarities in phenotype to those with the Arg677ter mutation. Earliest disease expression of RP1 gene mutations causing adRP involves primarily rod photoreceptors, and there is a gradient of vulnerability of retinopathy with more pronounced effects in the inferonasal peripheral retina. At other disease stages, cone function is also affected, and severe retina-wide degeneration can occur. The nonpenetrance or minimal disease expression in some Arg677ter mutation-positive heterozygotes suggests important roles for modifier genes or environmental factors in RP1-related disease.

  10. Erythropoietin Slows Photoreceptor Cell Death in a Mouse Model of Autosomal Dominant Retinitis Pigmentosa.

    PubMed

    Rex, Tonia S; Kasmala, Lorraine; Bond, Wesley S; de Lucas Cerrillo, Ana M; Wynn, Kristi; Lewin, Alfred S

    2016-01-01

    To test the efficacy of systemic gene delivery of a mutant form of erythropoietin (EPO-R76E) that has attenuated erythropoietic activity, in a mouse model of autosomal dominant retinitis pigmentosa. Ten-day old mice carrying one copy of human rhodopsin with the P23H mutation and both copies of wild-type mouse rhodopsin (hP23H RHO+/-,mRHO+/+) were injected into the quadriceps with recombinant adeno-associated virus (rAAV) carrying either enhanced green fluorescent protein (eGFP) or EpoR76E. Visual function (electroretinogram) and retina structure (optical coherence tomography, histology, and immunohistochemistry) were assessed at 7 and 12 months of age. The outer nuclear layer thickness decreased over time at a slower rate in rAAV.EpoR76E treated as compared to the rAAV.eGFP injected mice. There was a statistically significant preservation of the electroretinogram at 7, but not 12 months of age. Systemic EPO-R76E slows death of the photoreceptors and vision loss in hP23H RHO+/-,mRHO+/+ mice. Treatment with EPO-R76E may widen the therapeutic window for retinal degeneration patients by increasing the number of viable cells. Future studies might investigate if co-treatment with EPO-R76E and gene replacement therapy is more effective than gene replacement therapy alone.

  11. Erythropoietin Slows Photoreceptor Cell Death in a Mouse Model of Autosomal Dominant Retinitis Pigmentosa

    PubMed Central

    Kasmala, Lorraine; Bond, Wesley S.; de Lucas Cerrillo, Ana M.; Wynn, Kristi; Lewin, Alfred S.

    2016-01-01

    Purpose To test the efficacy of systemic gene delivery of a mutant form of erythropoietin (EPO-R76E) that has attenuated erythropoietic activity, in a mouse model of autosomal dominant retinitis pigmentosa. Methods Ten-day old mice carrying one copy of human rhodopsin with the P23H mutation and both copies of wild-type mouse rhodopsin (hP23H RHO+/-,mRHO+/+) were injected into the quadriceps with recombinant adeno-associated virus (rAAV) carrying either enhanced green fluorescent protein (eGFP) or EpoR76E. Visual function (electroretinogram) and retina structure (optical coherence tomography, histology, and immunohistochemistry) were assessed at 7 and 12 months of age. Results The outer nuclear layer thickness decreased over time at a slower rate in rAAV.EpoR76E treated as compared to the rAAV.eGFP injected mice. There was a statistically significant preservation of the electroretinogram at 7, but not 12 months of age. Conclusions Systemic EPO-R76E slows death of the photoreceptors and vision loss in hP23H RHO+/-,mRHO+/+ mice. Treatment with EPO-R76E may widen the therapeutic window for retinal degeneration patients by increasing the number of viable cells. Future studies might investigate if co-treatment with EPO-R76E and gene replacement therapy is more effective than gene replacement therapy alone. PMID:27299810

  12. Coping strategies to manage stress related to vision loss and fluctuations in retinitis pigmentosa

    PubMed Central

    Bittner, Ava K.; Edwards, Lori; George, Maureen

    2010-01-01

    Background Vision loss in retinitis pigmentosa (RP) is a slowly progressive and inexorable threat to patients’ independence. It is not surprising that RP patients, many of whom are young when diagnosed, are at high risk for stress related to their vision loss. To address these issues, eye care providers need to be aware of what coping strategies RP patients use to successfully manage their vision loss. Methods We held focus groups with eight legally blind RP patients to help us better understand how they cope with the stress that is generated from their progressive vision loss and fluctuations in vision. Focus group sessions were audiotaped and resulting notes were coded using conventional qualitative analytic techniques. Results Two themes were identified: 1) “kicking and screaming” captured the ways in which RP patients fight to maintain their independence in the face of worsening vision; and 2) “there are so many worse things” describes how RP patients keep their vision loss in perspective. These RP patients demonstrated high levels of resiliency. In particular, they often used humor as a coping mechanism. Conclusions Understanding the ways in which RP patients manage their gradual, impending vision loss may lead to improved quality of care for this patient population. PMID:20591747

  13. Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosa

    PubMed Central

    Ikeda, Hanako Ohashi; Sasaoka, Norio; Koike, Masaaki; Nakano, Noriko; Muraoka, Yuki; Toda, Yoshinobu; Fuchigami, Tomohiro; Shudo, Toshiyuki; Iwata, Ayana; Hori, Seiji; Yoshimura, Nagahisa; Kakizuka, Akira

    2014-01-01

    Neuroprotection may prevent or forestall the progression of incurable eye diseases, such as retinitis pigmentosa, one of the major causes of adult blindness. Decreased cellular ATP levels may contribute to the pathology of this eye disease and other neurodegenerative diseases. Here we describe small compounds (Kyoto University Substances, KUSs) that were developed to inhibit the ATPase activity of VCP (valosin-containing protein), the most abundant soluble ATPase in the cell. Surprisingly, KUSs did not significantly impair reported cellular functions of VCP but nonetheless suppressed the VCP-dependent decrease of cellular ATP levels. Moreover, KUSs, as well as exogenous ATP or ATP-producing compounds, e.g. methylpyruvate, suppressed endoplasmic reticulum stress, and demonstrably protected various types of cultured cells from death, including several types of retinal neuronal cells. We then examined their in vivo efficacies in rd10, a mouse model of retinitis pigmentosa. KUSs prevented photoreceptor cell death and preserved visual function. These results reveal an unexpected, crucial role of ATP consumption by VCP in determining cell fate in this pathological context, and point to a promising new neuroprotective strategy for currently incurable retinitis pigmentosa. PMID:25096051

  14. Novel VCP modulators mitigate major pathologies of rd10, a mouse model of retinitis pigmentosa.

    PubMed

    Ikeda, Hanako Ohashi; Sasaoka, Norio; Koike, Masaaki; Nakano, Noriko; Muraoka, Yuki; Toda, Yoshinobu; Fuchigami, Tomohiro; Shudo, Toshiyuki; Iwata, Ayana; Hori, Seiji; Yoshimura, Nagahisa; Kakizuka, Akira

    2014-08-06

    Neuroprotection may prevent or forestall the progression of incurable eye diseases, such as retinitis pigmentosa, one of the major causes of adult blindness. Decreased cellular ATP levels may contribute to the pathology of this eye disease and other neurodegenerative diseases. Here we describe small compounds (Kyoto University Substances, KUSs) that were developed to inhibit the ATPase activity of VCP (valosin-containing protein), the most abundant soluble ATPase in the cell. Surprisingly, KUSs did not significantly impair reported cellular functions of VCP but nonetheless suppressed the VCP-dependent decrease of cellular ATP levels. Moreover, KUSs, as well as exogenous ATP or ATP-producing compounds, e.g. methylpyruvate, suppressed endoplasmic reticulum stress, and demonstrably protected various types of cultured cells from death, including several types of retinal neuronal cells. We then examined their in vivo efficacies in rd10, a mouse model of retinitis pigmentosa. KUSs prevented photoreceptor cell death and preserved visual function. These results reveal an unexpected, crucial role of ATP consumption by VCP in determining cell fate in this pathological context, and point to a promising new neuroprotective strategy for currently incurable retinitis pigmentosa.

  15. Mutations in SCAPER cause autosomal recessive retinitis pigmentosa with intellectual disability.

    PubMed

    Tatour, Yasmin; Sanchez-Navarro, Iker; Chervinsky, Elana; Hakonarson, Hakon; Gawi, Haithum; Tahsin-Swafiri, Saoud; Leibu, Rina; Lopez-Molina, Maria Isabel; Fernandez-Sanz, Guillermo; Ayuso, Carmen; Ben-Yosef, Tamar

    2017-08-09

    Retinitis pigmentosa (RP) is the most common form of inherited retinal dystrophy, with a worldwide prevalence of 1 in 4000 persons. While in most cases of RP, the disease is limited to the eye (non-syndromic), over 40 forms of syndromic RP have been described. To identify the genetic basis for syndromic RP in three unrelated families from Israel and Spain. Whole exome sequencing was conducted in one Israeli and two Spanish families segregating autosomal recessive RP with intellectual disability. Complete ophthalmic examination included best-corrected visual acuity, funduscopy, optical coherence tomography, fluorescein angiography, flash visual evoked potentials, and electroretinography. Reverse transcription (RT)-PCR and immunostaining were used to examine the spatial and temporal expression pattern of SCAPER. In all patients, biallelic SCAPER mutations were observed. Clinically, patients with SCAPER mutations show signs of typical RP. In addition, they have mild to moderate intellectual disability and attention-deficit/hyperactivity disorder. SCAPER was found to be ubiquitously expressed in a wide range of human tissues, including retina and brain. Furthermore, RT-PCR analysis revealed that in both mouse eye and brain, Scaper is expressed as early as embryonic day 14. In the mouse retina, SCAPER is located in multiple layers, including the retinal pigment epithelium, photoreceptor outer and inner segments, the inner plexiform layer and the ganglion cell layer. Deleterious SCAPER mutations were identified in four patients from three unrelated families of different ethnic backgrounds, thereby confirming the involvement of this gene in the aetiology of autosomal recessive syndromic RP. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  16. Using the rd1 mouse to understand functional and anatomical retinal remodelling and treatment implications in retinitis pigmentosa: A review.

    PubMed

    Kalloniatis, M; Nivison-Smith, L; Chua, J; Acosta, M L; Fletcher, E L

    2016-09-01

    Retinitis Pigmentosa (RP) reflects a range of inherited retinal disorders which involve photoreceptor degeneration and retinal pigmented epithelium dysfunction. Despite the multitude of genetic mutations being associated with the RP phenotype, the clinical and functional manifestations of the disease remain the same: nyctalopia, visual field constriction (tunnel vision), photopsias and pigment proliferation. In this review, we describe the typical clinical phenotype of human RP and review the anatomical and functional remodelling which occurs in RP determined from studies in the rd/rd (rd1) mouse. We also review studies that report a slowing down or show an acceleration of retinal degeneration and finally we provide insights on the impact retinal remodelling may have in vision restoration strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Yearly rates of rod and cone functional loss in retinitis pigmentosa and cone-rod dystrophy.

    PubMed

    Birch, D G; Anderson, J L; Fish, G E

    1999-02-01

    To provide the first measures of the relative rates of rod and cone functional loss in patients with retinitis pigmentosa (RP) or cone-rod dystrophy (CRD). Five-year, prospective natural history study. Ninety-six patients (67 with RP and 29 with CRD) retaining measurable rod-mediated visual function and 5 normal subjects were tested at baseline and annually for 4 consecutive years. Tests of visual function included visual acuity, dark-adaptation thresholds, dark-adapted static perimetry, and rod and cone computer-averaged electroretinograms (ERGs), which were obtained over a range of retinal illuminances. Intervisit variability for each measure was obtained in a subset of patients who were tested twice within a 2-month interval and was used to determine whether an individual patient had shown progression, regression, or no change over a particular study interval. Over a 4-year interval, a significant number of patients with RP (60%) and CRD (62%) showed a decline in cone ERG amplitude. For rod ERG amplitude, the percentage of patients with RP or CRD showing progression was 64% and 45%, respectively. Although visual acuity, dark-adapted threshold, and rod visual field area also declined significantly over the 4-year period, the mean rate of change and the numbers of patients showing progression on these measures were lower than those for ERG measures. On specialized ERG testing, the yearly change in rod ERG threshold in RP was greater than the yearly change in cone ERG threshold, and the rate of progression varied significantly among inheritance types. For patients with CRD, the yearly change in rod threshold was comparable to the yearly change in cone ERG threshold. This study helps to define the natural progression of rod-mediated and cone-mediated functional loss in patients with RP and CRD.

  18. A novel mitochondrial mutation m.8989G>C associated with neuropathy, ataxia, retinitis pigmentosa - the NARP syndrome.

    PubMed

    Duno, Morten; Wibrand, Flemming; Baggesen, Kirsten; Rosenberg, Thomas; Kjaer, Niels; Frederiksen, Anja L

    2013-02-25

    The archetypal NARP syndrome is almost exclusively associated with the m.8993T>C/G mutation in the sixth subunit of the mitochondrial ATP synthase, whereas other mutations in the MT-ATP6 gene primarily associate with Leigh syndrome or Leber's hereditary optic neuropathy (LHON). We report a novel mitochondrial point mutation, m.8989G>C, in a patient presenting with neuropathy, ataxia and retinitis pigmentosa constituting the classical NARP phenotype. This mutation alters the amino acid right next to canonical NARP mutation. We suggest that classic NARP syndrome relates to a defined dysfunction of p.MT-ATP6.

  19. A Novel Method for Quantitative Serial Autofluorescence Analysis in Retinitis Pigmentosa Using Image Characteristics

    PubMed Central

    Jolly, Jasleen K.; Wagner, Siegfried K.; Moules, Jonathan; Gekeler, Florian; Webster, Andrew R.; Downes, Susan M.; MacLaren, Robert E.

    2016-01-01

    Purpose Identifying potential biomarkers for disease progression in retinitis pigmentosa (RP) is highly relevant now that gene therapy and other treatments are in clinical trial. Here we report a novel technique for analysis of short-wavelength autofluorescence (AF) imaging to quantify defined regions of AF in RP patients. Methods Fifty-five–degree AF images were acquired from 12 participants with RP over a 12-month period. Of these, five were identified as having a hyperfluorescent annulus. A standard Cartesian coordinate system was superimposed on images with the fovea as the origin and eight bisecting lines traversing the center at 45 degrees to each other. Spatial extraction software was programmed to highlight pixels corresponding to varying degrees of percentile fluorescence such that the parafoveal AF ring was mapped. Distance between the fovea and midpoint of the AF ring was measured. Percentage of low luminance areas was utilized as a measure of atrophy. Results The hyperfluorescent ring was most accurately mapped using the 70th percentile of fluorescence. Both the AF ring and peripheral hypofluorescence showed robust repeatability at all time points noted (P = 0.93). Conclusions Both a hypofluorescent ring and retinal pigment epithelium atrophy were present on a significant proportion of RP patients and were consistently mapped over a 12-month period. There is potential extrapolation of this methodology to wide-field imaging as well as other retinal dystrophies. This anatomical change may provide a useful anatomical biomarker for assessing treatment end points in RP. Translational Relevance Spatial extraction software can be a valuable tool in the assessment of ophthalmic imaging data. PMID:27933220

  20. Correlation of fundus autofluorescence with photoreceptor morphology and functional changes in eyes with retinitis pigmentosa.

    PubMed

    Wakabayashi, Taku; Sawa, Miki; Gomi, Fumi; Tsujikawa, Motokazu

    2010-08-01

    To assess and correlate fundus autofluorescence (FAF) characteristics with photoreceptor morphology and functional features in eyes with retinitis pigmentosa (RP). Thirty-four eyes of 17 patients with RP were examined. We compared FAF images obtained by confocal scanning laser ophthalmoscopy with Spectral-domain optical coherence tomography (SD-OCT) and retinal function assessed by microperimetry. Normal FAF surrounded by a ring of increased FAF at the macular area was detected in 32 (94%) eyes. The diameter of the normal FAF was correlated significantly with the preserved area of the photoreceptor inner segment and outer segment (IS/OS) junction on SD-OCT (R=0.939, p<0.001). The area outside the ring was associated with loss of IS/OS junction and external limiting membrane (ELM). The ring of increased FAF demarcated the border between the central retina with preservation of the IS/OS junction and ELM, and the adjacent eccentric retina with loss of these bands. In two eyes of one patient, there was no preservation of normal FAF at the macula and the photoreceptor IS/OS junction was not detected on SD-OCT. The mean retinal sensitivity derived from microperimetry was correlated significantly with the area of normal FAF (R=0.929, p=0.007) and the preserved area of the IS/OS junction (R=0.851, p=0.032). Ten eyes had progressive reduction in size of the normal FAF inside the ring accompanied by decreased area of preserved IS/OS during 3.1 years. FAF appears to reflect the integrity of the photoreceptor layer. It may serve as a secondary outcome measure for novel therapeutic strategies for RP.

  1. RP2 phenotype and pathogenetic correlations in X-linked retinitis pigmentosa.

    PubMed

    Jayasundera, Thiran; Branham, Kari E H; Othman, Mohammad; Rhoades, William R; Karoukis, Athanasios J; Khanna, Hemant; Swaroop, Anand; Heckenlively, John R

    2010-07-01

    To assess the phenotype of patients with X-linked retinitis pigmentosa (XLRP) with RP2 mutations and to correlate the findings with their genotype. Six hundred eleven patients with RP were screened for RP2 mutations. From this screen, 18 patients with RP2 mutations were evaluated clinically with standardized electroretinography, Goldmann visual fields, and ocular examinations. In addition, 7 well-documented cases from the literature were used to augment genotype-phenotype correlations. Of 11 boys younger than 12 years, 10 (91%) had macular involvement and 9 (82%) had best-corrected visual acuity worse than 20/50. Two boys from different families (aged 8 and 12 years) displayed a choroideremia-like fundus, and 9 boys (82%) were myopic (mean error, -7.97 diopters [D]). Of 10 patients with electroretinography data, 9 demonstrated severe rod-cone dysfunction. All 3 female carriers had macular atrophy in 1 or both eyes and were myopic (mean, -6.23 D). All 9 nonsense and frameshift and 5 of 7 missense mutations (71%) resulted in severe clinical presentations. Screening of the RP2 gene should be prioritized in patients younger than 16 years characterized by X-linked inheritance, decreased best-corrected visual acuity (eg, >20/40), high myopia, and early-onset macular atrophy. Patients exhibiting a choroideremia-like fundus without choroideremia gene mutations should also be screened for RP2 mutations. An identifiable phenotype for RP2-XLRP aids in clinical diagnosis and targeted genetic screening.

  2. Autosomal Recessive Retinitis Pigmentosa Due To ABCA4 Mutations: Clinical, Pathologic, and Molecular Characterization

    PubMed Central

    Mullins, Robert F.; Kuehn, Markus H.; Radu, Roxana A.; Enriquez, G. Stephanie; East, Jade S.; Schindler, Emily I.; Travis, Gabriel H.; Stone, Edwin M.

    2012-01-01

    Purpose. Autosomal recessive retinitis pigmentosa (ARRP) is a genetically heterogeneous condition characterized by progressive loss of retinal photoreceptor cells. In order to gain new insights into the pathogenesis of ARRP, we evaluated the morphological, biochemical, and gene expression changes in eyes from a human donor with ARRP due to mutations in the ABCA4 gene. Methods. Eyes were obtained postmortem from a donor with end-stage retinitis pigmentosa. The coding sequences of the RDS, RHO, and ABCA4 genes were screened for disease-causing mutations. Morphological changes in different regions of the retina were examined histologically, and levels of lipofuscin-associated bisretinoids were measured. Gene expression was examined in retinal/choroidal tissue using microarray analysis, and all parameters were compared to those in unaffected control donors. Results. Genetic analysis of the donor's DNA identified two mutations in the ABCA4 gene, IVS14+1G > C and Phe1440del1 cT, each on a separate allele. Morphological evaluation revealed complete loss of the outer nuclear layer, remodeling of the inner retina, loss of retinal vasculature, and regional neovascularization. The retinal pigment epithelium and choriocapillaris exhibited regional preservation. Microarray analysis revealed loss of photoreceptor cell-associated transcripts, with preservation of multiple genes expressed specifically in inner retinal neurons. Conclusions. The persistence of transcripts expressed by inner retinal neurons suggests that despite significant plasticity that occurs during retinal degeneration, bipolar cells and ganglion cells remain at least partially differentiated. Findings from this study suggest that some forms of therapy currently under investigation may have benefit even in advanced retinal degeneration. PMID:22395892

  3. Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa.

    PubMed

    Fernández-Sánchez, Laura; Lax, Pedro; Campello, Laura; Pinilla, Isabel; Cuenca, Nicolás

    2015-01-01

    Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas. In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina.

  4. Astrocytes and Müller Cell Alterations During Retinal Degeneration in a Transgenic Rat Model of Retinitis Pigmentosa

    PubMed Central

    Fernández-Sánchez, Laura; Lax, Pedro; Campello, Laura; Pinilla, Isabel; Cuenca, Nicolás

    2015-01-01

    Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina. PMID:26733810

  5. Retinitis pigmentosa: impact of different Pde6a point mutations on the disease phenotype.

    PubMed

    Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Jiao, Kangwei; Buena-Atienza, Elena; Sahaboglu, Ayse; Trifunović, Dragana; Balendran, Sukirthini; Koepfli, Tanja; Mühlfriedel, Regine; Schön, Christian; Biel, Martin; Heckmann, Angelique; Beck, Susanne C; Michalakis, Stylianos; Wissinger, Bernd; Seeliger, Mathias W; Paquet-Durand, François

    2015-10-01

    Mutations in the PDE6A gene can cause rod photoreceptors degeneration and the blinding disease retinitis pigmentosa (RP). While a number of pathogenic PDE6A mutations have been described, little is known about their impact on compound heterozygous situations and potential interactions of different disease-causing alleles. Here, we used a novel mouse model for the Pde6a R562W mutation in combination with an existing line carrying the V685M mutation to generate compound heterozygous Pde6a V685M/R562W animals, exactly homologous to a case of human RP. We compared the progression of photoreceptor degeneration in these compound heterozygous mice with the homozygous V685M and R562W mutants, and additionally with the D670G line that is known for a relatively mild phenotype. We investigated PDE6A expression, cyclic guanosine mono-phosphate accumulation, calpain and caspase activity, in vivo retinal function and morphology, as well as photoreceptor cell death and survival. This analysis confirms the severity of different Pde6a mutations and indicates that compound heterozygous mutants behave like intermediates of the respective homozygous situations. Specifically, the severity of the four different Pde6a situations may be categorized by the pace of photoreceptor degeneration: V685M (fastest) > V685M/R562W > R562W > D670G (slowest). While calpain activity was strongly increased in all four mutants, caspase activity was not. This points to the execution of non-apoptotic cell death and may lead to the identification of new targets for therapeutic interventions. For individual RP patients, our study may help to predict time-courses for Pde6a-related retinal degeneration and thereby facilitate the definition of a window-of-opportunity for clinical interventions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Mutation of CERKL, a Novel Human Ceramide Kinase Gene, Causes Autosomal Recessive Retinitis Pigmentosa (RP26)

    PubMed Central

    Tuson, Miquel; Marfany, Gemma; Gonzàlez-Duarte, Roser

    2004-01-01

    Retinitis pigmentosa (RP), the main cause of adult blindness, is a genetically heterogeneous disorder characterized by progressive loss of photoreceptors through apoptosis. Up to now, 39 genes and loci have been implicated in nonsyndromic RP, yet the genetic bases of >50% of the cases, particularly of the recessive forms, remain unknown. Previous linkage analysis in a Spanish consanguineous family allowed us to define a novel autosomal recessive RP (arRP) locus, RP26, within an 11-cM interval (17.4 Mb) on 2q31.2-q32.3. In the present study, we further refine the RP26 locus down to 2.5 Mb, by microsatellite and single-nucleotide polymorphism (SNP) homozygosity mapping. After unsuccessful mutational analysis of the nine genes initially reported in this region, a detailed gene search based on expressed-sequence-tag data was undertaken. We finally identified a novel gene encoding a ceramide kinase (CERKL), which encompassed 13 exons. All of the patients from the RP26 family bear a homozygous mutation in exon 5, which generates a premature termination codon. The same mutation was also characterized in another, unrelated, Spanish pedigree with arRP. Human CERKL is expressed in the retina, among other adult and fetal tissues. A more detailed analysis by in situ hybridization on adult murine retina sections shows expression of Cerkl in the ganglion cell layer. Ceramide kinases convert the sphingolipid metabolite ceramide into ceramide-1-phosphate, both key mediators of cellular apoptosis and survival. Ceramide metabolism plays an essential role in the viability of neuronal cells, the membranes of which are particularly rich in sphingolipids. Therefore, CERKL deficiency could shift the relative levels of the signaling sphingolipid metabolites and increase sensitivity of photoreceptor and other retinal cells to apoptotic stimuli. This is the first genetic report suggesting a direct link between retinal neurodegeneration in RP and sphingolipid-mediated apoptosis. PMID

  7. IMPG2-associated retinitis pigmentosa displays relatively early macular involvement.

    PubMed

    van Huet, Ramon A C; Collin, Rob W J; Siemiatkowska, Anna M; Klaver, Caroline C W; Hoyng, Carel B; Simonelli, Francesca; Khan, Muhammad I; Qamar, Raheel; Banin, Eyal; Cremers, Frans P M; Theelen, Thomas; den Hollander, Anneke I; van den Born, L Ingeborgh; Klevering, B Jeroen

    2014-05-29

    To provide the first detailed clinical description in patients with RP caused by recessive mutations in IMPG2. This international collaborative study includes 17 RP patients with inherited retinal disease caused by mutations in IMPG2. The patients were clinically (re-)examined, including extensive medical history taking, slit-lamp biomicroscopy, ophthalmoscopy, perimetry, ERG, optical coherence tomography (OCT), fundus autofluorescence (FAF) imaging, fundus photography, and color vision tests. The main outcome measures included mean age at onset, initial symptom, best-corrected visual acuity, fundus appearance, perimetry results, ERG responses, OCT images, FAF imaging, color vision test reports and DNA sequence variants. The mean age at onset was 10.5 years (range, 4-20 years). Initial symptoms included night blindness in 59% of patients, a decreased visual acuity in 35%, and visual field loss in 6%. Fundus abnormalities were typical of RP: optic disc pallor, attenuated vessels, bone spicules, and generalized atrophy of the retina and choriocapillaris. Additionally, we observed macular abnormalities in all patients, ranging from subtle mottling of the macular pigment epithelium (two patients) and a bull's eye maculopathy (seven patients) to macular chorioretinal atrophy (seven patients). Mutations in IMPG2 cause a severe form of RP with symptoms manifesting in the first 2 decades of life. IMPG2-associated RP is frequently accompanied by macular involvement, ranging from mild pigment alterations to profound chorioretinal atrophy. The resulting decrease in central vision in combination with the severe tunnel vision leads to severe visual impairment in patients with IMPG2-associated RP. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  8. Retinitis Pigmentosa and Bilateral Idiopathic Demyelinating Optic Neuritis in a 6-Year-Old Boy with OFD1 Gene Mutation

    PubMed Central

    Wang, Xun; Zheng, Cong; Liu, Wen

    2017-01-01

    To identify the cause of a sudden binocular vision decrease in patients with retinitis pigmentosa and bilateral idiopathic demyelinating optic neuritis is difficult, but early diagnosis and treatment significantly improve the prognosis. Here, we report a 6-year-old boy with a progressive binocular vision decrease in 38 days. The patient had a history of night blindness, a mottled retina without pigmentation, extinguished electroretinographic response, tritanopia, and an absent ellipsoid zone outside the macula fovea by optical coherence tomography in both eyes. His condition was diagnosed as retinitis pigmentosa (RP) with idiopathic demyelinating optic neuritis (IDON). After corticosteroid therapy, visual acuity recovered to OD: 0.5 and OS: 0.4. Genetic analysis revealed a G985S variant in the oral-facial-digital syndrome 1 gene. Ophthalmologists should pay attention to the existence of other complications in patients with RP who suffer a sudden decrease in vision. A gene survey can help clarify this diagnosis. To our knowledge, this is the first report of a patient with RP and ON, as well as genetic testing results. Nevertheless, the pathogenicity of the variant needs further confirmation. PMID:28191358

  9. Phospholipid Bicelles Improve the Conformational Stability of Rhodopsin Mutants Associated with Retinitis Pigmentosa.

    PubMed

    Dong, Xiaoyun; Ramon, Eva; Herrera-Hernández, María Guadalupe; Garriga, Pere

    2015-08-11

    Mutations in the visual photoreceptor rhodopsin are the cause of the retinal degenerative disease retinitis pigmentosa. Some naturally occurring mutations can lead to protein conformational instability. Two such mutations, N55K and G90V, in the first and second transmembrane helices of the receptor, have been associated with sector and classical retinitis pigmentosa, respectively, and showed enhanced thermal sensitivity. We have carefully analyzed the effect of phospholipid bicelles on the stability and ligand binding properties of these two mutants and compared it with those of the detergent-solubilized samples. We have used a phospholipid bilayer consisting of 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC). We find that DMPC/DHPC bicelles dramatically increase the thermal stability of the rhodopsin mutants G90V and N55K. The chromophore stability and regeneration of the mutants were also increased in bicelles when compared to their behavior in a dodecyl maltoside detergent solution. The retinal release process was slowed in bicelles, and chromophore entry, after illumination, was improved for the G90V mutant but not for N55K. Furthermore, fluorescence spectroscopy measurements showed that bicelles allowed more exogenous retinal binding to the photoactivated G90V mutant than in a detergent solution. In contrast, N55K could not reposition any chromophore either in the detergent or in bicelles. The results demonstrate that DMPC/DHPC bicelles can counteract the destabilizing effect of the disease-causing mutations and can modulate the structural changes in the ensuing receptor photoactivation in a distinct specific manner for different retinitis pigmentosa mutant phenotypes.

  10. Long-term decline of central cone function in retinitis pigmentosa evaluated by focal electroretinogram.

    PubMed

    Falsini, Benedetto; Galli-Resta, Lucia; Fadda, Antonello; Ziccardi, Lucia; Piccardi, Marco; Iarossi, Giancarlo; Resta, Giovanni

    2012-11-19

    We evaluated long-term changes of central cone-mediated function in retinitis pigmentosa (RP) patients by recording focal electroretinograms (fERG). A cohort of 43 RP patients was followed from 4 to 16 years (average follow-up 9.3 years, average 10 examinations/patient) by recording the fERG response to a flickering uniform red field overlaying the central 18° of visual field (VF). Statistical censoring led to a reduced dataset of 32 patients (autosomal dominant 9, recessive 5, sporadic 5, x-linked 1, Usher II 12), from which long-term decay rates were estimated by global fitting of individual fERG amplitude time-curves. Long-term follow-up of central cone FERG amplitude showed two main features: short-term variability and long-term decline. fERG short-term variability range was 0.14 to 0.2 log units. Mean yearly decay rate of central fERG was 5.6% (95% confidence interval [CI] 4%-7%). Yearly decline depended on inheritance pattern, being significantly greater in autosomal recessive and sporadic compared to autosomal dominant RP. The degree of central cone fERG decline was unrelated to the size of the residual VF. The decline of central cone function is significantly slower than global cone function decline in RP. Central cone fERG loss is independent of residual VF.

  11. Emotional Health of People with Visual Impairment Caused by Retinitis Pigmentosa

    PubMed Central

    Latham, Keziah; Baranian, Mohammad; Timmis, Matthew; Pardhan, Shahina

    2015-01-01

    Purpose To understand the emotional difficulties associated with living with the ocular condition Retinitis Pigmentosa, and to examine the functioning of a self-report instrument used to assess this construct. Methods The difficulty of goals and tasks in the emotional health domain of the Dutch ICF Activity Inventory were rated by 166 people with Retinitis Pigmentosa in a cross-sectional study. Demographic factors were also assessed. Results Responses to the 23 emotional health tasks were Rasch analysed and could be used to form either one 20 item overview scale with some multidimensionality, or three unidimensional subscales addressing feelings (4 items), communicating visual loss (5 items) and fatigue (7 items). The most difficult individual tasks related to communicating visual loss to other people, and dealing with feelings such as frustration, anxiety and stress. The use of mobility aids and female gender were associated with increased difficulty with emotional health, explaining 19% of the variance in the overview scale. Conclusions The emotional health domain of the Dutch ICF Activity Inventory is a valid tool to assess emotional difficulties arising from visual loss. Interventions to aid people with Retinitis Pigmentosa deal with emotional difficulties should particularly address communicating vision loss effectively to others and coping with negative feelings. PMID:26713624

  12. Correlation between macular blood flow and central visual sensitivity in retinitis pigmentosa.

    PubMed

    Murakami, Yusuke; Ikeda, Yasuhiro; Akiyama, Masato; Fujiwara, Kota; Yoshida, Noriko; Nakatake, Shunji; Notomi, Shoji; Nabeshima, Takahiro; Hisatomi, Toshio; Enaida, Hiroshi; Ishibashi, Tatsuro

    2015-12-01

    To investigate the changes in macular blood flow and the correlation between those changes and central visual function in patients with retinitis pigmentosa (RP). The mean blur rate (MBR), a quantitative blurring index of the laser speckle pattern that represents retinal and choroidal blood flow, was measured by laser speckle flowgraphy. Mean blur rate values in the macular area were compared between 70 patients with RP and 28 control subjects. The relationships between MBR on the one hand and, on the other, visual acuity (VA), mean deviation (MD) and averaged macular sensitivity of static perimetry tests (Humphrey Filed Analyzer, the central 10-2 program) were analysed in patients with RP. Macular MBR was decreased to 75% in patients with RP compared with control subjects (p < 0.0001, Student's t-test). Spearman's rank testing showed that macular MBR was significantly correlated with VA (r = -0.261, p = 0.0299), MD values (r = 0.438, p = 0.0002) and averaged macular sensitivity at the central 4 and 12 points of static perimetry tests (r = 0.426 and 0.442, p = 0.0003 and 0.0002, respectively). Multivariable-adjusted analysis confirmed that MBR was independently associated with MD (p = 0.0002) and macular sensitivity at the central 4 and 12 points (p < 0.0001 and 0.0002, respectively). Decreased macular blood flow was associated with reduced macular visual sensitivity in patients with RP. Although the cause-effect relationships remain to be elucidated, these findings suggest that vascular defects may be involved in the pathogenesis of RP such as central vision loss. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  13. Hypomorphic mutations in TRNT1 cause retinitis pigmentosa with erythrocytic microcytosis

    PubMed Central

    DeLuca, Adam P.; Whitmore, S. Scott; Barnes, Jenna; Sharma, Tasneem P.; Westfall, Trudi A.; Scott, C. Anthony; Weed, Matthew C.; Wiley, Jill S.; Wiley, Luke A.; Johnston, Rebecca M.; Schnieders, Michael J.; Lentz, Steven R.; Tucker, Budd A.; Mullins, Robert F.; Scheetz, Todd E.; Stone, Edwin M.; Slusarski, Diane C.

    2016-01-01

    Retinitis pigmentosa (RP) is a highly heterogeneous group of disorders characterized by degeneration of the retinal photoreceptor cells and progressive loss of vision. While hundreds of mutations in more than 100 genes have been reported to cause RP, discovering the causative mutations in many patients remains a significant challenge. Exome sequencing in an individual affected with non-syndromic RP revealed two plausibly disease-causing variants in TRNT1, a gene encoding a nucleotidyltransferase critical for tRNA processing. A total of 727 additional unrelated individuals with molecularly uncharacterized RP were completely screened for TRNT1 coding sequence variants, and a second family was identified with two members who exhibited a phenotype that was remarkably similar to the index patient. Inactivating mutations in TRNT1 have been previously shown to cause a severe congenital syndrome of sideroblastic anemia, B-cell immunodeficiency, recurrent fevers and developmental delay (SIFD). Complete blood counts of all three of our patients revealed red blood cell microcytosis and anisocytosis with only mild anemia. Characterization of TRNT1 in patient-derived cell lines revealed reduced but detectable TRNT1 protein, consistent with partial function. Suppression of trnt1 expression in zebrafish recapitulated several features of the human SIFD syndrome, including anemia and sensory organ defects. When levels of trnt1 were titrated, visual dysfunction was found in the absence of other phenotypes. The visual defects in the trnt1-knockdown zebrafish were ameliorated by the addition of exogenous human TRNT1 RNA. Our findings indicate that hypomorphic TRNT1 mutations can cause a recessive disease that is almost entirely limited to the retina. PMID:26494905

  14. Hypomorphic mutations in TRNT1 cause retinitis pigmentosa with erythrocytic microcytosis.

    PubMed

    DeLuca, Adam P; Whitmore, S Scott; Barnes, Jenna; Sharma, Tasneem P; Westfall, Trudi A; Scott, C Anthony; Weed, Matthew C; Wiley, Jill S; Wiley, Luke A; Johnston, Rebecca M; Schnieders, Michael J; Lentz, Steven R; Tucker, Budd A; Mullins, Robert F; Scheetz, Todd E; Stone, Edwin M; Slusarski, Diane C

    2016-01-01

    Retinitis pigmentosa (RP) is a highly heterogeneous group of disorders characterized by degeneration of the retinal photoreceptor cells and progressive loss of vision. While hundreds of mutations in more than 100 genes have been reported to cause RP, discovering the causative mutations in many patients remains a significant challenge. Exome sequencing in an individual affected with non-syndromic RP revealed two plausibly disease-causing variants in TRNT1, a gene encoding a nucleotidyltransferase critical for tRNA processing. A total of 727 additional unrelated individuals with molecularly uncharacterized RP were completely screened for TRNT1 coding sequence variants, and a second family was identified with two members who exhibited a phenotype that was remarkably similar to the index patient. Inactivating mutations in TRNT1 have been previously shown to cause a severe congenital syndrome of sideroblastic anemia, B-cell immunodeficiency, recurrent fevers and developmental delay (SIFD). Complete blood counts of all three of our patients revealed red blood cell microcytosis and anisocytosis with only mild anemia. Characterization of TRNT1 in patient-derived cell lines revealed reduced but detectable TRNT1 protein, consistent with partial function. Suppression of trnt1 expression in zebrafish recapitulated several features of the human SIFD syndrome, including anemia and sensory organ defects. When levels of trnt1 were titrated, visual dysfunction was found in the absence of other phenotypes. The visual defects in the trnt1-knockdown zebrafish were ameliorated by the addition of exogenous human TRNT1 RNA. Our findings indicate that hypomorphic TRNT1 mutations can cause a recessive disease that is almost entirely limited to the retina.

  15. Gelsolin dysfunction causes photoreceptor loss in induced pluripotent cell and animal retinitis pigmentosa models.

    PubMed

    Megaw, Roly; Abu-Arafeh, Hashem; Jungnickel, Melissa; Mellough, Carla; Gurniak, Christine; Witke, Walter; Zhang, Wei; Khanna, Hemant; Mill, Pleasantine; Dhillon, Baljean; Wright, Alan F; Lako, Majlinda; Ffrench-Constant, Charles

    2017-08-16

    Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) cause X-linked RP (XLRP), an untreatable, inherited retinal dystrophy that leads to premature blindness. RPGR localises to the photoreceptor connecting cilium where its function remains unknown. Here we show, using murine and human induced pluripotent stem cell models, that RPGR interacts with and activates the actin-severing protein gelsolin, and that gelsolin regulates actin disassembly in the connecting cilium, thus facilitating rhodopsin transport to photoreceptor outer segments. Disease-causing RPGR mutations perturb this RPGR-gelsolin interaction, compromising gelsolin activation. Both RPGR and Gelsolin knockout mice show abnormalities of actin polymerisation and mislocalisation of rhodopsin in photoreceptors. These findings reveal a clinically-significant role for RPGR in the activation of gelsolin, without which abnormalities in actin polymerisation in the photoreceptor connecting cilia cause rhodopsin mislocalisation and eventual retinal degeneration in XLRP.Mutations in the Retinitis Pigmentosa GTPase Regulator (RPGR) cause retinal dystrophy, but how this arises at a molecular level is unclear. Here, the authors show in induced pluripotent stem cells and mouse knockouts that RPGR mediates actin dynamics in photoreceptors via the actin-severing protein, gelsolin.

  16. Clinical and Rehabilitative Management of Retinitis Pigmentosa: Up-to-Date

    PubMed Central

    Parmeggiani, Francesco; Sato, Giovanni; De Nadai, Katia; Romano, Mario R; Binotto, Andrea; Costagliola, Ciro

    2011-01-01

    The term retinitis pigmentosa (RP) indicates a heterogeneous group of genetic rare ocular diseases in which either rods or cones are prevalently damaged. RP represents the most common hereditary cause of blindness in people from 20 to 60 years old. In general, the different RP forms consist of progressive photo-receptorial neuro-degenerations, which are characterized by variable visual disabilities and considerable socio-sanitary burden. Sometimes, RP patients do not become visually impaired or legally blind until their 40-50 years of age and/or maintain a quite acceptable sight for all their life. Other individuals with RP become completely blind very early or in middle childhood. Although there is no treatment that can effectively cure RP, in some case-series the disease’s progression seems to be reducible by specific preventive approaches. In the most part of RP patients, the quality of vision can be considerably increased by means of nanometer-controlled filters. In the present review, the main aspects of the routine clinical and rehabilitative managements for RP patients are described, particularly focusing on the importance of specific referral Centers to practice a real multidisciplinary governance of these dramatic diseases. PMID:22131870

  17. Autosomal recessive posterior column ataxia with retinitis pigmentosa caused by novel mutations in the FLVCR1 gene.

    PubMed

    Shaibani, Aziz; Wong, Lee-Jun; Wei Zhang, Victor; Lewis, Richard Alan; Shinawi, Marwan

    2015-01-01

    Posterior column ataxia with retinitis pigmentosa (PCARP) is an autosomal recessive disorder characterized by severe sensory ataxia, muscle weakness and atrophy, and progressive pigmentary retinopathy. Recently, mutations in the FLVCR1 gene were described in four families with this condition. We investigated the molecular basis and studied the phenotype of PCARP in a new family. The proband is a 33-year-old woman presented with sensory polyneuropathy and retinitis pigmentosa (RP). The constellation of clinical findings with normal metabolic and genetic evaluation, including mitochondrial DNA (mtDNA) analysis and normal levels of phytanic acid and vitamin E, prompted us to seek other causes of our patient's condition. Sequencing of FLVCR1 in the proband and targeted mutation testing in her two affected siblings revealed two novel variants, c.1547G > A (p.R516Q) and c.1593+5_+8delGTAA predicted, respectively, to be highly conserved throughout evolution and affecting the normal splicing, therefore, deleterious. This study supports the pathogenic role of FLVCR1 in PCARP and expands the molecular and clinical spectra of PCARP. We show for the first time that nontransmembrane domain (TMD) mutations in the FLVCR1 can cause PCARP, suggesting different mechanisms for pathogenicity. Our clinical data reveal that impaired sensation can be part of the phenotypic spectrum of PCARP. This study along with previously reported cases suggests that targeted sequencing of the FLVCR1 gene should be considered in patients with severe sensory ataxia, RP, and peripheral sensory neuropathy.

  18. Treatment of cystoid macular edema secondary to retinitis pigmentosa: A systematic review.

    PubMed

    Bakthavatchalam, Malini; Lai, Frank H P; Rong, Shi Song; Ng, Danny S; Brelen, Marten E

    2017-10-04

    There are various treatments for cystoid macular edema (CME) secondary to retinitis pigmentosa (RP); however, the evidence for these treatments has not been previously systematically reviewed. Our review that includes 23 studies shows that oral carbonic anhydrase inhibitors (CAI) (including acetazolamide, methazolamide) and topical CAI (dorzolamide and brinzolamide) are effective first line treatments. In patients unresponsive to CAI treatment, intravitreal steroids (triamcinolone acetonide and sustained-release dexamethasone implant), oral corticosteroid (Deflazacort), intravitreal anti-vascular endothelial growth factor agents (ranibizumab and bevacizumab), grid laser photocoagulation, pars plana vitrectomy, or ketorolac were also effective in improving CME secondary to RP. Oral acetazolamide has the strongest clinical basis for treatment and was superior to topical dorzolamide. Rebound of CME was commonly seen in the long term, regardless of the choice of treatment. Oral acetazolamide should be the first line treatment in CME secondary to RP. Topical dorzolamide is an appropriate alternative in patients intolerant to adverse effects of oral acetazolamide. More studies are required to investigate the management of rebound CME. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Novel genetic and neuropathological insights in neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP).

    PubMed

    Claeys, Kristl G; Abicht, Angela; Häusler, Martin; Kleinle, Stephanie; Wiesmann, Martin; Schulz, Jörg B; Horvath, Rita; Weis, Joachim

    2016-08-01

    Neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) is caused by m.8993T>G/C mutations in the mitochondrial adenosine triphosphate synthase subunit 6 gene (MT-ATP6). Traditionally, heteroplasmy levels between 70% and 90% lead to NARP, and >90% result in Leigh syndrome. In this study we report a 30-year-old man with NARP and m.8993T>G in MT-ATP6. Although the patient carried the mutation in homoplasmic state in blood with similarly high levels in urine (94%) and buccal swab (92%), he presented with NARP and not the expected, more severe Leigh phenotype. The mutation could not be detected in any of the 3 analyzed tissues of the mother, indicating a large genetic shift between mother and offspring. Nerve biopsy revealed peculiar endoneurial Schwann cell nuclear accumulations, clusters of concentrically arranged Schwann cells devoid of myelinated axons, and degenerated mitochondria. We emphasize the phenotypic variability of the m.8993T>G MT-ATP6 mutation and the need for caution in predictive counseling in such patients. Muscle Nerve 54: 328-333, 2016. © 2016 Wiley Periodicals, Inc.

  20. Towards isolation of the gene for X-linked retinitis pigmentosa (RP3)

    SciTech Connect

    Dry, K.L.; Aldred, M.A.; Hardwick, L.J.

    1994-09-01

    Until recently the region of interest containing the gene for X-linked retinitis pigmentosa (RP3) was thought to lie between CYBB (Xp21.1) and the proximal end of the deletion in patient BB (JBBprox). This region was thought to span 100-150 kb. Here we present new mapping data to show that the distance between the 5{prime} (most proximal) end of CYBB and JBBprox is only 50 kb. Recently Roux et al. (1994) have described the isolation of a gene within this region but this showed no disease-associated changes. Further evidence from mapping the deletion in patient NF (who suffered from McLead`s syndrome and CGD but not RP) and from linkage analysis of our RP3 families with a new dinucleotide repeat suggests that the gene must extend proximally from JBBprox. In order to extend the region of search we have constructed a YAC contig spanning 800 kb to OTC. We are continuing our search for the RP3 gene using a variety of strategies including exon trapping and cDNA enrichment as well as direct screening of cDNA libraries with subclones from this region.

  1. Visual acuity and 10 degrees automated static perimetry in eyes with retinitis pigmentosa.

    PubMed

    Abe, Keitetsu; Iijima, Hiroyuki; Hirakawa, Hirohide; Tsukahara, Yasushi; Toda, Yoshiki

    2002-01-01

    In a previous study we demonstrated that the progression of the disease retinitis pigmentosa (RP) can be readily monitored by the mean deviation (MD) measured by Humphrey central 10-2 perimetry, which assesses the sensitivity distribution in the macular area in eyes affected by RP. In the present study, we investigated whether the 10 degrees perimetric results could predict the time of declining visual acuity in eyes with RP in a cross-sectional study. Humphrey 10-2 perimetry results and visual acuity were studied in the right eyes of 69 patients with typical RP. Patients whose eyes had cataract, glaucoma, cystoid macular edema, or other complications affecting vision were excluded. Eyes with an MD of -15 dB or greater had almost normal visual acuity. Various degrees of visual acuity loss were observed in eyes with an MD of less than -15 dB. In the 35 eyes with an MD of less than -15 dB, visual acuity correlated well with the corrected pattern standard deviation (CPSD), which is the measure of the degree to which the shape of the measured field departs from the age-corrected normal reference field. In the absence of complications, many eyes with RP may experience acuity loss after the field constriction reaches an MD of less than -15 dB. The CPSD may be used as an indicator of acuity because eyes showing a lower CPSD tend to have greater loss of acuity among eyes with an equivalent MD value.

  2. Genotyping microarray: Mutation screening in Spanish families with autosomal dominant retinitis pigmentosa

    PubMed Central

    García-Hoyos, María; Cortón, Marta; Ávila-Fernández, Almudena; Riveiro-Álvarez, Rosa; Giménez, Ascensión; Hernan, Inma; Carballo, Miguel; Ayuso, Carmen

    2012-01-01

    Purpose Presently, 22 genes have been described in association with autosomal dominant retinitis pigmentosa (adRP); however, they explain only 50% of all cases, making genetic diagnosis of this disease difficult and costly. The aim of this study was to evaluate a specific genotyping microarray for its application to the molecular diagnosis of adRP in Spanish patients. Methods We analyzed 139 unrelated Spanish families with adRP. Samples were studied by using a genotyping microarray (adRP). All mutations found were further confirmed with automatic sequencing. Rhodopsin (RHO) sequencing was performed in all negative samples for the genotyping microarray. Results The adRP genotyping microarray detected the mutation associated with the disease in 20 of the 139 families with adRP. As in other populations, RHO was found to be the most frequently mutated gene in these families (7.9% of the microarray genotyped families). The rate of false positives (microarray results not confirmed with sequencing) and false negatives (mutations in RHO detected with sequencing but not with the genotyping microarray) were established, and high levels of analytical sensitivity (95%) and specificity (100%) were found. Diagnostic accuracy was 15.1%. Conclusions The adRP genotyping microarray is a quick, cost-efficient first step in the molecular diagnosis of Spanish patients with adRP. PMID:22736939

  3. Mutations in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) cause the RP10 form of autosomal dominant retinitis pigmentosa

    PubMed Central

    Bowne, Sara J.; Sullivan, Lori S.; Blanton, Susan H.; Cepko, Constance L.; Blackshaw, Seth; Birch, David G.; Hughbanks-Wheaton, Dianna; Heckenlively, John R.; Daiger, Stephen P.

    2008-01-01

    Autosomal dominant retinitis pigmentosa (adRP) is a heterogeneous set of progressive retinopathies caused by several distinct genes. One locus, the RP10 form of adRP, maps to human chromosome 7q31.1 and may account for 5–10% of adRP cases among Americans and Europeans. We identified two American families with the RP10 form of adRP by linkage mapping and used these families to reduce the linkage interval to 3.45 Mb between the flanking markers D7S686 and RP-STR8. Sequence and transcript analysis identified 54 independent genes within this region, at least 10 of which are retinal-expressed and thus candidates for the RP10 gene. A screen of retinal transcripts comparing retinas from normal mice to retinas from crx−/crx− knockout mice (with poorly differentiated photoreceptors) demonstrated a 6-fold reduction in one candidate, inosine monophosphate dehydrogenase 1 (IMPDH1; EC 1.1.1.205). Since many of the genes known to cause retinitis pigmentosa are under CRX control in photoreceptors, IMPDH1 became a high-priority candidate for mutation screening. DNA sequencing of affected individuals from the two American RP10 families revealed a GAC→AAC transition in codon 226 substituting an asparagine for an aspartic acid in both families. The identical mutation was also found in a British RP10 family. The Asp226Asn missense mutation is present in all affected individuals tested and absent from unaffected controls. The aspartic acid at codon 226 is conserved in all IMPDH genes, in all species examined, including bacteria, suggesting that this mutation is highly deleterious. Subsequent screening of probands from 60 other adRP families revealed an additional family with this mutation, confirming its association with retinitis pigmentosa and the relatively high frequency of this mutation. Another IMPDH1 substitution, Val268Ile, was also observed in this cohort of patients but not in controls. IMPDH1 is a ubiquitously expressed enzyme, functioning as a homotetramer, which

  4. Mutations in the inosine monophosphate dehydrogenase 1 gene (IMPDH1) cause the RP10 form of autosomal dominant retinitis pigmentosa.

    PubMed

    Bowne, Sara J; Sullivan, Lori S; Blanton, Susan H; Cepko, Constance L; Blackshaw, Seth; Birch, David G; Hughbanks-Wheaton, Dianna; Heckenlively, John R; Daiger, Stephen P

    2002-03-01

    Autosomal dominant retinitis pigmentosa (adRP) is a heterogeneous set of progressive retinopathies caused by several distinct genes. One locus, the RP10 form of adRP, maps to human chromosome 7q31.1 and may account for 5-10% of adRP cases among Americans and Europeans. We identified two American families with the RP10 form of adRP by linkage mapping and used these families to reduce the linkage interval to 3.45 Mb between the flanking markers D7S686 and RP-STR8. Sequence and transcript analysis identified 54 independent genes within this region, at least 10 of which are retinal-expressed and thus candidates for the RP10 gene. A screen of retinal transcripts comparing retinas from normal mice to retinas from crx-/crx- knockout mice (with poorly differentiated photoreceptors) demonstrated a 6-fold reduction in one candidate, inosine monophosphate dehydrogenase 1 (IMPDH1; EC 1.1.1.205). Since many of the genes known to cause retinitis pigmentosa are under CRX control in photoreceptors, IMPDH1 became a high-priority candidate for mutation screening. DNA sequencing of affected individuals from the two American RP10 families revealed a GAC-->AAC transition in codon 226 substituting an asparagine for an aspartic acid in both families. The identical mutation was also found in a British RP10 family. The Asp226Asn missense mutation is present in all affected individuals tested and absent from unaffected controls. The aspartic acid at codon 226 is conserved in all IMPDH genes, in all species examined, including bacteria, suggesting that this mutation is highly deleterious. Subsequent screening of probands from 60 other adRP families revealed an additional family with this mutation, confirming its association with retinitis pigmentosa and the relatively high frequency of this mutation. Another IMPDH1 substitution, Val268Ile, was also observed in this cohort of patients but not in controls. IMPDH1 is a ubiquitously expressed enzyme, functioning as a homotetramer, which

  5. Identification of a novel mutation in the PRCD gene causing autosomal recessive retinitis pigmentosa in a Turkish family

    PubMed Central

    Pach, Johanna; Kohl, Susanne; Gekeler, Florian

    2013-01-01

    Purpose Progressive rod-cone degeneration (PRCD) is a canine form of autosomal recessive photoreceptor degeneration and serves as an animal model for human retinitis pigmentosa (RP). To date, only two RP-causing mutations of the PRCD gene have been reported in humans. We found a novel mutation in PRCD (c.52C>T, p.R18X) in three siblings affected by RP and present detailed morphologic and functional parameters. Methods A complete ophthalmological examination was performed including psychophysical tests (best-corrected visual acuity, Lanthony Panel D-15 color vision test, and visual field) and electrophysiology (ganzfeld and multifocal electroretinogram). Additionally, color and infrared fundus photography, autofluorescence, and spectral domain optical coherence tomography recordings were performed. Genomic DNA of the three affected individuals was analyzed with high-throughput sequencing for all RP-related genes in a diagnostic set-up. Results We identified a novel homozygous mutation in PRCD (c.52C>T, p.R18X) with diagnostic high-throughput panel sequencing. All three patients showed an advanced stage of retinitis pigmentosa with reduced visual acuity (mean: 20/80), small residual visual fields (mean for target III4e: 1134.35 deg2), and non-detectable electrophysiological responses. Myopia, posterior subcapsular cataract, bone spicule-like pigmentation, and attenuated arterioles were typical findings. Interestingly, bull’s eye maculopathy due to patchy retinal pigment epithelium atrophy was also present in all patients. The mean central retinal thickness observed in optical coherence tomography was 148 µm. Conclusions The identification of a third mutation in PRCD confirms its role in the pathogenesis of RP. Clinical findings were in line with the morphological changes observed in previous studies. Bull’s eye maculopathy seems to be a hallmark of RP due to mutations in the PRCD gene. PMID:23805042

  6. Mutations in IMPG2, Encoding Interphotoreceptor Matrix Proteoglycan 2, Cause Autosomal-Recessive Retinitis Pigmentosa

    PubMed Central

    Bandah-Rozenfeld, Dikla; Collin, Rob W.J.; Banin, Eyal; Ingeborgh van den Born, L.; Coene, Karlien L.M.; Siemiatkowska, Anna M.; Zelinger, Lina; Khan, Muhammad I.; Lefeber, Dirk J.; Erdinest, Inbar; Testa, Francesco; Simonelli, Francesca; Voesenek, Krysta; Blokland, Ellen A.W.; Strom, Tim M.; Klaver, Caroline C.W.; Qamar, Raheel; Banfi, Sandro; Cremers, Frans P.M.; Sharon, Dror; den Hollander, Anneke I.

    2010-01-01

    Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases caused by progressive degeneration of the photoreceptor cells. Using autozygosity mapping, we identified two families, each with three affected siblings sharing large overlapping homozygous regions that harbored the IMPG2 gene on chromosome 3. Sequence analysis of IMPG2 in the two index cases revealed homozygous mutations cosegregating with the disease in the respective families: three affected siblings of Iraqi Jewish ancestry displayed a nonsense mutation, and a Dutch family displayed a 1.8 kb genomic deletion that removes exon 9 and results in the absence of seven amino acids in a conserved SEA domain of the IMPG2 protein. Transient transfection of COS-1 cells showed that a construct expressing the wild-type SEA domain is properly targeted to the plasma membrane, whereas the mutant lacking the seven amino acids appears to be retained in the endoplasmic reticulum. Mutation analysis in ten additional index cases that were of Dutch, Israeli, Italian, and Pakistani origin and had homozygous regions encompassing IMPG2 revealed five additional mutations; four nonsense mutations and one missense mutation affecting a highly conserved phenylalanine residue. Most patients with IMPG2 mutations showed an early-onset form of RP with progressive visual-field loss and deterioration of visual acuity. The patient with the missense mutation, however, was diagnosed with maculopathy. The IMPG2 gene encodes the interphotoreceptor matrix proteoglycan IMPG2, which is a constituent of the interphotoreceptor matrix. Our data therefore show that mutations in a structural component of the interphotoreceptor matrix can cause arRP. PMID:20673862

  7. Exome sequencing identifies compound heterozygous mutations in CYP4V2 in a pedigree with retinitis pigmentosa.

    PubMed

    Wang, Yun; Guo, Liheng; Cai, Su-Ping; Dai, Meizhi; Yang, Qiaona; Yu, Wenhan; Yan, Naihong; Zhou, Xiaomin; Fu, Jin; Guo, Xinwu; Han, Pengfei; Wang, Jun; Liu, Xuyang

    2012-01-01

    Retinitis pigmentosa (RP) is a heterogeneous group of progressive retinal degenerations characterized by pigmentation and atrophy in the mid-periphery of the retina. Twenty two subjects from a four-generation Chinese family with RP and thin cornea, congenital cataract and high myopia is reported in this study. All family members underwent complete ophthalmologic examinations. Patients of the family presented with bone spicule-shaped pigment deposits in retina, retinal vascular attenuation, retinal and choroidal dystrophy, as well as punctate opacity of the lens, reduced cornea thickness and high myopia. Peripheral venous blood was obtained from all patients and their family members for genetic analysis. After mutation analysis in a few known RP candidate genes, exome sequencing was used to analyze the exomes of 3 patients III2, III4, III6 and the unaffected mother II2. A total of 34,693 variations shared by 3 patients were subjected to several filtering steps against existing variation databases. Identified variations were verified in the rest family members by PCR and Sanger sequencing. Compound heterozygous c.802-8_810del17insGC and c.1091-2A>G mutations of the CYP4V2 gene, known as genetic defects for Bietti crystalline corneoretinal dystrophy, were identified as causative mutations for RP of this family.

  8. Wide-Field Fundus Autofluorescence for Retinitis Pigmentosa and Cone/Cone-Rod Dystrophy.

    PubMed

    Oishi, Akio; Oishi, Maho; Ogino, Ken; Morooka, Satoshi; Yoshimura, Nagahisa

    2016-01-01

    Retinitis pigmentosa and cone/cone-rod dystrophy are inherited retinal diseases characterized by the progressive loss of rod and/or cone photoreceptors. To evaluate the status of rod/cone photoreceptors and visual function, visual acuity and visual field tests, electroretinogram, and optical coherence tomography are typically used. In addition to these examinations, fundus autofluorescence (FAF) has recently garnered attention. FAF visualizes the intrinsic fluorescent material in the retina, which is mainly lipofuscin contained within the retinal pigment epithelium. While conventional devices offer limited viewing angles in FAF, the recently developed Optos machine enables recording of wide-field FAF. With wide-field analysis, an association between abnormal FAF areas and visual function was demonstrated in retinitis pigmentosa and cone-rod dystrophy. In addition, the presence of "patchy" hypoautofluorescent areas was found to be correlated with symptom duration. Although physicians should be cautious when interpreting wide-field FAF results because the peripheral parts of the image are magnified significantly, this examination method provides previously unavailable information.

  9. Functional Cone Rescue by RdCVF Protein in a Dominant Model of Retinitis Pigmentosa

    PubMed Central

    Yang, Ying; Mohand-Said, Saddek; Danan, Aude; Simonutti, Manuel; Fontaine, Valérie; Clerin, Emmanuelle; Picaud, Serge; Léveillard, Thierry; Sahel, José-Alain

    2009-01-01

    In retinitis pigmentosa (RP), a majority of causative mutations affect genes solely expressed in rods; however, cone degeneration inevitably follows rod cell loss. Following transplantation and in vitro studies, we demonstrated the role of photoreceptor cell paracrine interactions and identified a Rod-derived Cone Viability Factor (RdCVF), which increases cone survival. In order to establish the clinical relevance of such mechanism, we assessed the functional benefit afforded by the injection of this factor in a frequent type of rhodopsin mutation, the P23H rat. In this model of autosomal dominant RP, RdCVF expression decreases in parallel with primary rod degeneration, which is followed by cone loss. RdCVF protein injections induced an increase in cone cell number and, more important, a further increase in the corresponding electroretinogram (ERG). These results indicate that RdCVF can not only rescue cones but also preserve significantly their function. Interestingly, the higher amplitude of the functional versus the survival effect of RdCVF on cones indicates that RdCVF is acting more directly on cone function. The demonstration at the functional level of the therapeutic potential of RdCVF in the most frequent of dominant RP mutations paves the way toward the use of RdCVF for preserving central vision in many RP patients. PMID:19277021

  10. Whole exome sequencing of a dominant retinitis pigmentosa family identifies a novel deletion in PRPF31.

    PubMed

    Villanueva, Adda; Willer, Jason R; Bryois, Julien; Dermitzakis, Emmanouil T; Katsanis, Nicholas; Davis, Erica E

    2014-04-07

    Mutations at some retinitis pigmentosa (RP) loci are associated with variable penetrance and expressivity, exacerbating diagnostic challenges. The purpose of this study was to dissect the genetic underpinnings of nonsyndromic RP with variable age of onset in a large Mexican family. We ascertained members of a large, multigenerational pedigree using a complete ophthalmic examination. We performed whole exome sequencing on two affected first cousins, an obligate carrier, and a married-in spouse. Confirmatory sequencing of candidate variants was performed in the entire pedigree, as well as genotyping and mRNA studies to investigate expression changes in the causal locus. We identified a 14-base pair (bp) deletion in PRPF31, a gene implicated previously in autosomal dominant (ad) RP. The mutation segregated with the phenotype of all 10 affected females, but also was present in six asymptomatics (two females and four males). Studies in patient cells showed that the penetrance/expressivity of the PRPF31 deletion allele was concordant with the expression levels of wild-type message. However, neither the known PRPF31 modulators nor cis-eQTLs within 1 Mb of the locus could account for the variable expression of message or the clinical phenotype. We have identified a novel 14-bp deletion in PRPF31 as the genetic driver of adRP in a large Mexican family that exhibits nonpenetrance and variable expressivity, known properties of this locus. However, our studies intimate the presence of additional loci that can modify PRPF31 expression.

  11. Acute unilateral vision loss with optic disc oedema in retinitis pigmentosa.

    PubMed

    Patil-Chhablani, Preeti; Tyagi, Mudit; Kekunnaya, Ramesh; Narayanan, Raja

    2015-08-03

    A 36-year-old woman presented with acute vision loss and was found to have disc oedema and retinitis pigmentosa (RP). She presented with a history of acute, painless vision loss in her left eye over a period of 10 days. Her best-corrected visual acuity was 20/50, N6 in the right eye (OD) and 20/160, N6 in the left eye (OS). She was found to have a swollen optic disc and the examination of her fundus showed changes suggestive of RP. The diagnosis of RP was confirmed by electroretinogram, and after ruling out demyelinating changes in the central nervous system and other possible infectious causes of papillitis, she was treated with intravenous steroids followed by a course of oral steroid therapy. Following treatment, her visual acuity improved to 20/60. Acute vision loss may occur in patients with RP and prompt steroid therapy may result in partial visual recovery. 2015 BMJ Publishing Group Ltd.

  12. A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution.

    PubMed

    Otto, Edgar; Hoefele, Julia; Ruf, Rainer; Mueller, Adelheid M; Hiller, Karl S; Wolf, Matthias T F; Schuermann, Maria J; Becker, Achim; Birkenhäger, Ralf; Sudbrak, Ralf; Hennies, Hans C; Nürnberg, Peter; Hildebrandt, Friedhelm

    2002-11-01

    Nephronophthisis (NPHP) comprises a group of autosomal recessive cystic kidney diseases, which constitute the most frequent genetic cause for end-stage renal failure in children and young adults. The most prominent histologic feature of NPHP consists of development of renal fibrosis, which, in chronic renal failure of any origin, represents the pathogenic event correlated most strongly to loss of renal function. Four gene loci for NPHP have been mapped to chromosomes 2q13 (NPHP1), 9q22 (NPHP2), 3q22 (NPHP3), and 1p36 (NPHP4). At all four loci, linkage has also been demonstrated in families with the association of NPHP and retinitis pigmentosa, known as "Senior-Løken syndrome" (SLS). Identification of the gene for NPHP type 1 had revealed nephrocystin as a novel docking protein, providing new insights into mechanisms of cell-cell and cell-matrix signaling. We here report identification of the gene (NPHP4) causing NPHP type 4, by use of high-resolution haplotype analysis and by demonstration of nine likely loss-of-function mutations in six affected families. NPHP4 encodes a novel protein, nephroretinin, that is conserved in evolution--for example, in the nematode Caenorhabditis elegans. In addition, we demonstrate two loss-of-function mutations of NPHP4 in patients from two families with SLS. Thus, we have identified a novel gene with critical roles in renal tissue architecture and ophthalmic function.

  13. Long-term follow-up of a family with dominant X-linked retinitis pigmentosa.

    PubMed

    Wu, D M; Khanna, H; Atmaca-Sonmez, P; Sieving, P A; Branham, K; Othman, M; Swaroop, A; Daiger, S P; Heckenlively, J R

    2010-05-01

    To document the progression of disease in male and female members of a previously described family with X-linked dominant retinitis pigmentosa (RP) caused by a de novo insertion after nucleotide 173 in exon ORF15 of RPGR. The clinical records of 19 members of family UTAD054 were reviewed. Their evaluations consisted of confirmation of family history, standardised electroretinograms (ERGs), Goldmann visual fields, and periodic ophthalmological examinations over a 23-year period. Male members of family UTAD054 had non-recordable to barely recordable ERGs from early childhood. The males showed contracted central fields and developed more severe retinopathy than the females. The female members showed a disease onset delayed to teenage years, recordable but diminishing photopic and scotopic ERG amplitudes in a cone-rod pattern, progressive loss and often asymmetric visual fields, and diffuse atrophic retinopathy with fewer pigment deposits compared with males. This insertion mutation in the RPGR exon ORF15 is associated with a RP phenotype that severely affects males early and females by 30 years of age, and is highly penetrant in female members. Families with dominant-acting RPGR mutations may be mistaken to have an autosomal mode of inheritance resulting in an incorrect prediction of recurrence risk and prognosis. Broader recognition of X-linked RP forms with dominant inheritance is necessary to facilitate appropriate counselling of these patients.

  14. Two novel mutations in PRPF3 causing autosomal dominant retinitis pigmentosa

    PubMed Central

    Zhong, Zilin; Yan, Min; Sun, Wan; Wu, Zehua; Han, Liyun; Zhou, Zheng; Zheng, Fang; Chen, Jianjun

    2016-01-01

    Retinitis pigmentosa (RP) is a heterogeneous set of hereditary eye diseases, characterized by selective death of photoreceptor cells in the retina, resulting in progressive visual impairment. Approximately 20–40% of RP cases are autosomal dominant RP (ADRP). In this study, a Chinese ADRP family previously localized to the region between D1S2819 and D1S2635 was sequenced via whole-exome sequencing and a variant c.1345C > G (p.R449G) was identified in PRPF3. The Sanger sequencing was performed in probands of additional 95 Chinese ADRP families to investigate the contribution of PRPF3 to ADRP in Chinese population and another variant c.1532A > C (p.H511P) was detected in one family. These two variants, co-segregate with RP in two families respectively and both variants are predicted to be pathological. This is the first report about the spectrum of PRPF3 mutations in Chinese population, leading to the identification of two novel PRPF3 mutations. Only three clustered mutations in PRPF3 have been identified so far in several populations and all are in exon 11. Our study expands the spectrum of PRPF3 mutations in RP. We also demonstrate that PRPF3 mutations are responsible for 2.08% of ADRP families in this cohort indicating that PRPF3 mutations might be relatively rare in Chinese ADRP patients. PMID:27886254

  15. Next-generation sequencing-based molecular diagnosis of 35 Hispanic retinitis pigmentosa probands

    PubMed Central

    Zhang, Qi; Xu, Mingchu; Verriotto, Jennifer D.; Li, Yumei; Wang, Hui; Gan, Lin; Lam, Byron L.; Chen, Rui

    2016-01-01

    Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal diseases. The prevalence of RP and the mutation spectrum vary across populations. Hispanic people account for approximately 17% of the United States population, and the genetic etiologies of RP of this ethnic group still remain not well defined. Utilizing next-generation sequencing (NGS), we screened mutations in known retinal disease-causing genes in an RP cohort of 35 unrelated Hispanic probands from the Miami area. We achieved a solving rate of 66% and identified 15 novel putative pathogenic mutations, including a frequent founder mutation disrupting PRPF31 splicing. Our data show that the mutation spectrum of Hispanic RP receives a significant impact from disease-causing alleles of Spanish origin and may also contain population-specific alleles. PMID:27596865

  16. CNTF Gene Therapy Confers Lifelong Neuroprotection in a Mouse Model of Human Retinitis Pigmentosa

    PubMed Central

    Lipinski, Daniel M; Barnard, Alun R; Singh, Mandeep S; Martin, Chris; Lee, Edward J; Davies, Wayne I L; MacLaren, Robert E

    2015-01-01

    The long-term outcome of neuroprotection as a therapeutic strategy for preventing cell death in neurodegenerative disorders remains unknown, primarily due to slow disease progression and the inherent difficulty of assessing neuronal survival in vivo. Employing a murine model of retinal disease, we demonstrate that ciliary neurotrophic factor (CNTF) confers life-long protection against photoreceptor degeneration. Repetitive retinal imaging allowed the survival of intrinsically fluorescent cone photoreceptors to be quantified in vivo. Imaging of the visual cortex and assessment of visually-evoked behavioral responses demonstrated that surviving cones retain function and signal correctly to the brain. The mechanisms underlying CNTF-mediated neuroprotection were explored through transcriptome analysis, revealing widespread upregulation of proteolysis inhibitors, which may prevent cellular/extracellular matrix degradation and complement activation in neurodegenerative diseases. These findings provide insights into potential novel therapeutic avenues for diseases such as retinitis pigmentosa and amyotrophic lateral sclerosis, for which CNTF has been evaluated unsuccessfully in clinical trials. PMID:25896245

  17. ERG and other discriminators between advanced hydroxychloroquine retinopathy and retinitis pigmentosa.

    PubMed

    Nair, Archana A; Marmor, Michael F

    2017-06-01

    To study whether the ERG and other clinical findings help to distinguish between advanced hydroxychloroquine (HCQ) retinopathy and pericentral or diffuse retinitis pigmentosa (RP) with similar fundus appearance. We conducted a retrospective analysis of patients with advanced HCQ retinopathy (n = 11), pericentral RP (n = 8) and diffuse RP (n = 8). Pericentral RP was defined as having limited fundus damage and relatively normal flicker ERG time-to-peak. Diffuse RP had typical loss of the rod ERG and flicker timing delay. All patients showed reduced amplitude of the ISCEV responses in the full-field electroretinogram (ERG). Aspects of history, visual field results, fundus appearance, fundus autofluorescence and ocular coherence tomography were also compared. Relative to pericentral RP, patients with HCQ toxicity showed delayed flicker ERG time-to-peak and lower ERG amplitudes, particularly combined rod-cone responses. Relative to diffuse RP, most HCQ toxicity patients had some preserved rod ERG response, and there was no obvious predilection for rod over cone damage. In addition, patients with HCQ toxicity usually lacked markers of long-standing degeneration such as bone spicule figures or severe loss of peripheral field. History of familial disease and long-standing night blindness were specific to RP. While the early signs of HCQ damage are typically regional in the posterior pole, advanced disease is characteristically diffuse (unlike pericentral RP). This is appropriate for a systemic toxin, as is the finding that rods and cones were both affected in the ERG to a similar degree (unlike genetic rod-cone dystrophies). For patients with severe HCQ exposure and some of our discriminatory findings, and no family history or prior night blindness, HCQ toxicity is a sufficient diagnosis without invoking a second rare disease (Occam's razor).

  18. Efficacy of Column Scatter Plots for Presenting Retinitis Pigmentosa Phenotypes in a Japanese Cohort

    PubMed Central

    Ogino, Ken; Oishi, Akio; Oishi, Maho; Gotoh, Norimoto; Morooka, Satoshi; Sugahara, Masako; Hasegawa, Tomoko; Miyata, Manabu; Yoshimura, Nagahisa

    2016-01-01

    Purpose We evaluated the efficacy of column scatter plots to describe genotype–phenotype correlations in a Japanese cohort with retinitis pigmentosa (RP). Methods Clinical records of 121 patients with RP with identified causative mutations were reviewed. Visual acuity, central and peripheral visual fields, electroretinography (ERG), lens status, and measurements of optical coherence tomography were evaluated according to causative genes using column scatter plots. Values for three common genes (EYS, USH2A, and RHO) were compared statistically. Results All patients with PDE6B, PRPH2, and RPGR mutations, those 55 years old or younger with RP1L1 and USH2A mutations, and those 45 years old or younger with EYS and RHO mutations retained visual acuity of at least 0.1. All patients with RPGR mutations showed at least −20 dB mean deviation. Goldmann perimeter measures of 4/6 patients with RHO mutations showed remaining peripheral visual fields. Dark-adapted 0.01 and 3.0 ERGs were extinguished for most genes. Half of the patients with RHO RP maintained cone responses in light-adapted 3.0 and 3.0 flicker ERG. All patients with PRPH2, those 55 years old or younger with USH2A and RP1L1, and those 45 years old or younger with PDE6B and EYS mutations maintained subfoveal ellipsoid zones. No differences were identified between EYS and USH2A or RHO and USH2A. Conclusions Column scatter plots enabled comparisons of the associated severities and illustration of the ophthalmological measurements for every RP causative gene. Translational Relevance Analysis of mutations in specific genes may be helpful for determining visual prognoses in the clinical setting. PMID:26966640

  19. Neuroprotective effects of methyl 3,4 dihydroxybenzoate in a mouse model of retinitis pigmentosa.

    PubMed

    Zhang, Jia; Xu, Di; Ouyang, Huan; Hu, Songhui; Li, Ang; Luo, Huanmin; Xu, Ying

    2017-09-01

    Retinitis pigmentosa is a photoreceptor-degenerative disease that is currently untreatable and eventually causes blindness. Methyl 3,4 dihydroxybenzoate (MDHB) is a small molecule that exerts neuroprotective effects in vitro. The present study tests whether MDHB protects the retina of rd10 mice, a model of retinitis pigmentosa. MDHB or an equal volume of vehicle was intraperitoneally injected in rd10 mice daily from postnatal day 12 (P12) to P26. Retinal morphology was evaluated by immunostaining, and retinal function by electroretinogram (ERG) and by visual behavior. TUNEL, Iba1, GFAP staining and western blotting were applied to explore the neuroprotective mechanism of MDHB in retina. MDHB treatment significantly promoted photoreceptor survival and preserved cone morphology compared to the untreated animals. The visual behavior and ERG responses were also greatly enhanced in MDHB-treated rd10 mice. Mechanistically, following MDHB treatment, the number of TUNEL-positive cells was decreased in rd10 retina, and the expression of brain-derived neurotrophic factor (BDNF) protein and phosphorylated tropomyosin-related kinase B (TrkB) receptor were increased. Furthermore, blocking TrkB using the antagonist ANA-12 prevented the protective effect of MDHB on photoreceptor survival and structure. MDHB treatment also inhibited microglial activation and Muller cell gliosis in rd10 retina. In conclusion, MDHB treatment delays retinal degeneration in rd10 mice and preserves retinal structure and functions. These effects are likely mediated by the BDNF-TrkB pathway. Due to its neurotrophic effects and ability to reduce reactive gliosis, MDHB may be useful to treat degenerative diseases in retina and brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Whole exome sequencing identified novel CRB1 mutations in Chinese and Indian populations with autosomal recessive retinitis pigmentosa

    PubMed Central

    Yang, Yin; Yang, Yeming; Huang, Lulin; Zhai, Yaru; Li, Jie; Jiang, Zhilin; Gong, Bo; Fang, Hao; Kim, Ramasamy; Yang, Zhenglin; Sundaresan, Periasamy; Zhu, Xianjun; Zhou, Yu

    2016-01-01

    Retinitis pigmentosa (RP) is a leading cause of inherited blindness characterized by progressive degeneration of the retinal photoreceptor cells. This study aims to identify genetic mutations in a Chinese family RP-2236, an Indian family RP-IC-90 and 100 sporadic Indian individuals with autosomal recessive RP (arRP). Whole exome sequencing was performed on the index patients of RP-2236, RP-IC-90 and all of the 100 sporadic Indian patients. Direct Sanger sequencing was used to validate the mutations identified. Four novel mutations and one reported mutation in the crumbs homolog 1 (CRB1) gene, which has been known to cause severe retinal dystrophies, were identified. A novel homozygous splicing mutation c.2129-1G>C was found in the three patients In family RP-2236. A homozygous point mutation p.R664C was found in RP-IC-90. A novel homozygous mutation p.G1310C was identified in patient I-44, while novel compound heterozygous mutations p.N629D and p.A593T were found in patient I-7. All mutations described above were not present in the 1000 normal controls. In conclusion, we identified four novel mutations in CRB1 in a cohort of RP patients from the Chinese and Indian populations. Our data enlarges the CRB1 mutation spectrums and may provide new target loci for RP diagnose and treatment. PMID:27670293

  1. Low-dose-rate, low-dose irradiation delays neurodegeneration in a model of retinitis pigmentosa.

    PubMed

    Otani, Atsushi; Kojima, Hiroshi; Guo, Congrong; Oishi, Akio; Yoshimura, Nagahisa

    2012-01-01

    The existence of radiation hormesis is controversial. Several stimulatory effects of low-dose (LD) radiation have been reported to date; however, the effects on neural tissue or neurodegeneration remain unknown. Here, we show that LD radiation has a neuroprotective effect in mouse models of retinitis pigmentosa, a hereditary, progressive neurodegenerative disease that leads to blindness. Various LD radiation doses were administered to the eyes in a retinal degeneration mouse model, and their pathological and physiological effects were analyzed. LD gamma radiation in a low-dose-rate (LDR) condition rescues photoreceptor cell apoptosis both morphologically and functionally. The greatest effect was observed in a condition using 650 mGy irradiation and a 26 mGy/minute dose rate. Multiple rounds of irradiation strengthened this neuroprotective effect. A characteristic up-regulation (563%) of antioxidative gene peroxiredoxin-2 (Prdx2) in the LDR-LD-irradiated retina was observed compared to the sham-treated control retina. Silencing the Prdx2 using small-interfering RNA administration reduced the LDR-LD rescue effect on the photoreceptors. Our results demonstrate for the first time that LDR-LD irradiation has a biological effect in neural cells of living animals. The results support that radiation exhibits hormesis, and this effect may be applied as a novel therapeutic concept for retinitis pigmentosa and for other progressive neurodegenerative diseases regardless of the mechanism of degeneration involved.

  2. Clinical and genetic identification of a large chinese family with autosomal dominant retinitis pigmentosa.

    PubMed

    Yang, Yezhen; Tian, Di; Lee, Janet; Zeng, Jing; Zhang, Huiming; Chen, Siying; Guo, Hui; Xiong, Zhiming; Xia, Kun; Hu, Zhengmao; Luo, Jing

    2015-03-01

    Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by night blindness, progressive peripheral visual field loss, and loss of central vision. Fifty-three RP pathogenic genes are responsible for RP. Pre-mRNA processing factor 31(PRPF31) gene is the third most common cause of autosomal dominant retinitis pigmentosa (adRP), and so far more than 40 mutations in PRPF31 have been detected. To identify the underlying genetic defect in a five-generation Chinese family affected with adRP and to study the genotype-phenotype relationship of this family. Detailed clinical investigations were undertaken and peripheral blood samples were collected from 25 individuals. Microsatellite (STR) markers tightly linked to genes known to be responsible for adRP were selected for linkage analysis. Exons and adjacent splice junctions of the candidate gene were amplified and sequenced. This adRP family exhibited an incomplete penetrance of the RP phenotype. In affected individuals, age of disease onset was from infancy to 4 years of age. Typical RP features were associated with this mutation. Linkage analysis identified a maximum two-point LOD score of 3.20 with D19S418, which is close to PRPF31. A mutation PRPF31: (c.358-359 del AA) was identified by linkage analysis. A PRPF31 mutation was identified to be responsible for adRP in a large Chinese family. Our findings expand the mutation spectrum of RP in the Chinese population.

  3. Novel C8orf37 mutations cause retinitis pigmentosa in consanguineous families of Pakistani origin

    PubMed Central

    Ravesh, Zeinab; El Asrag, Mohammed E.; Weisschuh, Nicole; McKibbin, Martin; Reuter, Peggy; Watson, Christopher M.; Baumann, Britta; Poulter, James A.; Sajid, Sundus; Panagiotou, Evangelia S.; O’Sullivan, James; Abdelhamed, Zakia; Bonin, Michael; Soltanifar, Mehdi; Black, Graeme C.M.; Din, Muhammad Amin-ud; Toomes, Carmel; Ansar, Muhammad; Inglehearn, Chris F.; Wissinger, Bernd

    2015-01-01

    Purpose To investigate the molecular basis of retinitis pigmentosa in two consanguineous families of Pakistani origin with multiple affected members. Methods Homozygosity mapping and Sanger sequencing of candidate genes were performed in one family while the other was analyzed with whole exome next-generation sequencing. A minigene splicing assay was used to confirm the splicing defects. Results In family MA48, a novel homozygous nucleotide substitution in C8orf37, c.244–2A>C, that disrupted the consensus splice acceptor site of exon 3 was found. The minigene splicing assay revealed that this mutation activated a cryptic splice site within exon 3, causing a 22 bp deletion in the transcript that is predicted to lead to a frameshift followed by premature protein truncation. In family MA13, a novel homozygous null mutation in C8orf37, c.555G>A, p.W185*, was identified. Both mutations segregated with the disease phenotype as expected in a recessive manner and were absent in 8,244 unrelated individuals of South Asian origin. Conclusions In this report, we describe C8orf37 mutations that cause retinal dystrophy in two families of Pakistani origin, contributing further data on the phenotype and the spectrum of mutations in this form of retinitis pigmentosa. PMID:25802487

  4. Optical imaging of oxidative stress in retinitis pigmentosa (RP) in rodent model

    NASA Astrophysics Data System (ADS)

    Ghanian, Zahra; Maleki, Sepideh; Gopalakrishnan, Sandeep; Sepehr, Reyhaneh; Eells, Janis T.; Ranji, Mahsa

    2013-02-01

    Oxidative stress (OS), which increases during retinal degenerative disorders, contributes to photoreceptor cell loss. The objective of this study was to investigate the changes in the metabolic state of the eye tissue in rodent models of retinitis pigmentosa by using the cryofluorescence imaging technique. The mitochondrial metabolic coenzymes NADH and FADH2 are autofluorescent and can be monitored without exogenous labels using optical techniques. The NADH redox ratio (RR), which is the ratio of the fluorescence intensity of these fluorophores (NADH/FAD), was used as a quantitative diagnostic marker. The NADH RR was examined in an established rodent model of retinitis pigmentosa (RP), the P23H rat, and compared to that of control Sprague-Dawley (SD) rats and P23H NIR treated rats. Our results demonstrated 24% decrease in the mean NADH RR of the eyes from P23H transgenic rats compared to normal rats and 20% increase in the mean NADH RR of the eyes from the P23H NIR treated rats compared to P23H non-treated rats.

  5. The efficacy of microarray screening for autosomal recessive retinitis pigmentosa in routine clinical practice

    PubMed Central

    van Huet, Ramon A. C.; Pierrache, Laurence H.M.; Meester-Smoor, Magda A.; Klaver, Caroline C.W.; van den Born, L. Ingeborgh; Hoyng, Carel B.; de Wijs, Ilse J.; Collin, Rob W. J.; Hoefsloot, Lies H.

    2015-01-01

    Purpose To determine the efficacy of multiple versions of a commercially available arrayed primer extension (APEX) microarray chip for autosomal recessive retinitis pigmentosa (arRP). Methods We included 250 probands suspected of arRP who were genetically analyzed with the APEX microarray between January 2008 and November 2013. The mode of inheritance had to be autosomal recessive according to the pedigree (including isolated cases). If the microarray identified a heterozygous mutation, we performed Sanger sequencing of exons and exon–intron boundaries of that specific gene. The efficacy of this microarray chip with the additional Sanger sequencing approach was determined by the percentage of patients that received a molecular diagnosis. We also collected data from genetic tests other than the APEX analysis for arRP to provide a detailed description of the molecular diagnoses in our study cohort. Results The APEX microarray chip for arRP identified the molecular diagnosis in 21 (8.5%) of the patients in our cohort. Additional Sanger sequencing yielded a second mutation in 17 patients (6.8%), thereby establishing the molecular diagnosis. In total, 38 patients (15.2%) received a molecular diagnosis after analysis using the microarray and additional Sanger sequencing approach. Further genetic analyses after a negative result of the arRP microarray (n = 107) resulted in a molecular diagnosis of arRP (n = 23), autosomal dominant RP (n = 5), X-linked RP (n = 2), and choroideremia (n = 1). Conclusions The efficacy of the commercially available APEX microarray chips for arRP appears to be low, most likely caused by the limitations of this technique and the genetic and allelic heterogeneity of RP. Diagnostic yields up to 40% have been reported for next-generation sequencing (NGS) techniques that, as expected, thereby outperform targeted APEX analysis. PMID:25999674

  6. Molecular genetics of X-linked retinitis pigmentosa: Progress towards cloning the RP3 gene

    SciTech Connect

    Fujita, R.; Yan, D.; McHenry, C.

    1994-09-01

    Our goal is to identify the X-linked retinitis pigmentosa (XLRP) gene RP3. The location of RP3 is genetically delimited to a region of 1 Mb, distal to DXS140, CYBB and tctex-1-like gene and proximal to the gene OTC. It is currently thought that RP3 is within 40 kb of the proximal deletion breakpoint of a patient BB. However, a more proximal location of the gene, closer to OTC, is not ruled out. We initiated the isolation of the genomic region between DXS140 to OTC in YACs. One of the clones from DXS140 region (55B) is 460 kb and spans about 200 kb at each side of BB patient`s proximal breakpoint. It contains CYBB, tctex-1-like genes and two additional CpG islands. The 55B clone has been covered by cosmid and phage subclones. Another YAC clone from the OTC region (OTCC) spans about 1 Mb and contains at least 5 CpG islands. In situ hybridization performed with OTCC showed its location in Xp21; however, several derivative cosmids map to chromosome 7, indicating that it is a chimeric YAC. No overlap is evident between 55B and OTCC. We have isolated the YAC end-sequences and isolation of clones to close the gap is in progress. Cosmids are being used for screening eye tissue cDNA libraries, mainly from retina. Screening is done by hybridization to replica filters or by cDNA enrichment methods. Several cDNA clones have been isolated and are being characterized. Exon-amplification is also being used with the cosmids and phages. Genetic analysis is being performed to determine RP3 patients from clinically indistinguishable RP2, located in Xp11.23-p11.4, and to reduce the genetic distance of current flanking markers. For this we are analyzing a number of XLRP families with established markers in the region and with new microsatellites.

  7. [Retinitis pigmentosa: results of rhodopsin gene analysis in the Galician population].

    PubMed

    Blanco, M J; Capeans, C; Lareu, M V; Carracedo, A; Piñero, A; Santos, L; Copena, M J; Sánchez-Salorio, M

    2000-08-01

    Retinitis pigmentosa (RP) is the most prevalent inherited degeneration in the retina. The clinical manifestations are variable in terms of severity, age of onset and progression. The clinical variation is paralleled by genetic heterogeneity (more than 20 different loci have been described to date). The aim of this work was to identify mutations in rhodopsin gene and to determine the frequencies of the different genetic forms of RP in the Galician population. 47 previously diagnosed RP patients and their relatives were studied. Genetic forms of RP were identified by recording full family history and clinical examination. DNA samples from patients with RP and control individuals were screened for point mutations in the rhodopsin gene by using PCR SSCPs (Single Strand Conformation Polymorphisms) and direct sequencing in 36 unrelated nonsyndromic RP patients. We report the frequency distribution of the different genetic RP forms. In the SSCPs analysis of rhodopsin gene we found different mobility shifts: one variant in the 5'-untranslated region of the gen and one variant in the third intron. Direct sequencing revealed an A269-->G and an C3982-->T transitions, respectively. Additionally, we observed a single base change in codon 160 (C-->A) of this gene. Polymorphisms are commom findings in the exon 1 and 3 of rhodopsin gene. They are neutral variations and do not represent a change in the protein. No significant differences in the frecuencies of A269-->G and C3982-->T polymorphisms among the three groups of RP patients (ADRP, ARRP, Esporadic RP) and normal individuals were found. There was no significant deviation from Hardy-Weinberg's equilibrium in each genotype in any group.

  8. The efficacy of microarray screening for autosomal recessive retinitis pigmentosa in routine clinical practice.

    PubMed

    van Huet, Ramon A C; Pierrache, Laurence H M; Meester-Smoor, Magda A; Klaver, Caroline C W; van den Born, L Ingeborgh; Hoyng, Carel B; de Wijs, Ilse J; Collin, Rob W J; Hoefsloot, Lies H; Klevering, B Jeroen

    2015-01-01

    To determine the efficacy of multiple versions of a commercially available arrayed primer extension (APEX) microarray chip for autosomal recessive retinitis pigmentosa (arRP). We included 250 probands suspected of arRP who were genetically analyzed with the APEX microarray between January 2008 and November 2013. The mode of inheritance had to be autosomal recessive according to the pedigree (including isolated cases). If the microarray identified a heterozygous mutation, we performed Sanger sequencing of exons and exon-intron boundaries of that specific gene. The efficacy of this microarray chip with the additional Sanger sequencing approach was determined by the percentage of patients that received a molecular diagnosis. We also collected data from genetic tests other than the APEX analysis for arRP to provide a detailed description of the molecular diagnoses in our study cohort. The APEX microarray chip for arRP identified the molecular diagnosis in 21 (8.5%) of the patients in our cohort. Additional Sanger sequencing yielded a second mutation in 17 patients (6.8%), thereby establishing the molecular diagnosis. In total, 38 patients (15.2%) received a molecular diagnosis after analysis using the microarray and additional Sanger sequencing approach. Further genetic analyses after a negative result of the arRP microarray (n = 107) resulted in a molecular diagnosis of arRP (n = 23), autosomal dominant RP (n = 5), X-linked RP (n = 2), and choroideremia (n = 1). The efficacy of the commercially available APEX microarray chips for arRP appears to be low, most likely caused by the limitations of this technique and the genetic and allelic heterogeneity of RP. Diagnostic yields up to 40% have been reported for next-generation sequencing (NGS) techniques that, as expected, thereby outperform targeted APEX analysis.

  9. Four-year placebo-controlled trial of docosahexaenoic acid in X-linked retinitis pigmentosa (DHAX trial): a randomized clinical trial.

    PubMed

    Hoffman, Dennis R; Hughbanks-Wheaton, Dianna K; Pearson, N Shirlene; Fish, Gary E; Spencer, Rand; Takacs, Alison; Klein, Martin; Locke, Kirsten G; Birch, David G

    2014-07-01

    X-linked retinitis pigmentosa is a severe inherited retinal degenerative disease with a frequency of 1 in 100,000 persons. Because no cure is available for this orphan disease and treatment options are limited, slowing of disease progression would be a meaningful outcome. To determine whether high-dose docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid, slows progression of X-linked retinitis pigmentosa measured by cone electroretinography (ERG). A 4-year, single-site, randomized, placebo-controlled, double-masked phase 2 clinical trial at a research center specializing in medical retina. Seventy-eight male patients diagnosed as having X-linked retinitis pigmentosa were randomized to DHA or placebo. Data were omitted for 2 patients with non-X-linked retinitis pigmentosa and 16 patients who were unable to follow protocol during the first year. The remaining participants were tested annually and composed a modified intent-to-treat cohort (DHA group, n = 33; placebo group, n = 27). All participants received a multivitamin and were randomly assigned to oral DHA (30 mg/kg/d) or placebo. The primary outcome was the rate of loss of cone ERG function. Secondary outcomes were rod and maximal ERG amplitudes and cone ERG implicit times. Capsule counts and red blood cell DHA levels were assessed to monitor adherence. Average (6-month to 4-year) red blood cell DHA levels were 4-fold higher in the DHA group than in the placebo group (P < .001). There was no difference between the DHA and placebo groups in the rate of cone ERG functional loss (0.028 vs 0.022 log µV/y, respectively; P = .30). No group differences were evident for change in rod ERG (P = .27), maximal ERG (P = .65), or cone implicit time (no change over 4 years). The rate of cone loss (ie, event rate) was markedly reduced compared with rates in previous studies. No severe treatment-emergent adverse events were found. Long-term DHA supplementation was not effective in slowing the

  10. Blood flow and anatomical MRI in a mouse model of retinitis pigmentosa.

    PubMed

    Muir, Eric R; De La Garza, Bryan; Duong, Timothy Q

    2013-01-01

    This study tested the sensitivity of an arterial spin labeling MRI method to image changes in retinal and choroidal blood flow (BF) and anatomical thickness of the retina in the rd10 mouse model of retinitis pigmentosa. High-resolution (42 × 42 μm) MRI was performed on rd10 mice and age-matched controls at 25, 35, and 60 days of age (n = 6 each group) on a 7-T scanner. Anatomical MRI was acquired, and quantitative BF was imaged using arterial spin labeling MRI with a separate cardiac labeling coil. Histology was obtained to confirm thickness changes in the retina. In control mice, the retinal and choroidal vascular layers were quantitatively resolved. In rd10 mice, retinal BF decreased progressively over time, while choroidal BF was unchanged. The rd10 retina became progressively thinner at later time points compared with age-matched controls by anatomical MRI and histology (P < 0.01). BF and anatomical MRI were capable of detecting decreased BF and thickness in the rd10 mouse retina. Because BF is tightly coupled to metabolic function, BF MRI has the potential to noninvasively assess retinal diseases in which metabolism and function are perturbed and to evaluate novel treatments, complementing existing retinal imaging techniques. Copyright © 2012 Wiley Periodicals, Inc.

  11. Involvement of LCA5 in Leber congenital amaurosis and retinitis pigmentosa in the Spanish population.

    PubMed

    Corton, Marta; Avila-Fernandez, Almudena; Vallespín, Elena; López-Molina, María Isabel; Almoguera, Berta; Martín-Garrido, Esther; Tatu, Sorina D; Khan, M Imran; Blanco-Kelly, Fiona; Riveiro-Alvarez, Rosa; Brión, María; García-Sandoval, Blanca; Cremers, Frans P M; Carracedo, Angel; Ayuso, Carmen

    2014-01-01

    We aimed to identify novel genetic defects in the LCA5 gene underlying Leber congenital amaurosis (LCA) in the Spanish population and to describe the associated phenotype. Case series. A cohort of 217 unrelated Spanish families affected by autosomal recessive or isolated retinal dystrophy, that is, 79 families with LCA and 138 families with early-onset retinitis pigmentosa (EORP). A total of 100 healthy, unrelated Spanish individuals were screened as controls. High-resolution homozygosity mapping was performed in 44 patients with LCA using genome-wide single nucleotide polymorphism (SNP) microarrays. Direct sequencing of the LCA5 gene was performed in 5 patients who showed homozygous regions at chromosome 6 and in 173 unrelated individuals with LCA or EORP. The ophthalmic history of 8 patients carrying LCA5 mutations was reviewed and additional examinations were performed, including electroretinography (ERG), optical coherence tomography (OCT), and fundus photography. Single nucleotide polymorphism genotyping, identity-by-descent (IBD) regions, LCA5 mutations, best-corrected visual acuity, visual field assessments, fundus appearance, ERG, and OCT findings. Four novel and 2 previously reported LCA5 mutations have been identified in 6 unrelated families with LCA by homozygosity mapping or Sanger sequencing. Thus, LCA5 mutations have a frequency of 7.6% in the Spanish population. However, no LCA5 mutations were found in 138 patients with EORP. Although most of the identified LCA5 mutations led to a truncated protein, a likely pathogenic missense variant was identified for the first time as a cause of LCA, segregating in 2 families. We also have characterized a novel splicing site mutation at the RNA level, demonstrating that the mutant LCA5 transcript was absent in a patient. All patients carrying LCA5 mutations presented nystagmus, night blindness, and progressive loss of visual acuity and visual field leading to blindness toward the third decade of life. Fundoscopy

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

    SciTech Connect

    Kajiwara, K.; Berson, E.L.; Dryja, T.P. )

    1994-06-10

    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 ROM 1 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.

  13. A Case of Unilateral Retinitis Pigmentosa Associated with Full Thickness Macular Hole

    PubMed Central

    Enani, Lama; Kozak, Igor; Abdelkader, Ehab

    2017-01-01

    A 44-year-old Saudi female presented with poor right eye vision for 3 years. Visual acuity (VA) was 20/400 in the right eye and 20/20 in the left eye. Examination and imaging showed all the typical features of retinitis pigmentosa in the right eye associated with full thickness macular hole (FTMH) and an essentially normal left eye. The case underwent pars plana vitrectomy with internal limiting membrane peeling and gas tamponade that resulted in anatomical closure of the FTMH, but VA remained the same. PMID:28936059

  14. Autofluorescence imaging and spectral-domain optical coherence tomography in incomplete congenital stationary night blindness and comparison with retinitis pigmentosa.

    PubMed

    Chen, Royce W S; Greenberg, Jonathan P; Lazow, Margot A; Ramachandran, Rithu; Lima, Luiz H; Hwang, John C; Schubert, Carl; Braunstein, Alexandra; Allikmets, Rando; Tsang, Stephen H

    2012-01-01

    To test the hypothesis that the evaluation of retinal structure can have diagnostic value in differentiating between incomplete congenital stationary night blindness (CSNB2) and retinitis pigmentosa (RP). To compare retinal thickness differences between patients with CSNB2 and myopic controls. Prospective cross-sectional study. Ten eyes of 5 patients diagnosed with CSNB2 (4 X-linked recessive, 1 autosomal recessive) and 6 eyes of 3 patients with RP (2 autosomal dominant, 1 autosomal recessive) were evaluated with spectral-domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF). Diagnoses of CSNB2 and RP were confirmed by full-field electroretinography (ERG). Manual segmentation of retinal layers, aided by a computer program, was performed by 2 professional segmenters on SD OCT images of all CSNB2 patients and 4 age-similar, normal myopic controls. Seven patients were screened for mutations with congenital stationary night blindness and RP genotyping arrays. Patients with CSNB2 had specific findings on SD OCT and FAF that were distinct from those found in RP. CSNB2 patients showed qualitatively normal SD OCT results with preserved photoreceptor inner segment/outer segment junction, whereas this junction was lost in RP patients. In addition, CSNB2 patients had normal FAF images, whereas patients with RP demonstrated a ring of increased autofluorescence around the macula. On SD OCT segmentation, the inner and outer retinal layers of both X-linked recessive and autosomal recessive CSNB2 patients were thinner compared with those of normal myopic controls, with means generally outside of normal 95% confidence intervals. The only layers that demonstrated similar thickness between CSNB2 patients and the controls were the retinal nerve fiber layer and, temporal to the fovea, the combined outer segment layer and retinal pigment epithelium. A proband and his 2 affected brothers from a family segregating X-linked recessive CSNB2 had a mutation, p.R614X

  15. Autofluorescence Imaging and Spectral-Domain Optical Coherence Tomography in Incomplete Congenital Stationary Night Blindness and Comparison with Retinitis Pigmentosa

    PubMed Central

    CHEN, ROYCE W. S.; GREENBERG, JONATHAN P.; LAZOW, MARGOT A.; RAMACHANDRAN, RITHU; LIMA, LUIZ H.; HWANG, JOHN C.; SCHUBERT, CARL; BRAUNSTEIN, ALEXANDRA; ALLIKMETS, RANDO; TSANG, STEPHEN H.

    2015-01-01

    PURPOSE To test the hypothesis that the evaluation of retinal structure can have diagnostic value in differentiating between incomplete congenital stationary night blindness (CSNB2) and retinitis pigmentosa (RP). To compare retinal thickness differences between patients with CSNB2 and myopic controls. DESIGN Prospective cross-sectional study. METHODS Ten eyes of 5 patients diagnosed with CSNB2 (4 X-linked recessive, 1 autosomal recessive) and 6 eyes of 3 patients with RP (2 autosomal dominant, 1 autosomal recessive) were evaluated with spectral-domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF). Diagnoses of CSNB2 and RP were confirmed by full-field electroretinography (ERG). Manual segmentation of retinal layers, aided by a computer program, was performed by 2 professional segmenters on SD OCT images of all CSNB2 patients and 4 age-similar, normal myopic controls. Seven patients were screened for mutations with congenital stationary night blindness and RP genotyping arrays. RESULTS Patients with CSNB2 had specific findings on SD OCT and FAF that were distinct from those found in RP. CSNB2 patients showed qualitatively normal SD OCT results with preserved photoreceptor inner segment/outer segment junction, whereas this junction was lost in RP patients. In addition, CSNB2 patients had normal FAF images, whereas patients with RP demonstrated a ring of increased autofluorescence around the macula. On SD OCT segmentation, the inner and outer retinal layers of both X-linked recessive and autosomal recessive CSNB2 patients were thinner compared with those of normal myopic controls, with means generally outside of normal 95% confidence intervals. The only layers that demonstrated similar thickness between CSNB2 patients and the controls were the retinal nerve fiber layer and, temporal to the fovea, the combined outer segment layer and retinal pigment epithelium. A proband and his 2 affected brothers from a family segregating X-linked recessive

  16. Inverse pattern of photoreceptor abnormalities in retinitis pigmentosa and cone-rod dystrophy.

    PubMed

    Yokochi, Midori; Li, Danjie; Horiguchi, Masayuki; Kishi, Shoji

    2012-12-01

    To determine the characteristics of the photoreceptor abnormalities in retinitis pigmentosa (RP) and cone-rod dystrophy (CRD). We evaluated the photoreceptor abnormalities using spectral-domain optical coherence tomography (SD-OCT) in 28 patients with RP and 17 patients with CRD. The OCT images and full-field electroretinograms were obtained from 21 eyes in normal subjects who were age-matched to patients with RP and CRD and served as controls. Eyes with RP and CRD had markedly decreased rod responses (6.5 and 57.5 % of normal value), maximal responses (9.6 and 51.6 %), cone (16.5 and 25.8 %), and 30-Hz flicker responses (17.8 and 30.1 % of normal value), and their P values were smaller than 0.0003. On comparison of ERG data between RP and CRD, they had statistically significant differences in rod responses (P < 0.0003) and maximal responses (P < 0.0003). However, there were no statistical differences in cone response and a weak difference in 30-Hz flicker responses (P < 0.017). The best-corrected visual acuity was -0.03 ± 0.09 (logMAR, mean ± standard deviation [SD]) in eyes with RP, but 0.57 ± 0.54 in eyes with CRD. SD-OCT showed that eyes with RP had an intact reflective line at the junction between the photoreceptor inner and outer segment (IS/OS) at the fovea, while eyes with CRD had no IS/OS. The extent of the central visual field was correlated with the IS/OS length at the macula in eyes with RP. The distribution patterns of the IS/OS line help to differentiate between RP and CRD.

  17. Identification of novel mutations in X-linked retinitis pigmentosa families and implications for diagnostic testing

    PubMed Central

    Glaus, Esther; Lorenz, Birgit; Netzer, Christian; Li, Yün; Schambeck, Maria; Wittmer, Mariana; Feil, Silke; Kirschner-Schwabe, Renate; Rosenberg, Thomas; Cremers, Frans P.M.; Bergen, Arthur A.B.; Barthelmes, Daniel; Baraki, Husnia; Schmid, Fabian; Tanner, Gaby; Fleischhauer, Johannes; Orth, Ulrike; Becker, Christian; Wegscheider, Erika; Nürnberg, Gudrun; Nürnberg, Peter; Bolz, Hanno Jörn; Gal, Andreas; Berger, Wolfgang

    2008-01-01

    Purpose The goal of this study was to identify mutations in X-chromosomal genes associated with retinitis pigmentosa (RP) in patients from Germany, The Netherlands, Denmark, and Switzerland. Methods In addition to all coding exons of RP2, exons 1 through 15, 9a, ORF15, 15a and 15b of RPGR were screened for mutations. PCR products were amplified from genomic DNA extracted from blood samples and analyzed by direct sequencing. In one family with apparently dominant inheritance of RP, linkage analysis identified an interval on the X chromosome containing RPGR, and mutation screening revealed a pathogenic variant in this gene. Patients of this family were examined clinically and by X-inactivation studies. Results This study included 141 RP families with possible X-chromosomal inheritance. In total, we identified 46 families with pathogenic sequence alterations in RPGR and RP2, of which 17 mutations have not been described previously. Two of the novel mutations represent the most 3’-terminal pathogenic sequence variants in RPGR and RP2 reported to date. In exon ORF15 of RPGR, we found eight novel and 14 known mutations. All lead to a disruption of open reading frame. Of the families with suggested X-chromosomal inheritance, 35% showed mutations in ORF15. In addition, we found five novel mutations in other exons of RPGR and four in RP2. Deletions in ORF15 of RPGR were identified in three families in which female carriers showed variable manifestation of the phenotype. Furthermore, an ORF15 mutation was found in an RP patient who additionally carries a 6.4 kbp deletion downstream of the coding region of exon ORF15. We did not identify mutations in 39 sporadic male cases from Switzerland. Conclusions RPGR mutations were confirmed to be the most frequent cause of RP in families with an X-chromosomal inheritance pattern. We propose a screening strategy to provide molecular diagnostics in these families. PMID:18552978

  18. Genetic highthroughput screening in retinitis pigmentosa based on high resolution melting (HRM) analysis.

    PubMed

    Anasagasti, Ander; Barandika, Olatz; Irigoyen, Cristina; Benitez, Bruno A; Cooper, Breanna; Cruchaga, Carlos; López de Munain, Adolfo; Ruiz-Ederra, Javier

    2013-10-24

    Retinitis Pigmentosa (RP) involves a group of genetically determined retinal diseases caused by a large number of mutations that result in rod photoreceptor cell death followed by gradual death of cone cells. Most cases of RP are monogenic, with more than 80 associated genes identified so far. The high number of genes and variants involved in RP, among other factors, is making the molecular characterization of RP a real challenge for many patients. Although HRM has been used for the analysis of isolated variants or single RP genes, as far as we are concerned, this is the first study that uses HRM analysis for a high-throughput screening of several RP genes. Our main goal was to test the suitability of HRM analysis as a genetic screening technique in RP, and to compare its performance with two of the most widely used NGS platforms, Illumina and PGM-Ion Torrent technologies. RP patients (n=96) were clinically diagnosed at the Ophthalmology Department of Donostia University Hospital, Spain. We analyzed a total of 16 RP genes that meet the following inclusion criteria: 1) size: genes with transcripts of less than 4 kb; 2) number of exons: genes with up to 22 exons; and 3) prevalence: genes reported to account for, at least, 0.4 % of total RP cases worldwide. For comparison purposes, RHO gene was also sequenced with Illumina (GAII; Illumina), Ion semiconductor technologies (PGM; Life Technologies) and Sanger sequencing (ABI 3130xl platform; Applied Biosystems). Detected variants were confirmed in all cases by Sanger sequencing and tested for co-segregation in the family of affected probands. We identified a total of 65 genetic variants, 15 of which (23%) were novel, in 49 out of 96 patients. Among them, 14 (4 novel) are probable disease-causing genetic variants in 7 RP genes, affecting 15 patients. Our HRM analysis-based study, proved to be a cost-effective and rapid method that provides an accurate identification of genetic RP variants. This approach is effective for

  19. Compound heterozygosity of two novel truncation mutations in RP1 causing autosomal recessive retinitis pigmentosa.

    PubMed

    Chen, Li Jia; Lai, Timothy Y Y; Tam, Pancy O S; Chiang, Sylvia W Y; Zhang, Xin; Lam, Shi; Lai, Ricky Y K; Lam, Dennis S C; Pang, Chi Pui

    2010-04-01

    Purpose. To evaluate the phenotypic effects of two novel frameshift mutations in the RP1 gene in a Chinese pedigree of autosomal recessive retinitis pigmentosa (ARRP). Methods. Family members of a proband with ARRP were screened for RP1, RHO, NR2E3, and NRL mutations by direct sequencing. Detected RP1 mutations were genotyped in 225 control subjects. Since one family member with the RP1 deletion mutation in exon 2 was found to have age-related macular degeneration (AMD) but not RP, exons 2 and 3 of RP1 were screened in 120 patients with exudative AMD. Major AMD-associated SNPs in the HTRA1 and CFH genes were also investigated. Results. Two novel frameshift mutations in RP1, c.5_6delGT and c.4941_4942insT, were identified in the pedigree. They were absent in 225 control subjects. Family members who were compound heterozygous for the nonsense mutations had early-onset and severe RP, whereas those with only one mutation did not have RP. No mutations in RHO, NR2E3, and NRL were identified in the pedigree. Subject I:2 with AMD carried both at-risk genotypes at HTRA1 rs11200638 and CFH rs800292. No mutation in RP1 exons 2 and 3 was identified in 120 AMD patients. Conclusions. This report is the first to associate ARRP with compound heterozygous nonsense mutations in RP1. Identification of the nonsense-mediated mRNA decay (NMD)-sensitive mutation c.5_6delGT provided further genetic evidence that haploinsufficiency of RP1 is not responsible for RP. The authors propose four classes of truncation mutations in the RP1 gene with different effects on the etiology of RP.

  20. A population-based epidemiological and genetic study of X-linked retinitis pigmentosa.

    PubMed

    Prokisch, Holger; Hartig, Monika; Hellinger, Rosa; Meitinger, Thomas; Rosenberg, Thomas

    2007-09-01

    To perform a nation-wide elucidation of the prevalence and the mutation spectrum in X-linked retinitis pigmentosa (XLRP), and to make genotype-phenotype comparisons. The study comprised 96 affected males and 149 female carriers from 42 families representing all identified XLRP individuals in the Danish population (5.4 million inhabitants). RPGR and RP2 were screened for mutations in 34 families, the medical files of the patients were scrutinized, and phenotype data were extracted. The prevalence of affected males was estimated to be 1:26,200 and 1:18,000 of female carriers. A rough estimate, however, indicates that the real prevalence of affected males was approximately 1:15,000. The cumulated life risk of development of XLRP in carriers was strongly age dependent and included one third of the carriers older than 60 years. Molecular analysis of RP2 and RPGR uncovered 28 different mutations in 33 of 34 index cases analyzed. Twelve patients carried a mutation in RP2, 12 in exons 1 to 14, and 9 in open reading frame (ORF) 15 of RPGR. Males with RP2 mutations tended to have higher degrees of myopia, lower visual acuities, and more preserved visual fields than did males with RPGR mutations at the same age. No significant differences in phenotype were found in age of onset and type of mutation in either RP2 or RPGR. A very high mutation detection rate in familial cases makes genetic testing a valuable clinical tool for genetic counseling and prenatal testing. The proportion of RP2-mediated XLRP in the Danish population is higher and the proportion of RPGR-ORF15 is lower than reported in other studies. Thus, strategies for diagnostic procedures should take into account the population-specific mutation spectrum.

  1. Proinsulin slows retinal degeneration and vision loss in the P23H rat model of retinitis pigmentosa.

    PubMed

    Fernández-Sánchez, Laura; Lax, Pedro; Isiegas, Carolina; Ayuso, Eduard; Ruiz, José M; de la Villa, Pedro; Bosch, Fatima; de la Rosa, Enrique J; Cuenca, Nicolás

    2012-12-01

    Proinsulin has been characterized as a neuroprotective molecule. In this work we assess the therapeutic potential of proinsulin on photoreceptor degeneration, synaptic connectivity, and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa (RP). P23H homozygous rats received an intramuscular injection of an adeno-associated viral vector serotype 1 (AAV1) expressing human proinsulin (hPi+) or AAV1-null vector (hPi-) at P20. Levels of hPi in serum were determined by enzyme-linked immunosorbent assay (ELISA), and visual function was evaluated by electroretinographic (ERG) recording at P30, P60, P90, and P120. Preservation of retinal structure was assessed by immunohistochemistry at P120. Human proinsulin was detected in serum from rats injected with hPi+ at all times tested, with average hPi levels ranging from 1.1 nM (P30) to 1.4 nM (P120). ERG recordings showed an amelioration of vision loss in hPi+ animals. The scotopic b-waves were significantly higher in hPi+ animals than in control rats at P90 and P120. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. hPi+ animals had 48.7% more photoreceptors than control animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were preserved in hPi+ P23H rats. Furthermore, in hPi+ rat retinas the number of rod bipolar cell bodies was greater than in control rats. Our data demonstrate that hPi expression preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in the P23H rat. These data strongly support the further development of proinsulin-based therapy to counteract retinitis pigmentosa.

  2. Proinsulin Slows Retinal Degeneration and Vision Loss in the P23H Rat Model of Retinitis Pigmentosa

    PubMed Central

    Fernández-Sánchez, Laura; Lax, Pedro; Isiegas, Carolina; Ayuso, Eduard; Ruiz, José M.; de la Villa, Pedro; Bosch, Fatima; de la Rosa, Enrique J.

    2012-01-01

    Abstract Proinsulin has been characterized as a neuroprotective molecule. In this work we assess the therapeutic potential of proinsulin on photoreceptor degeneration, synaptic connectivity, and functional activity of the retina in the transgenic P23H rat, an animal model of autosomal dominant retinitis pigmentosa (RP). P23H homozygous rats received an intramuscular injection of an adeno-associated viral vector serotype 1 (AAV1) expressing human proinsulin (hPi+) or AAV1-null vector (hPi−) at P20. Levels of hPi in serum were determined by enzyme-linked immunosorbent assay (ELISA), and visual function was evaluated by electroretinographic (ERG) recording at P30, P60, P90, and P120. Preservation of retinal structure was assessed by immunohistochemistry at P120. Human proinsulin was detected in serum from rats injected with hPi+ at all times tested, with average hPi levels ranging from 1.1 nM (P30) to 1.4 nM (P120). ERG recordings showed an amelioration of vision loss in hPi+ animals. The scotopic b-waves were significantly higher in hPi+ animals than in control rats at P90 and P120. This attenuation of visual deterioration correlated with a delay in photoreceptor degeneration and the preservation of retinal cytoarchitecture. hPi+ animals had 48.7% more photoreceptors than control animals. Presynaptic and postsynaptic elements, as well as the synaptic contacts between photoreceptors and bipolar or horizontal cells, were preserved in hPi+ P23H rats. Furthermore, in hPi+ rat retinas the number of rod bipolar cell bodies was greater than in control rats. Our data demonstrate that hPi expression preserves cone and rod structure and function, together with their contacts with postsynaptic neurons, in the P23H rat. These data strongly support the further development of proinsulin-based therapy to counteract retinitis pigmentosa. PMID:23017108

  3. Environmental Enrichment Extends Photoreceptor Survival and Visual Function in a Mouse Model of Retinitis Pigmentosa

    PubMed Central

    Barone, Ilaria; Novelli, Elena; Piano, Ilaria; Gargini, Claudia; Strettoi, Enrica

    2012-01-01

    Slow, progressive rod degeneration followed by cone death leading to blindness is the pathological signature of all forms of human retinitis pigmentosa (RP). Therapeutic schemes based on intraocular delivery of neuroprotective agents prolong the lifetime of photoreceptors and have reached the stage of clinical trial. The success of these approaches depends upon optimization of chronic supply and appropriate combination of factors. Environmental enrichment (EE), a novel neuroprotective strategy based on enhanced motor, sensory and social stimulation, has already been shown to exert beneficial effects in animal models of various disorders of the CNS, including Alzheimer and Huntington disease. Here we report the results of prolonged exposure of rd10 mice, a mutant strain undergoing progressive photoreceptor degeneration mimicking human RP, to such an enriched environment from birth. By means of microscopy of retinal tissue, electrophysiological recordings, visual behaviour assessment and molecular analysis, we show that EE considerably preserves retinal morphology and physiology as well as visual perception over time in rd10 mutant mice. We find that protective effects of EE are accompanied by increased expression of retinal mRNAs for CNTF and mTOR, both factors known as instrumental to photoreceptor survival. Compared to other rescue approaches used in similar animal models, EE is highly effective, minimally invasive and results into a long-lasting retinal protection. These results open novel perspectives of research pointing to environmental strategies as useful tools to extend photoreceptor survival. PMID:23209820

  4. Autosomal dominant retinitis pigmentosa with apparent incomplete penetrance: a clinical, electrophysiological, psychophysical, and molecular genetic study.

    PubMed Central

    Moore, A T; Fitzke, F; Jay, M; Arden, G B; Inglehearn, C F; Keen, T J; Bhattacharya, S S; Bird, A C

    1993-01-01

    Twenty five symptomatic individuals and six asymptomatic obligate gene carriers from four families with autosomal dominant retinitis pigmentosa (adRP) showing apparent incomplete penetrance have been studied. Symptomatic individuals from three families showed early onset of night blindness, non-recordable rod electroretinograms, and marked elevation of both rod and cone thresholds in all subjects tested. In the fourth family, there was more variation in the age of onset of night blindness and some symptomatic individuals showed well preserved rod and cone function in some retinal areas. All asymptomatic individuals tested had evidence of mild abnormalities of rod and cone function, indicating that these families show marked variation in expressivity rather than true non-penetrance of the adRP gene. No mutations of the rhodopsin or RDS genes were found in these families and the precise genetic mutation(s) remain to be identified. PMID:8025041

  5. Fine genetic mapping of a gene for autosomal recessive retinitis pigmentosa on chromosome 6p21

    SciTech Connect

    Shugart, Yin Y.; Banerjee, P.; Knowles, J.A.

    1995-08-01

    The inherited retinal degenerations known as retinitis pigmentosa (RP) can be caused by mutations at many different loci and can be inherited as an autosomal recessive, autosomal dominant, or X-linked recessive trait. Two forms of autosomal recessive (arRP) have been reported to cosegregate with mutations in the rhodopsin gene and the beta-subunit of rod phosphodiesterase on chromosome 4p. Genetic linkage has been reported on chromosomes 6p and 1q. In a large Dominican family, we reported an arRp gene near the region of the peripherin/RDS gene. Four recombinations were detected between the disease locus and an intragenic marker derived from peripherin/RDS. 26 refs., 2 figs., 1 tab.

  6. Mutation analysis in 129 genes associated with other forms of retinal dystrophy in 157 families with retinitis pigmentosa based on exome sequencing

    PubMed Central

    Xu, Yan; Guan, Liping; Xiao, Xueshan; Zhang, Jianguo; Li, Shiqiang; Jiang, Hui; Jia, Xiaoyun; Yang, Jianhua; Guo, Xiangming; Yin, Ye; Wang, Jun

    2015-01-01

    Purpose Mutations in 60 known genes were previously identified by exome sequencing in 79 of 157 families with retinitis pigmentosa (RP). This study analyzed variants in 129 genes associated with other forms of hereditary retinal dystrophy in the same cohort. Methods Apart from the 73 genes previously analyzed, a further 129 genes responsible for other forms of hereditary retinal dystrophy were selected based on RetNet. Variants in the 129 genes determined by whole exome sequencing were selected and filtered by bioinformatics analysis. Candidate variants were confirmed by Sanger sequencing and validated by analysis of available family members and controls. Results A total of 90 candidate variants were present in the 129 genes. Sanger sequencing confirmed 83 of the 90 variants. Analysis of family members and controls excluded 76 of these 83 variants. The remaining seven variants were considered to be potential pathogenic mutations; these were c.899A>G, c.1814C>G, and c.2107C>T in BBS2; c.1073C>T and c.1669C>T in INPP5E; and c.3582C>G and c.5704–5C>G in CACNA1F. Six of these seven mutations were novel. The mutations were detected in five unrelated patients without a family history, including three patients with homozygous or compound heterozygous mutations in BBS2 and INPP5E, and two patients with hemizygous mutations in CACNA1F. None of the patients had mutations in the genes associated with autosome dominant retinal dystrophy. Conclusions Only a small portion of patients with RP, about 3% (5/157), had causative mutations in the 129 genes associated with other forms of hereditary retinal dystrophy. PMID:25999675

  7. Response to Drs. Shastry and Trese: Phenotype-genotype correlations in X-linked retinitis pigmentosa

    SciTech Connect

    Kaplan, J.; Munnich, A.

    1996-11-11

    Shastry and Trese recently reported on a large kindred with X-linked retinitis pigmentosa (XLRP) characterized by a loss of central vision and preserved peripheral function. In their report, the disease had an early onset with severe myopia and a loss of central vision, while night blindness occurred later. Genetic analysis suggested that the disease was linked to the RP2 locus, and the authors raised the question of whether other cases linked to RP2 could display a similar loss of central vision. Three years ago, we reported on 4 large XLRP pedigrees with a very early onset with severe myopia and early loss of visual acuity, while in 5 other families the disease started later with night blindness. We showed that the first clinical form was linked to RP2, while the second was linked to RP3. Thus, the major difference between the two forms concerns the initial symptom, information which can be obtained from the parents and patients after careful questioning. By contrast, in adult life, no difference in either severity of disease or aspect of the fundus was observed in our series, regardless of the clinical subtype of XLRP. Some months later, Jacobson et al. reported on a pedigree with an RP2 genotype, and their data support the notion that in XLRP of RP2 type 1, cone dysfunction takes place first, and as the disease advances both rods and cones are affected. We were very happy, therefore, to read that the study of Shastry and Trese fully confirmed our previous findings. 3 refs.

  8. Autosomal dominant retinitis pigmentosa: no evidence for nonallelic genetic heterogeneity on 3q.

    PubMed Central

    Kumar-Singh, R; Wang, H; Humphries, P; Farrar, G J

    1993-01-01

    Since the initial report of linkage of autosomal dominant retinitis pigmentosa (adRP) to the long arm of chromosome 3, several mutations in the gene encoding rhodopsin, which also maps to 3q, have been reported in adRP pedigrees. However, there has been some discussion as to the possibility of a second adRP locus on 3q. This suggestion has important diagnostic and research implications and must raise doubts about the usefulness of linked markers for reliable diagnosis of RP patients. In order to address this issue we have performed an admixture test (A-test) on 10 D3S47-linked adRP pedigrees and have found a likelihood ratio of heterogeneity versus homogeneity of 4.90. We performed a second A-test, combining the data from all families with known rhodopsin mutations. In this test we obtained a reduced likelihood ratio of heterogeneity versus homogeneity, of 1.0. On the basis of these statistical analyses we have found no significant support for two adRP loci on chromosome 3q. Furthermore, using 40 CEPH families, we have localized the rhodopsin gene to the D3S47-D3S20 interval, with a maximum lod score (Zm) of 20 and have found that the order qter-D3S47-rhodopsin-D3S20-cen is significantly more likely than any other order. In addition, we have mapped (Zm = 30) the microsatellite marker D3S621 relative to other loci in this region of the genome. PMID:8430695

  9. Retrospective Analysis of Structural Disease Progression in Retinitis Pigmentosa Utilizing Multimodal Imaging.

    PubMed

    Cabral, Thiago; Sengillo, Jesse D; Duong, Jimmy K; Justus, Sally; Boudreault, Katherine; Schuerch, Kaspar; Belfort, Rubens; Mahajan, Vinit B; Sparrow, Janet R; Tsang, Stephen H

    2017-09-04

    In this report, we assess the natural progression rate of retinitis pigmentosa (RP) over an average of three years using spectral-domain optical coherence tomography (SD-OCT) and short wavelength fundus autofluorescence (SW-AF). Measurement of the ellipsoid zone (EZ) line width and hyperautofluorescent ring diameters was performed in 81 patients with RP in a retrospective, longitudinal fashion. Rate of structural disease progression, symmetry between eyes, and test-retest variability were quantified. We observed on average, EZ-line widths decreased by 140 µm (5.2%, p < 0.001) per year, and average horizontal and vertical hyperautofluorescent ring diameters decreased by 149 µm (3.6%, p < 0.001) and 120 µm (3.9%, p < 0.001) per year, respectively. The 95th percentile of this cohort had differences in progression slopes between eyes that were less than 154 µm, 118 µm, and 132 µm for EZ-line width and horizontal and vertical ring diameters, respectively. For all measures except horizontal ring diameter, progression rates were significantly slower at end-stage disease. From our data, we observed a statistically significant progression rate in EZ line width and SW-AF ring diameters over time, verifying the utility of these measurements for disease monitoring purposes. Additionally, calculated differences in progression slopes between eyes may prove useful for investigators evaluating the efficacy of unilateral treatments for RP in clinical trials.

  10. Impact of Retinitis Pigmentosa on Quality of Life, Mental Health, and Employment Among Young Adults.

    PubMed

    Chaumet-Riffaud, Anne Elisabeth; Chaumet-Riffaud, Philippe; Cariou, Anaelle; Devisme, Céline; Audo, Isabelle; Sahel, José-Alain; Mohand-Said, Saddek

    2017-05-01

    To determine the relationship between visual function and quality of life, education, mental health, and employment among young adults with retinitis pigmentosa (RP). Cross-sectional study. Inclusion of 148 patients (mean age 38.2 ± 7.1 years) diagnosed with RP, living in France. Quality of life was assessed using the National Eye Institute Visual Function Questionnaire (VFQ-25), mental state with the Hospital and Anxiety and Depression Scale (HADS), and employment with a specifically designed questionnaire. Limited visual impairment was noted in 22.3%, low vision in 29.7%, and legal blindness in 48.0%. There was a correlation between quality-of-life scores and residual visual field (P < .0001). Mental health scores were suggestive of anxiety in 36.5% and depression in 15.5%. The rates did not increase with disability level (P = .738, P = .134). The percentage of subjects with higher education did not significantly decrease with disability level (P = .113). The employment rate did not significantly decrease with disability level (P = .276). It was lower in subjects reporting depression (P = .0414). Self-rated impact of RP on employment increased with disability level (P = .02642). Our results differ from previous results showing lower education rates and employment rates in young adults with RP. Further research is warranted focusing on the impact of mental health, education, workplace conditions, and employment aids on employment rate vs age- and education-matched normally sighted controls to guide visual disability strategies in RP. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Autosomal dominant retinitis pigmentosa: No evidence for nonallelic genetic heterogeneity on 3q

    SciTech Connect

    Kumar-Singh, R.; He Wang; Humphries, P.; Farrar, G.J. )

    1993-02-01

    Since the initial report of linkage of autosomal dominant retinitis pigmentosa (adRP) to the long arm of chromosome 3, several mutations in the gene encoding rhodopsin, which also maps to 3q, have been reported in adRP pedigrees. However, there has been some discussion as to the possibility of a second adRP locus on 3q. This suggestion has important diagnostic and research implications and must raise doubts about the usefulness of linked markers for reliable diagnosis of RP patients. In order to address this issue the authors have performed an admixture test (A-test) on 10 D3S47-linked adRP pedigrees and have found a likelihood ratio of heterogeneity versus homogeneity of 4.90. They performed a second A-test, combining the data from all families with known rhodopsin mutations. In this test they obtained a reduced likelihood ratio of heterogeneity versus homogeneity, of 1.0. On the basis of these statistical analyses they have found no significant support for two adRP loci on chromosome 3q. Furthermore, using 40 CEPH families, they have localized the rhodopsin gene to the D3S47-D3S20 interval, with a maximum lod score (Z[sub m]) of 20 and have found that the order qter-D3S47-rhodopsin-D3S20-cen is significantly more likely than any other order. In addition, they have mapped (Z[sub m] = 30) the microsatellite marker D3S621 relative to other loci in this region of the genome. 27 refs., 3 figs., 3 tabs.

  12. Whole Exome Sequencing of a Dominant Retinitis Pigmentosa Family Identifies a Novel Deletion in PRPF31

    PubMed Central

    Villanueva, Adda; Willer, Jason R.; Bryois, Julien; Dermitzakis, Emmanouil T.; Katsanis, Nicholas; Davis, Erica E.

    2014-01-01

    Purpose. Mutations at some retinitis pigmentosa (RP) loci are associated with variable penetrance and expressivity, exacerbating diagnostic challenges. The purpose of this study was to dissect the genetic underpinnings of nonsyndromic RP with variable age of onset in a large Mexican family. Methods. We ascertained members of a large, multigenerational pedigree using a complete ophthalmic examination. We performed whole exome sequencing on two affected first cousins, an obligate carrier, and a married-in spouse. Confirmatory sequencing of candidate variants was performed in the entire pedigree, as well as genotyping and mRNA studies to investigate expression changes in the causal locus. Results. We identified a 14–base pair (bp) deletion in PRPF31, a gene implicated previously in autosomal dominant (ad) RP. The mutation segregated with the phenotype of all 10 affected females, but also was present in six asymptomatics (two females and four males). Studies in patient cells showed that the penetrance/expressivity of the PRPF31 deletion allele was concordant with the expression levels of wild-type message. However, neither the known PRPF31 modulators nor cis-eQTLs within 1 Mb of the locus could account for the variable expression of message or the clinical phenotype. Conclusions. We have identified a novel 14-bp deletion in PRPF31 as the genetic driver of adRP in a large Mexican family that exhibits nonpenetrance and variable expressivity, known properties of this locus. However, our studies intimate the presence of additional loci that can modify PRPF31 expression. PMID:24595387

  13. Insights from retinitis pigmentosa into the roles of isocitrate dehydrogenases in the Krebs cycle.

    PubMed

    Hartong, Dyonne T; Dange, Mayura; McGee, Terri L; Berson, Eliot L; Dryja, Thaddeus P; Colman, Roberta F

    2008-10-01

    Here we describe two families with retinitis pigmentosa, a hereditary neurodegeneration of rod and cone photoreceptors in the retina. Affected family members were homozygous for loss-of-function mutations in IDH3B, encoding the beta-subunit of NAD-specific isocitrate dehydrogenase (NAD-IDH, or IDH3), which is believed to catalyze the oxidation of isocitrate to alpha-ketoglutarate in the citric acid cycle. Cells from affected individuals had a substantial reduction of NAD-IDH activity, with about a 300-fold increase in the K(m) for NAD. NADP-specific isocitrate dehydrogenase (NADP-IDH, or IDH2), an enzyme that catalyzes the same reaction, was normal in affected individuals, and they had no health problems associated with the enzyme deficiency except for retinitis pigmentosa. These findings support the hypothesis that mitochondrial NADP-IDH, rather than NAD-IDH, serves as the main catalyst for this reaction in the citric acid cycle outside the retina, and that the retina has a particular requirement for NAD-IDH.

  14. Genetic analysis of a kindred with X-linked mental handicap and retinitis pigmentosa

    SciTech Connect

    Aldred, M.A.; Dry, K.L.; Hardwick, L.J.; Teague, P.W.; Lester, D.H.; Brown, J.; Spowart, G.; Carothers, A.D.; Wright, A.F.; Knight-Jones, E.B.

    1994-11-01

    A kindred is described in which X-linked nonspecific mental handicap segregates together with retinitis pigmentosa. Carrier females are mentally normal but may show signs of the X-linked retinitis pigmentosa carrier state and become symptomatic in their later years. Analysis of polymorphic DNA markers at nine loci on the short arm of the X chromosome shows that no crossing-over occurs between the disease and Xp11 markers DXS255, TIMP, DXS426, MAOA, and DXS228. The 90% confidence limits show that the locus is in the Xp21-q21 region. Haplotype analysis is consistent with the causal gene being located proximal to the Xp21 loci DXS538 and 5{prime}-dystrophin on the short arm of the X chromosome. The posterior probability of linkage to the RP2 region of the X chromosome short arm (Xp11.4-p11.23) is .727, suggesting the possibility of a contiguous-gene-deletion syndrome. No cytogenetic abnormality has been identified. 33 refs., 2 figs., 2 tabs.

  15. Small molecules targeting glycogen synthase kinase 3 as potential drug candidates for the treatment of retinitis pigmentosa.

    PubMed

    Marchena, Miguel; Villarejo-Zori, Beatriz; Zaldivar-Diez, Josefa; Palomo, Valle; Gil, Carmen; Hernández-Sánchez, Catalina; Martínez, Ana; de la Rosa, Enrique J

    2017-12-01

    Retinitis pigmentosa (RP) is an inherited retinal dystrophy that courses with progressive degeneration of retinal tissue and loss of vision. Currently, RP is an unpreventable, incurable condition. We propose glycogen synthase kinase 3 (GSK-3) inhibitors as potential leads for retinal cell neuroprotection, since the retina is also a part of the central nervous system and GSK-3 inhibitors are potent neuroprotectant agents. Using a chemical genetic approach, diverse small molecules with different potency and binding mode to GSK-3 have been used to validate and confirm GSK-3 as a pharmacological target for RP. Moreover, this medicinal chemistry approach has provided new leads for the future disease-modifying treatment of RP.

  16. AAV delivery of wild-type rhodopsin preserves retinal function in a mouse model of autosomal dominant retinitis pigmentosa.

    PubMed

    Mao, Haoyu; James, Thomas; Schwein, Alison; Shabashvili, Arseniy E; Hauswirth, William W; Gorbatyuk, Marina S; Lewin, Alfred S

    2011-05-01

    Autosomal dominant retinitis pigmentosa (ADRP) is frequently caused by mutations in RHO, the gene for rod photoreceptor opsin. Earlier, a study on mice carrying mutated rhodopsin transgenes on either RHO + / +  or RHO + /- backgrounds suggested that the amount of wild-type rhodopsin affected survival of photoreceptors. Therefore, we treated P23H RHO transgenic mice with adeno-associated virus serotype 5 (AAV5) expressing a cDNA clone of the rhodopsin gene (RHO301) that expressed normal opsin from the mouse opsin promoter. Analysis of the electroretinogram (ERG) demonstrated that increased expression of RHO301 slowed the rate of retinal degeneration in P23H mice: at 6 months, a-wave amplitudes were increased by 100% and b-wave amplitudes by 79%. In contrast, nontransgenic mice injected with AAV5 RHO301 demonstrated a decrease in the ERG, confirming the damaging effect of rhodopsin overproduction in normal photoreceptors. In P23H mice, the increase in the ERG amplitudes was correlated with improvement of retinal structure: the thickness of the outer nuclear layer in RHO301-treated eyes was increased by 80% compared with control eyes. These findings suggest that the wild-type RHO gene can be delivered to rescue retinal degeneration in mice carrying a RHO mutation and that increased production of normal rhodopsin can suppress the effect of the mutated protein. These findings make it possible to treat ADRP caused by different mutations of RHO with the expression of wild-type RHO.

  17. Mutations in the X-linked retinitis pigmentosa genes RPGR and RP2 found in 8.5% of families with a provisional diagnosis of autosomal dominant retinitis pigmentosa.

    PubMed

    Churchill, Jennifer D; Bowne, Sara J; Sullivan, Lori S; Lewis, Richard Alan; Wheaton, Dianna K; Birch, David G; Branham, Kari E; Heckenlively, John R; Daiger, Stephen P

    2013-02-19

    We determined the fraction of families in a well-characterized cohort with a provisional diagnosis of autosomal dominant retinitis pigmentosa (adRP) that have disease-causing mutations in the X-linked retinitis pigmentosa GTPase regulator (RPGR) gene or the retinitis pigmentosa 2 (RP2) gene. Families with a provisional clinical diagnosis of adRP, and a pedigree consistent with adRP but no male-to-male transmission were selected from a cohort of 258 families, and tested for mutations in the RPGR and RP2 genes with di-deoxy sequencing. To facilitate testing of RPGR in "adRP" families that had no male members available for testing, the repetitive and purine-rich ORF15 of RPGR was subcloned and sequenced in heterozygous female subjects from 16 unrelated families. Direct sequencing of RPGR and RP2 allowed for identification of a disease-causing mutation in 21 families. Of these "adRP" families 19 had RPGR mutations, and two had RP2 mutations. Subcloning and sequencing of ORF15 of RPGR in female subjects identified one additional RPGR mutation. Of the 22 mutations identified, 15 have been reported previously. These data show that 8.5% (22 in 258) of families thought to have adRP truly have X-linked retinitis pigmentosa (XLRP). These results have substantive implications for calculation of recurrence risk, genetic counseling, and potential treatment options, and illustrate the importance of screening families with a provisional diagnosis of autosomal inheritance and no male-to-male transmission for mutations in X-linked genes. Mutations in RPGR are one of the most common causes of all forms of retinitis pigmentosa.

  18. Whole exome sequencing identifies a novel NRL mutation in a Chinese family with autosomal dominant retinitis pigmentosa

    PubMed Central

    Gao, Meng; Zhang, Su; Liu, Chunjie; Qin, Yayun; Archacki, Stephen; Jin, Ling; Wang, Yong; Liu, Fei; Chen, Jiaxiang; Liu, Ying; Wang, Jiuxiang; Huang, Mi; Liao, Shengjie; Tang, Zhaohui; Guo, An Yuan; Liu, Mugen

    2016-01-01

    Purpose To investigate the genetic basis and its relationship to the clinical manifestations in a four generation Chinese family with autosomal dominant retinitis pigmentosa. Methods Ophthalmologic examinations including fundus photography, fundus autofluorescence imaging, fundus fluorescein angiography, optical coherence tomography, and a best-corrected visual acuity test were performed to define the clinical features of the patients. We extracted the genomic DNA from peripheral blood samples. The proband’s genomic DNA was submitted to the whole exome sequencing. Results Whole exome sequencing and the subsequent data analysis detected six candidate mutations in the proband of this pedigree. The novel c.146 C>T mutation in NRL was found to be the only mutation that co-segregated with the disease in this pedigree. This mutation resulted in a substitution of proline by a leucine at position 49 of NRL protein (p.P49L). Most importantly, the proline residue at position 49 of NRL is highly conserved from zebrafish to humans. The c.146 C>T mutation was not observed in 200 control individuals. What’s more, we performed the luciferase activity assay to prove that this mutation we detected alters the NRL protein function. Conclusions The c.146 C>T mutation in NRL gene causes autosomal dominant retinitis pigmentosa for this family. Our finding not only expands the mutation spectrum of NRL, but also demonstrates that whole-exome sequencing is a powerful strategy to detect causative genes and mutations in RP patients. This technique may provide a precise diagnosis for rare heterogeneous monogenic disorders such as RP. PMID:27081294

  19. Whole exome sequencing identifies a novel NRL mutation in a Chinese family with autosomal dominant retinitis pigmentosa.

    PubMed

    Gao, Meng; Zhang, Su; Liu, Chunjie; Qin, Yayun; Archacki, Stephen; Jin, Ling; Wang, Yong; Liu, Fei; Chen, Jiaxiang; Liu, Ying; Wang, Jiuxiang; Huang, Mi; Liao, Shengjie; Tang, Zhaohui; Guo, An Yuan; Jiang, Fagang; Liu, Mugen

    2016-01-01

    To investigate the genetic basis and its relationship to the clinical manifestations in a four generation Chinese family with autosomal dominant retinitis pigmentosa. Ophthalmologic examinations including fundus photography, fundus autofluorescence imaging, fundus fluorescein angiography, optical coherence tomography, and a best-corrected visual acuity test were performed to define the clinical features of the patients. We extracted the genomic DNA from peripheral blood samples. The proband's genomic DNA was submitted to the whole exome sequencing. Whole exome sequencing and the subsequent data analysis detected six candidate mutations in the proband of this pedigree. The novel c.146 C>T mutation in NRL was found to be the only mutation that co-segregated with the disease in this pedigree. This mutation resulted in a substitution of proline by a leucine at position 49 of NRL protein (p.P49L). Most importantly, the proline residue at position 49 of NRL is highly conserved from zebrafish to humans. The c.146 C>T mutation was not observed in 200 control individuals. What's more, we performed the luciferase activity assay to prove that this mutation we detected alters the NRL protein function. The c.146 C>T mutation in NRL gene causes autosomal dominant retinitis pigmentosa for this family. Our finding not only expands the mutation spectrum of NRL, but also demonstrates that whole-exome sequencing is a powerful strategy to detect causative genes and mutations in RP patients. This technique may provide a precise diagnosis for rare heterogeneous monogenic disorders such as RP.

  20. Melatonin delays photoreceptor degeneration in a mouse model of autosomal recessive retinitis pigmentosa.

    PubMed

    Xu, Xiao-Jian; Wang, Shu-Min; Jin, Ying; Hu, Yun-Tao; Feng, Kang; Ma, Zhi-Zhong

    2017-10-01

    Retinitis pigmentosa (RP) comprises a group of incurable inherited retinal degenerations. Targeting common processes, instead of mutation-specific treatment, has proven to be an innovative strategy to combat debilitating retinal degeneration. Growing evidence indicates that melatonin possesses a potent activity against neurodegenerative disorders by mitigating cell damage associated with apoptosis and inflammation. Given the pleiotropic role of melatonin in central nervous system, the aim of the present study was to investigate whether melatonin would afford protection against retinal degeneration in autosomal recessive RP (arRP). Rd10, a well-characterized murine model of human arRP, received daily intraperitoneal injection of melatonin (15 mg/kg) between postnatal day (P) 13 and P30. Retinas treated with melatonin or vehicle were harvested for analysis at P30 and P45, respectively. The findings showed that melatonin could dampen the photoreceptors death and delay consequent retinal degeneration. We also observed that melatonin weakened the expression of glial fibrillary acidic protein (GFAP) in Müller cells. Additionally, melatonin could alleviate retinal inflammatory response visualized by IBA1 staining, which was further corroborated by downregulation of inflammation-related genes, such as tumor necrosis factor alpha (Tnf-α), chemokine (C-C motif) ligand 2 (Ccl2), and chemokine (C-X-C motif) ligand 10 (Cxcl10). These data revealed that melatonin could ameliorate retinal degeneration through potentially attenuating apoptosis, reactive gliosis, and microglial activation in rd10 mice. Moreover, these results suggest melatonin as a promising agent improving photoreceptors survival in human RP. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Compound heterozygosity for a novel and a recurrent MFRP gene mutation in a family with the nanophthalmos-retinitis pigmentosa complex.

    PubMed

    Zenteno, Juan Carlos; Buentello-Volante, Beatriz; Quiroz-González, Miguel A; Quiroz-Reyes, Miguel A

    2009-09-05

    To report a new familial case of the recently described autosomal recessive syndrome of nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen, which arises from compound heterozygosity for Membrane Frizzled-Related Protein (MFRP) mutations in a sibling pair of Mexican origin. Ophthalmological assessment included slit-lamp and dilated fundus examination, applanation tonometry, fundus photography, A-mode and B-mode ultrasound examination, electroretinogram, fluorescein retinal angiography, optical coherence tomography, and electrooculogram in both affected siblings. Molecular genetic analysis consisted of PCR amplification and direct automated sequence of the complete coding region of the MFRP gene. In addition, allele-specific cloning and sequencing techniques were used to characterize a heterozygous MFRP frameshift mutation. Clinical examination revealed high hyperopia of > +16 diopters while electroretinographic and fluorangiographic studies demonstrated a retinal dystrophy compatible with retinitis pigmentosa. Ultrasound examination showed nanophthalmos (eye axial length <15 mm) and optic disc drusen while optical coherence tomography evidenced cystoid macular edema. Nucleotide sequencing in DNA from both affected siblings disclosed the presence of two MFRP mutations: a novel heterozygous point mutation predicting a nonsense change from tyrosine (TAC) to a stop signal (TAA) at codon 317, and a heterozygous 1 bp deletion in exon 5, predicting a prematurely truncated protein (p.Asn167ThrfsX25). The third known family with the syndrome of nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen is presented. This is the first demonstration of compound heterozygosity for MFRP mutations as the source of the disease. The affected siblings described here are the youngest patients with the disease reported to date and the comparison of their clinical data with previous individuals with this syndrome suggest that some aspects of the phenotype are

  2. Compound heterozygosity for a novel and a recurrent MFRP gene mutation in a family with the nanophthalmos-retinitis pigmentosa complex

    PubMed Central

    Buentello-Volante, Beatriz; Quiroz-González, Miguel A.; Quiroz-Reyes, Miguel A.

    2009-01-01

    Purpose To report a new familial case of the recently described autosomal recessive syndrome of nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen, which arises from compound heterozygosity for Membrane Frizzled-Related Protein (MFRP) mutations in a sibling pair of Mexican origin. Methods Ophthalmological assessment included slit-lamp and dilated fundus examination, applanation tonometry, fundus photography, A-mode and B-mode ultrasound examination, electroretinogram, fluorescein retinal angiography, optical coherence tomography, and electrooculogram in both affected siblings. Molecular genetic analysis consisted of PCR amplification and direct automated sequence of the complete coding region of the MFRP gene. In addition, allele-specific cloning and sequencing techniques were used to characterize a heterozygous MFRP frameshift mutation. Results Clinical examination revealed high hyperopia of > +16 diopters while electroretinographic and fluorangiographic studies demonstrated a retinal dystrophy compatible with retinitis pigmentosa. Ultrasound examination showed nanophthalmos (eye axial length <15 mm) and optic disc drusen while optical coherence tomography evidenced cystoid macular edema. Nucleotide sequencing in DNA from both affected siblings disclosed the presence of two MFRP mutations: a novel heterozygous point mutation predicting a nonsense change from tyrosine (TAC) to a stop signal (TAA) at codon 317, and a heterozygous 1 bp deletion in exon 5, predicting a prematurely truncated protein (p.Asn167ThrfsX25). Discussion The third known family with the syndrome of nanophthalmos-retinitis pigmentosa-foveoschisis-optic disc drusen is presented. This is the first demonstration of compound heterozygosity for MFRP mutations as the source of the disease. The affected siblings described here are the youngest patients with the disease reported to date and the comparison of their clinical data with previous individuals with this syndrome suggest that

  3. Gene therapy rescues photoreceptor blindness in dogs and paves the way for treating human X-linked retinitis pigmentosa.

    PubMed

    Beltran, William A; Cideciyan, Artur V; Lewin, Alfred S; Iwabe, Simone; Khanna, Hemant; Sumaroka, Alexander; Chiodo, Vince A; Fajardo, Diego S; Román, Alejandro J; Deng, Wen-Tao; Swider, Malgorzata; Alemán, Tomas S; Boye, Sanford L; Genini, Sem; Swaroop, Anand; Hauswirth, William W; Jacobson, Samuel G; Aguirre, Gustavo D

    2012-02-07

    Hereditary retinal blindness is caused by mutations in genes expressed in photoreceptors or retinal pigment epithelium. Gene therapy in mouse and dog models of a primary retinal pigment epithelium disease has already been translated to human clinical trials with encouraging results. Treatment for common primary photoreceptor blindness, however, has not yet moved from proof of concept to the clinic. We evaluated gene augmentation therapy in two blinding canine photoreceptor diseases that model the common X-linked form of retinitis pigmentosa caused by mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, which encodes a photoreceptor ciliary protein, and provide evidence that the therapy is effective. After subretinal injections of adeno-associated virus-2/5-vectored human RPGR with human IRBP or GRK1 promoters, in vivo imaging showed preserved photoreceptor nuclei and inner/outer segments that were limited to treated areas. Both rod and cone photoreceptor function were greater in treated (three of four) than in control eyes. Histopathology indicated normal photoreceptor structure and reversal of opsin mislocalization in treated areas expressing human RPGR protein in rods and cones. Postreceptoral remodeling was also corrected: there was reversal of bipolar cell dendrite retraction evident with bipolar cell markers and preservation of outer plexiform layer thickness. Efficacy of gene therapy in these large animal models of X-linked retinitis pigmentosa provides a path for translation to human treatment.

  4. Loss of HCN1 enhances disease progression in mouse models of CNG channel-linked retinitis pigmentosa and achromatopsia.

    PubMed

    Schön, Christian; Asteriti, Sabrina; Koch, Susanne; Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Tanimoto, Naoyuki; Herms, Jochen; Seeliger, Mathias W; Cangiano, Lorenzo; Biel, Martin; Michalakis, Stylianos

    2016-03-15

    Most inherited blinding diseases are characterized by compromised retinal function and progressive degeneration of photoreceptors. However, the factors that affect the life span of photoreceptors in such degenerative retinal diseases are rather poorly understood. Here, we explore the role of hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) in this context. HCN1 is known to adjust retinal function under mesopic conditions, and although it is expressed at high levels in rod and cone photoreceptor inner segments, no association with any retinal disorder has yet been found. We investigated the effects of an additional genetic deletion of HCN1 on the function and survival of photoreceptors in a mouse model of CNGB1-linked retinitis pigmentosa (RP). We found that the absence of HCN1 in Cngb1 knockout (KO) mice exacerbated photoreceptor degeneration. The deleterious effect was reduced by expression of HCN1 using a viral vector. Moreover, pharmacological inhibition of HCN1 also enhanced rod degeneration in Cngb1 KO mice. Patch-clamp recordings revealed that the membrane potentials of Cngb1 KO and Cngb1/Hcn1 double-KO rods were both significantly depolarized. We also found evidence for altered calcium homeostasis and increased activation of the protease calpain in Cngb1/Hcn1 double-KO mice. Finally, the deletion of HCN1 also exacerbated degeneration of cone photoreceptors in a mouse model of CNGA3-linked achromatopsia. Our results identify HCN1 as a major modifier of photoreceptor degeneration and suggest that pharmacological inhibition of HCN channels may enhance disease progression in RP and achromatopsia patients.

  5. Retinitis pigmentosa-associated cystoid macular oedema: pathogenesis and avenues of intervention

    PubMed Central

    Strong, S; Liew, G; Michaelides, M

    2017-01-01

    Hereditary retinal diseases are now the leading cause of blindness certification in the working age population (age 16–64 years) in England and Wales, of which retinitis pigmentosa (RP) is the most common disorder. RP may be complicated by cystoid macular oedema (CMO), causing a reduction of central vision. The underlying pathogenesis of RP-associated CMO (RP-CMO) remains uncertain, however, several mechanisms have been proposed, including: (1) breakdown of the blood-retinal barrier, (2) failure (or dysfunction) of the pumping mechanism in the retinal pigment epithelial, (3) Müller cell oedema and dysfunction, (4) antiretinal antibodies and (5) vitreous traction. There are limited data on efficacy of treatments for RP-CMO. Treatments attempted to date include oral and topical carbonic anhydrase inhibitors, oral, topical, intravitreal and periocular steroids, topical non-steroidal anti-inflammatory medications, photocoagulation, vitrectomy with internal limiting membrane peel, oral lutein and intravitreal antivascular endothelial growth factor injections. This review summarises the evidence supporting these treatment modalities. Successful management of RP-CMO should aim to improve both quality and quantity of vision in the short term and may also slow central vision loss over time. PMID:27913439

  6. A dominant mutation in hexokinase 1 (HK1) causes retinitis pigmentosa.

    PubMed

    Sullivan, Lori S; Koboldt, Daniel C; Bowne, Sara J; Lang, Steven; Blanton, Susan H; Cadena, Elizabeth; Avery, Cheryl E; Lewis, Richard A; Webb-Jones, Kaylie; Wheaton, Dianna H; Birch, David G; Coussa, Razck; Ren, Huanan; Lopez, Irma; Chakarova, Christina; Koenekoop, Robert K; Garcia, Charles A; Fulton, Robert S; Wilson, Richard K; Weinstock, George M; Daiger, Stephen P

    2014-09-04

    To identify the cause of retinitis pigmentosa (RP) in UTAD003, a large, six-generation Louisiana family with autosomal dominant retinitis pigmentosa (adRP). A series of strategies, including candidate gene screening, linkage exclusion, genome-wide linkage mapping, and whole-exome next-generation sequencing, was used to identify a mutation in a novel disease gene on chromosome 10q22.1. Probands from an additional 404 retinal degeneration families were subsequently screened for mutations in this gene. Exome sequencing in UTAD003 led to identification of a single, novel coding variant (c.2539G>A, p.Glu847Lys) in hexokinase 1 (HK1) present in all affected individuals and absent from normal controls. One affected family member carries two copies of the mutation and has an unusually severe form of disease, consistent with homozygosity for this mutation. Screening of additional adRP probands identified four other families (American, Canadian, and Sicilian) with the same mutation and a similar range of phenotypes. The families share a rare 450-kilobase haplotype containing the mutation, suggesting a founder mutation among otherwise unrelated families. We identified an HK1 mutation in five adRP families. Hexokinase 1 catalyzes phosphorylation of glucose to glucose-6-phosphate. HK1 is expressed in retina, with two abundant isoforms expressed at similar levels. The Glu847Lys mutation is located at a highly conserved position in the protein, outside the catalytic domains. We hypothesize that the effect of this mutation is limited to the retina, as no systemic abnormalities in glycolysis were detected. Prevalence of the HK1 mutation in our cohort of RP families is 1%. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  7. A Dominant Mutation in Hexokinase 1 (HK1) Causes Retinitis Pigmentosa

    PubMed Central

    Sullivan, Lori S.; Koboldt, Daniel C.; Bowne, Sara J.; Lang, Steven; Blanton, Susan H.; Cadena, Elizabeth; Avery, Cheryl E.; Lewis, Richard A.; Webb-Jones, Kaylie; Wheaton, Dianna H.; Birch, David G.; Coussa, Razck; Ren, Huanan; Lopez, Irma; Chakarova, Christina; Koenekoop, Robert K.; Garcia, Charles A.; Fulton, Robert S.; Wilson, Richard K.; Weinstock, George M.; Daiger, Stephen P.

    2014-01-01

    Purpose. To identify the cause of retinitis pigmentosa (RP) in UTAD003, a large, six-generation Louisiana family with autosomal dominant retinitis pigmentosa (adRP). Methods. A series of strategies, including candidate gene screening, linkage exclusion, genome-wide linkage mapping, and whole-exome next-generation sequencing, was used to identify a mutation in a novel disease gene on chromosome 10q22.1. Probands from an additional 404 retinal degeneration families were subsequently screened for mutations in this gene. Results. Exome sequencing in UTAD003 led to identification of a single, novel coding variant (c.2539G>A, p.Glu847Lys) in hexokinase 1 (HK1) present in all affected individuals and absent from normal controls. One affected family member carries two copies of the mutation and has an unusually severe form of disease, consistent with homozygosity for this mutation. Screening of additional adRP probands identified four other families (American, Canadian, and Sicilian) with the same mutation and a similar range of phenotypes. The families share a rare 450-kilobase haplotype containing the mutation, suggesting a founder mutation among otherwise unrelated families. Conclusions. We identified an HK1 mutation in five adRP families. Hexokinase 1 catalyzes phosphorylation of glucose to glucose-6-phosphate. HK1 is expressed in retina, with two abundant isoforms expressed at similar levels. The Glu847Lys mutation is located at a highly conserved position in the protein, outside the catalytic domains. We hypothesize that the effect of this mutation is limited to the retina, as no systemic abnormalities in glycolysis were detected. Prevalence of the HK1 mutation in our cohort of RP families is 1%. PMID:25190649

  8. A Survey of Photopsias in Self-reported Retinitis Pigmentosa: Location of Photopsias is related to Disease Severity

    PubMed Central

    Bittner, Ava K.; Diener-West, Marie; Dagnelie, Gislin

    2009-01-01

    Purpose To characterize photopsias or light shows in patients self-reporting retinitis pigmentosa (RP), and determine associations between their location and patient-reported visual function. Methods 127 self-reported RP patients with varying levels of vision completed an anonymous survey on an internet website. Results 118 (93%) of respondents reported photopsias. The majority (60%) who experience photopsias have them daily, 48% already had them prior to being diagnosed with RP, and 69% report interference with vision. The proportions noting photopsias mostly peripherally versus centrally were: 53% of those reading normal or small print versus 35% requiring magnification (odds ratio[OR]:2.3; 95% CI:1.0–5.5; p=0.05); 61% of current drivers versus 41% who stopped or never drove (OR:2.6; 95% CI:1.0–6.7; p=0.04); and 54% of individuals who easily navigate or have only minor difficulty in unfamiliar areas versus 29% of those with great difficulty or needing assistance with mobility (OR:3.0; 95% CI:1.2–6.7; p=0.02). Conclusions Contrary to common belief that photopsias are associated with end-stage retinal degeneration, they are also commonly reported in earlier stages. The location of photopsias appears to be related to residual photoreceptor function assessed by self-reported