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Sample records for amaurosis fugax

  1. Leber Congenital Amaurosis

    Science.gov (United States)

    ... Congenital Amaurosis Macular Degeneration Retinitis Pigmentosa Stargardt Disease Usher Syndrome Other Retinal Diseases Glossary News & Research News & ... affected by retinitis pigmentosa, age-related macular degeneration, Usher syndrome and the entire spectrum of retinal diseases. ...

  2. Linear interictal pain in Epicrania Fugax: a reply

    OpenAIRE

    Wang, Yu; Pan, Qing-Qing; Lu, Ya-Nan; Tian, Miao-Miao; Wang, Xian-Hong

    2015-01-01

    This is a reply to the comments on our article “Linear headache: a recurrent unilateral head pain circumscribed in a line-shaped area” published in JHP 2014 Jun 26; 15:45. In the comments, the authors raise a question whether the linear headache (LH) we reported be a linear interictal pain in epicranial fugax (EF), based on a case they reported. We think that the LH is not a linear interictal pain in EF based on our observations and considerations.

  3. Molecular genetics of Leber congenital amaurosis.

    NARCIS (Netherlands)

    Cremers, F.P.M.; Hurk, J.A.J.M. van den; Hollander, A.I. den

    2002-01-01

    Leber congenital amaurosis (LCA) is the most common inherited cause of blindness in childhood and is characterised by a severe retinal dystrophy before the age of one year. Six genes have been identified that together account for approximately half of all LCA patients. These genes are expressed pref

  4. Pathophysilogical Mechanism and Treatment Strategies for Leber Congenital Amaurosis

    OpenAIRE

    Fu, Yingbin; Zhang, Tao

    2014-01-01

    Mutations in retinoid isomerase, RPE65, or lecithin-retinol acyltransferase (LRAT) disrupt 11-cis-retinal recycling and cause Leber congenital amaurosis (LCA), the most severe retinal dystrophy in early childhood. We used Lrat−/−, a murine model for LCA, to investigate the mechanism of rapid cone degeneration. We found that mislocalized M-opsin was degraded whereas mislocalized S-opsin accumulated in Lrat−/− cones before the onset of massive ventral/central cone degeneration. Since the ventra...

  5. Retinal Dehydrogenase 12 (RDH12) Mutations in Leber Congenital Amaurosis

    OpenAIRE

    Perrault, Isabelle; Hanein, Sylvain; Gerber, Sylvie; Barbet, Fabienne; Ducroq, Dominique; Dollfus, Helene; Hamel, Christian,; Dufier, Jean-Louis; Munnich, Arnold; Kaplan, Josseline; Rozet, Jean-Michel

    2004-01-01

    Leber congenital amaurosis (LCA), the most early-onset and severe form of all inherited retinal dystrophies, is responsible for congenital blindness. Ten LCA genes have been mapped, and seven of these have been identified. Because some of these genes are involved in the visual cycle, we regarded the retinal pigment epithelium and photoreceptor-specific retinal dehydrogenase (RDH) genes as candidate genes in LCA. Studying a series of 110 unrelated patients with LCA, we found mutations in the p...

  6. Sequential treatment for proctalgia fugax: Mid-term follow-up Tratamiento secuencial para la proctalgia fugaz: Resultados a medio plazo

    OpenAIRE

    J. A. Gracia Solanas; J. M. Ramírez Rodríguez; M. Elía Guedea; V. Aguilella Diago; M. Martínez Díez

    2005-01-01

    Introduction: proctalgia fugax (PF) is a benign, self-limiting disease characterized by episodes of intense anorectal pain at frequent intervals in the absence of organic proctological disease. Even though PF was described more than a century ago, its etiology remains unclear. Currently there is no information available. Few papers quoting many ways of management have been published. The aim of this study was to investigate patients complaining of this condition and to treat them with sequent...

  7. Pathophysilogical mechanism and treatment strategies for Leber congenital amaurosis.

    Science.gov (United States)

    Fu, Yingbin; Zhang, Tao

    2014-01-01

    Mutations in retinoid isomerase, RPE65, or lecithin-retinol acyltransferase (LRAT) disrupt 11-cis-retinal recycling and cause Leber congenital amaurosis (LCA), the most severe retinal dystrophy in early childhood. We used Lrat (-/-), a murine model for LCA, to investigate the mechanism of rapid cone degeneration. We found that mislocalized M-opsin was degraded whereas mislocalized S-opsin accumulated in Lrat (-/-) cones before the onset of massive ventral/central cone degeneration. Since the ventral and central retina expresses higher levels of S-opsin than the dorsal retina in mice, our results may explain why ventral and central cones degenerate more rapidly than dorsal cones in Rpe65 (-/-) and Lrat (-/-) LCA models. In addition, human blue opsin and mouse S-opsin, but not mouse M-opsin or human red/green opsins, aggregated to form cytoplasmic inclusions in transfected cells, which may explain why blue cone function is lost earlier than red/green-cone function in LCA patients. The aggregation of short-wavelength opsins likely caused rapid cone degenerations through an ER stress pathway as demonstrated in both the Lrat (-/-) retina and transfected cells. Based on this mechanism, we designed a new therapy of LCA by reducing ER stress. We found that systemic injection of an ER chemical chaperone, tauroursodeoxycholic acid (TUDCA), is effective in reducing ER stress, preventing apoptosis, and preserving cones in Lrat (-/-) mice. PMID:24664772

  8. Characterization of Leber Congenital Amaurosis-associated NMNAT1 Mutants.

    Science.gov (United States)

    Sasaki, Yo; Margolin, Zachary; Borgo, Benjamin; Havranek, James J; Milbrandt, Jeffrey

    2015-07-10

    Leber congenital amaurosis 9 (LCA9) is an autosomal recessive retinal degeneration condition caused by mutations in the NAD(+) biosynthetic enzyme NMNAT1. This condition leads to early blindness but no other consistent deficits have been reported in patients with NMNAT1 mutations despite its central role in metabolism and ubiquitous expression. To study how these mutations affect NMNAT1 function and ultimately lead to the retinal degeneration phenotype, we performed detailed analysis of LCA-associated NMNAT1 mutants, including the expression, nuclear localization, enzymatic activity, secondary structure, oligomerization, and promotion of axonal and cellular integrity in response to injury. In many assays, most mutants produced results similar to wild type NMNAT1. Indeed, NAD(+) synthetic activity is unlikely to be a primary mechanism underlying retinal degeneration as most LCA-associated NMNAT1 mutants had normal enzymatic activity. In contrast, the secondary structure of many NMNAT1 mutants was relatively less stable as they lost enzymatic activity after heat shock, whereas wild type NMNAT1 retains significant activity after this stress. These results suggest that LCA-associated NMNAT1 mutants are more vulnerable to stressful conditions that lead to protein unfolding, a potential contributor to the retinal degeneration observed in this syndrome. PMID:26018082

  9. Pupillometric analysis for assessment of gene therapy in Leber Congenital Amaurosis patients

    OpenAIRE

    Melillo Paolo; Pecchia Leandro; Testa Francesco; Rossi Settimio; Bennett Jean; Simonelli Francesca

    2012-01-01

    Abstract Background Objective techniques to assess the amelioration of vision in patients with impaired visual function are needed to standardize efficacy assessment in gene therapy trials for ocular diseases. Pupillometry has been investigated in several diseases in order to provide objective information about the visual reflex pathway and has been adopted to quantify visual impairment in patients with Leber Congenital Amaurosis (LCA). In this paper, we describe detailed methods of pupillome...

  10. Cone opsin determines the time course of cone photoreceptor degeneration in Leber congenital amaurosis

    OpenAIRE

    Zhang, Tao; Zhang, Ning; Baehr, Wolfgang; Fu, Yingbin

    2011-01-01

    Mutations in RPE65 or lecithin-retinol acyltransferase (LRAT) disrupt 11-cis-retinal recycling and cause Leber congenital amaurosis (LCA), the most severe retinal dystrophy in early childhood. We used Lrat−/−, a murine model for LCA, to investigate the mechanism of rapid cone degeneration. Although both M and S cone opsins mistrafficked as reported previously, mislocalized M-opsin was degraded whereas mislocalized S-opsin accumulated in Lrat−/− cones before the onset of massive ventral/centra...

  11. Exome sequencing identifies NMNAT1 mutations as a cause of Leber congenital amaurosis.

    Science.gov (United States)

    Chiang, Pei-Wen; Wang, Juan; Chen, Yang; Fu, Quan; Zhong, Jing; Chen, Yanhua; Yi, Xin; Wu, Renhua; Gan, Haixue; Shi, Yong; Chen, Yanling; Barnett, Christopher; Wheaton, Dianna; Day, Megan; Sutherland, Joanne; Heon, Elise; Weleber, Richard G; Gabriel, Luis Alexandre Rassi; Cong, Peikuan; Chuang, KuangHsiang; Ye, Sheng; Sallum, Juliana Maria Ferraz; Qi, Ming

    2012-09-01

    Leber congenital amaurosis (LCA) is an autosomal recessive retinal dystrophy that manifests with genetic heterogeneity. We sequenced the exome of an individual with LCA and identified nonsense (c.507G>A, p.Trp169*) and missense (c.769G>A, p.Glu257Lys) mutations in NMNAT1, which encodes an enzyme in the nicotinamide adenine dinucleotide (NAD) biosynthesis pathway implicated in protection against axonal degeneration. We also found NMNAT1 mutations in ten other individuals with LCA, all of whom carry the p.Glu257Lys variant. PMID:22842231

  12. Identification of a novel LCA5 mutation in a Pakistani family with Leber congenital amaurosis and cataracts

    OpenAIRE

    Ahmad, Adeel; Daud, Shakeela; Kakar, Naseebullah; Nürnberg, Gudrun; Nürnberg, Peter; Babar, Masroor Ellahi; Thoenes, Michaela; Kubisch, Christian; Ahmad, Jamil; Bolz, Hanno Jörn

    2011-01-01

    Purpose To determine the cause of Leber congenital amaurosis (LCA) and developmental cataracts in a consanguineous Pakistani family. Methods The diagnosis was established in all affected individuals of a Pakistani LCA family by medical history, funduscopy, and standard ERG. We performed genome-wide linkage analysis for mapping the disease locus in this family. Results Congenitally severely reduced visual acuity and nystagmus were reported for all patients who, in the later phase of the diseas...

  13. Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration

    OpenAIRE

    Koenekoop, Robert K; Wang, Hui; Majewski, Jacek; Wang, Xia; Lopez, Irma; Ren, Huanan; Chen, Yiyun; Li, Yumei; Fishman, Gerald A.; Genead, Mohammed; Schwartzentruber, Jeremy; Solanki, Naimesh; Traboulsi, Elias I.; Cheng, Jingliang; Logan, Clare V.

    2012-01-01

    Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, including the family in which LCA was originally linked to the LCA9 locus. Notably, all individuals with NMNAT1 mutations also have macular colobomas, which are severe degenerative e...

  14. Pupillometric analysis for assessment of gene therapy in Leber Congenital Amaurosis patients

    Directory of Open Access Journals (Sweden)

    Melillo Paolo

    2012-07-01

    Full Text Available Abstract Background Objective techniques to assess the amelioration of vision in patients with impaired visual function are needed to standardize efficacy assessment in gene therapy trials for ocular diseases. Pupillometry has been investigated in several diseases in order to provide objective information about the visual reflex pathway and has been adopted to quantify visual impairment in patients with Leber Congenital Amaurosis (LCA. In this paper, we describe detailed methods of pupillometric analysis and a case study on three Italian patients affected by Leber Congenital Amaurosis (LCA involved in a gene therapy clinical trial at two follow-up time-points: 1 year and 3 years after therapy administration. Methods Pupillary light reflexes (PLR were measured in patients who had received a unilateral subretinal injection in a clinical gene therapy trial. Pupil images were recorded simultaneously in both eyes with a commercial pupillometer and related software. A program was generated with MATLAB software in order to enable enhanced pupil detection with revision of the acquired images (correcting aberrations due to the inability of these severely visually impaired patients to fixate, and computation of the pupillometric parameters for each stimulus. Pupil detection was performed through Hough Transform and a non-parametric paired statistical test was adopted for comparison. Results The developed program provided correct pupil detection also for frames in which the pupil is not totally visible. Moreover, it provided an automatic computation of the pupillometric parameters for each stimulus and enabled semi-automatic revision of computerized detection, eliminating the need for the user to manually check frame by frame. With reference to the case study, the amplitude of pupillary constriction and the constriction velocity were increased in the right (treated eye compared to the left (untreated eye at both follow-up time-points, showing stability of

  15. Cone opsin determines the time course of cone photoreceptor degeneration in Leber congenital amaurosis.

    Science.gov (United States)

    Zhang, Tao; Zhang, Ning; Baehr, Wolfgang; Fu, Yingbin

    2011-05-24

    Mutations in RPE65 or lecithin-retinol acyltransferase (LRAT) disrupt 11-cis-retinal recycling and cause Leber congenital amaurosis (LCA), the most severe retinal dystrophy in early childhood. We used Lrat(-)(/-), a murine model for LCA, to investigate the mechanism of rapid cone degeneration. Although both M and S cone opsins mistrafficked as reported previously, mislocalized M-opsin was degraded whereas mislocalized S-opsin accumulated in Lrat(-)(/-) cones before the onset of massive ventral/central cone degeneration. As the ventral and central retina express higher levels of S-opsin than the dorsal retina in mice, our results may explain why ventral and central cones degenerate more rapidly than dorsal cones in Rpe65(-)(/-) and Lrat(-)(/-) LCA models. In addition, human blue opsin and mouse S-opsin, but not mouse M-opsin or human red/green opsins, aggregated to form cytoplasmic inclusions in transfected cells, which may explain why blue cone function is lost earlier than red/green-cone function in patients with LCA. The aggregation of short-wavelength opsins likely caused rapid cone degenerations through an endoplasmic reticulum stress pathway, as demonstrated in both the Lrat(-)(/-) retina and transfected cells. Replacing rhodopsin with S-opsin in Lrat(-)(/-) rods resulted in mislocalization and aggregation of S-opsin in the inner segment and the synaptic region of rods, ER stress, and dramatically accelerated rod degeneration. Our results demonstrate that cone opsins play a major role in determining the degeneration rate of photoreceptors in LCA. PMID:21555576

  16. Sequential treatment for proctalgia fugax: Mid-term follow-up Tratamiento secuencial para la proctalgia fugaz: Resultados a medio plazo

    Directory of Open Access Journals (Sweden)

    J. A. Gracia Solanas

    2005-07-01

    Full Text Available Introduction: proctalgia fugax (PF is a benign, self-limiting disease characterized by episodes of intense anorectal pain at frequent intervals in the absence of organic proctological disease. Even though PF was described more than a century ago, its etiology remains unclear. Currently there is no information available. Few papers quoting many ways of management have been published. The aim of this study was to investigate patients complaining of this condition and to treat them with sequential therapy. Patients and methods: we devised a descriptive, prospective study of patients complaining of acute perianal pain -duration less than 30 minutes- without organic disease or previous perianal surgery since 1996 to 2002 in our Department. We treated these patients using a three-step treatment (1: information, hip bath, benzodiazepines; 2: sublingual nifedipine 10 mg, or topic 0.1% nitroglycerin on demand; 3: internal anal sphincterotomy if hypertrophy of the internal anal sphincter was demonstrated by anal ultrasonography and no improvement was confirmed with the previous steps of treatment. We defined remarkable improvement as a decrease in the number of episodes by half or in pain intensity by 50%. Results: Fifteen patients with an average follow-up of 4 years. Anal endosonography confirmed a grossly thickened internal anal sphincter (IAS in 5 cases. After the first step of treatment 7 patients improved and 1 patient was cured; after the second step of treatment 3 patients improved and 1 was cured; the third step was applied to 3 patients with a thickened IAS; 1 patient improved and 1 patient was cured. Conclusion: a total resolution of PF is not always possible, but we may improve symptoms and their frequency. Almost 50% of patients in our series improved with the first step of treatment; 30% of our patients had IAS hypertrophy. Anal endosonography can help in the diagnosis of organic diseases or IAS hypertrophy, for which we can perform an

  17. Gene Therapy Rescues Cone Structure and Function in the 3-Month-Old rd12 Mouse: A Model for Midcourse RPE65 Leber Congenital Amaurosis

    OpenAIRE

    Li, Xia; Li, Wensheng; Dai, Xufeng; Kong, Fansheng; Zheng, Qinxiang; Zhou, Xiangtian; Lü, Fan; Chang, Bo; Rohrer, Bärbel; Hauswirth, William W; Qu, Jia; Pang, Ji-jing

    2011-01-01

    This study provides the first proof that late adenoassociated virus (AAV)–mediated RPE65 expression is capable of restoring normal structure and function in the remaining cones of the older rd12 mouse, which is an animal model of human Leber congenital amaurosis type 2.

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

    OpenAIRE

    Mackay, Donna S.; Borman, Arundhati Dev; 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

    2013-01-01

    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 autoflu...

  19. Comprehensive genotyping reveals RPE65 as the most frequently mutated gene in Leber congenital amaurosis in Denmark.

    Science.gov (United States)

    Astuti, Galuh D N; Bertelsen, Mette; Preising, Markus N; Ajmal, Muhammad; Lorenz, Birgit; Faradz, Sultana M H; Qamar, Raheel; Collin, Rob W J; Rosenberg, Thomas; Cremers, Frans P M

    2016-07-01

    Leber congenital amaurosis (LCA) represents the most severe form of inherited retinal dystrophies with an onset during the first year of life. Currently, 21 genes are known to be associated with LCA and recurrent mutations have been observed in AIPL1, CEP290, CRB1 and GUCY2D. In addition, sequence analysis of LRAT and RPE65 may be important in view of treatments that are emerging for patients carrying variants in these genes. Screening of the aforementioned variants and genes was performed in 64 Danish LCA probands. Upon the identification of heterozygous variants, Sanger sequencing was performed of the relevant genes to identify the second allele. In combination with prior arrayed primer extension analysis, this led to the identification of two variants in 42 of 86 cases (49%). Remarkably, biallelic RPE65 variants were identified in 16% of the cases, and one novel variant, p.(D110G), was found in seven RPE65 alleles. We also collected all previously published RPE65 variants, identified in 914 alleles of 539 patients with LCA or early-onset retinitis pigmentosa, and deposited them in the RPE65 Leiden Open Variation Database (LOVD). The in silico pathogenicity assessment of the missense and noncanonical splice site variants, as well as an analysis of their frequency in ~60 000 control individuals, rendered 864 of the alleles to affect function or probably affect function. This comprehensive database can now be used to select patients eligible for gene augmentation or retinoid supplementation therapies. PMID:26626312

  20. Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration

    Science.gov (United States)

    Koenekoop, Robert K.; Wang, Hui; Majewski, Jacek; Wang, Xia; Lopez, Irma; Ren, Huanan; Chen, Yiyun; Li, Yumei; Fishman, Gerald A.; Genead, Mohammed; Schwartzentruber, Jeremy; Solanki, Naimesh; Traboulsi, Elias I.; Cheng, Jingliang; Logan, Clare V.; McKibbin, Martin; Hayward, Bruce E.; Parry, David A.; Johnson, Colin A.; Nageeb, Mohammed; Poulter, James A.; Mohamed, Moin D.; Jafri, Hussain; Rashid, Yasmin; Taylor, Graham R.; Keser, Vafa; Mardon, Graeme; Xu, Huidan; Inglehearn, Chris F.; Fu, Qing; Toomes, Carmel; Chen, Rui

    2013-01-01

    Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, including the family in which LCA was originally linked to the LCA9 locus. Notably, all individuals with NMNAT1 mutations also have macular colobomas, which are severe degenerative entities of the central retina (fovea) devoid of tissue and photoreceptors. Functional assays of the proteins encoded by the mutant alleles identified in our study showed that the mutations reduce the enzymatic activity of NMNAT1 in NAD biosynthesis and affect protein folding. Of note, recent characterization of the slow Wallerian degeneration (Wlds) mouse model, in which prolonged axonal survival after injury is observed, identified NMNAT1 as a neuroprotective protein when ectopically expressed. Our findings identify a new disease mechanism underlying LCA and provide the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder. PMID:22842230

  1. Mutations in NMNAT1 cause Leber congenital amaurosis and identify a new disease pathway for retinal degeneration.

    Science.gov (United States)

    Koenekoop, Robert K; Wang, Hui; Majewski, Jacek; Wang, Xia; Lopez, Irma; Ren, Huanan; Chen, Yiyun; Li, Yumei; Fishman, Gerald A; Genead, Mohammed; Schwartzentruber, Jeremy; Solanki, Naimesh; Traboulsi, Elias I; Cheng, Jingliang; Logan, Clare V; McKibbin, Martin; Hayward, Bruce E; Parry, David A; Johnson, Colin A; Nageeb, Mohammed; Poulter, James A; Mohamed, Moin D; Jafri, Hussain; Rashid, Yasmin; Taylor, Graham R; Keser, Vafa; Mardon, Graeme; Xu, Huidan; Inglehearn, Chris F; Fu, Qing; Toomes, Carmel; Chen, Rui

    2012-09-01

    Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, including the family in which LCA was originally linked to the LCA9 locus. Notably, all individuals with NMNAT1 mutations also have macular colobomas, which are severe degenerative entities of the central retina (fovea) devoid of tissue and photoreceptors. Functional assays of the proteins encoded by the mutant alleles identified in our study showed that the mutations reduce the enzymatic activity of NMNAT1 in NAD biosynthesis and affect protein folding. Of note, recent characterization of the slow Wallerian degeneration (Wld(s)) mouse model, in which prolonged axonal survival after injury is observed, identified NMNAT1 as a neuroprotective protein when ectopically expressed. Our findings identify a new disease mechanism underlying LCA and provide the first link between endogenous NMNAT1 dysfunction and a human nervous system disorder. PMID:22842230

  2. Natural History of Cone Disease in the Murine Model of Leber Congenital Amaurosis Due to CEP290 Mutation: Determining the Timing and Expectation of Therapy

    OpenAIRE

    Boye, Shannon E.; Wei-Chieh Huang; Roman, Alejandro J.; Alexander Sumaroka; Boye, Sanford L.; Ryals, Renee C.; Olivares, Melani B.; Qing Ruan; Tucker, Budd A.; Stone, Edwin M.; Anand Swaroop; Cideciyan, Artur V.; Hauswirth, William W.; Jacobson, Samuel G.

    2014-01-01

    Background Mutations in the CEP290 (cilia-centrosomal protein 290 kDa) gene in Leber congenital amaurosis (LCA) cause early onset visual loss but retained cone photoreceptors in the fovea, which is the potential therapeutic target. A cone-only mouse model carrying a Cep290 gene mutation, rd16;Nrl−/− , was engineered to mimic the human disease. In the current study, we determined the natural history of retinal structure and function in this murine model to permit design of pre-clinical proof-o...

  3. Genetic deletion of S-opsin prevents rapid cone degeneration in a mouse model of Leber congenital amaurosis.

    Science.gov (United States)

    Zhang, Tao; Enemchukwu, Nduka O; Jones, Alex; Wang, Shixian; Dennis, Emily; Watt, Carl B; Pugh, Edward N; Fu, Yingbin

    2015-03-15

    Mutations in RPE65 or lecithin-retinol acyltransferase (LRAT) disrupt 11-cis-retinal synthesis and cause Leber congenital amaurosis (LCA), a severe hereditary blindness occurring in early childhood. The pathology is attributed to a combination of 11-cis-retinal deficiency and photoreceptor degeneration. The mistrafficking of cone membrane-associated proteins including cone opsins (M- and S-opsins), cone transducin (Gαt2), G-protein-coupled receptor kinase 1 (GRK1) and guanylate cyclase 1 (GC1) has been suggested to play a role in cone degeneration. However, their precise role in cone degeneration is unclear. Here we investigated the role of S-opsin (Opn1sw) in cone degeneration in Lrat(-) (/-), a murine model for LCA, by genetic ablation of S-opsin. We show that deletion of just one allele of S-opsin from Lrat(-) (/-) mice is sufficient to prevent the rapid cone degeneration for at least 1 month. Deletion of both alleles of S-opsin prevents cone degeneration for an extended period (at least 12 months). This genetic prevention is accompanied by a reduction of endoplasmic reticulum (ER) stress in Lrat(-) (/-) photoreceptors. Despite cone survival in Opn1sw(-/-)Lrat(-) (/-) mice, cone membrane-associated proteins (e.g. Gαt2, GRK1 and GC1) continue to have trafficking problems. Our results suggest that cone opsins are the 'culprit' linking 11-cis-retinal deficiency to cone degeneration in LCA. This result has important implications for the current gene therapy strategy that emphasizes the need for a combinatorial therapy to both improve vision and slow photoreceptor degeneration. PMID:25416279

  4. Safety in nonhuman primates of ocular AAV2-RPE65, a candidate treatment for blindness in Leber congenital amaurosis.

    Science.gov (United States)

    Jacobson, Samuel G; Boye, Sanford L; Aleman, Tomas S; Conlon, Thomas J; Zeiss, Caroline J; Roman, Alejandro J; Cideciyan, Artur V; Schwartz, Sharon B; Komaromy, Andras M; Doobrajh, Michelle; Cheung, Andy Y; Sumaroka, Alexander; Pearce-Kelling, Susan E; Aguirre, Gustavo D; Kaushal, Shalesh; Maguire, Albert M; Flotte, Terence R; Hauswirth, William W

    2006-08-01

    Leber congenital amaurosis (LCA) is a molecularly heterogeneous disease group that leads to blindness. LCA caused by RPE65 mutations has been studied in animal models and vision has been restored by subretinal delivery of AAV-RPE65 vector. Human ocular gene transfer trials are being considered. Our safety studies of subretinal AAV-2/2.RPE65 in RPE65-mutant dogs showed evidence of modest photoreceptor loss in the injection region in some animals at higher vector doses. We now test the hypothesis that there can be vectorrelated toxicity to the normal monkey, with its human-like retina. Good Laboratory Practice safety studies following single intraocular injections of AAV-2/2.RPE65 in normal cynomolgus monkeys were performed for 1-week and 3-month durations. Systemic toxicity was not identified. Ocular-specific studies included clinical examinations, electroretinography, and retinal histopathology. Signs of ocular inflammation postinjection had almost disappeared by 1 week. At 3 months, electroretinography in vector-injected eyes was no different than in vehicle-injected control eyes or compared with presurgical recordings. Healed sites of retinal perforation from subretinal injections were noted clinically and by histopathology. Foveal architecture in subretinally injected eyes, vector or vehicle, could be abnormal. Morphometry of central retina showed no photoreceptor layer thickness abnormalities occurring in a dose-dependent manner. Vector sequences were present in the injected retina, vitreous, and optic nerve at 1 week but not consistently in the brain. At 3 months, there were no vector sequences in optic nerve and brain. The results allow for consideration of an upper range for no observed adverse effect level in future human trials of subretinal AAV-2/2.RPE65. The potential value of foveal treatment for LCA and other retinal degenerations warrants further research into how to achieve gene transfer without retinal injury from surgical detachment of the retina

  5. Pharmacological and rAAV gene therapy rescue of visual functions in a blind mouse model of Leber congenital amaurosis.

    Directory of Open Access Journals (Sweden)

    2005-11-01

    Full Text Available BACKGROUND: Leber congenital amaurosis (LCA, a heterogeneous early-onset retinal dystrophy, accounts for approximately 15% of inherited congenital blindness. One cause of LCA is loss of the enzyme lecithin:retinol acyl transferase (LRAT, which is required for regeneration of the visual photopigment in the retina. METHODS AND FINDINGS: An animal model of LCA, the Lrat-/- mouse, recapitulates clinical features of the human disease. Here, we report that two interventions--intraocular gene therapy and oral pharmacologic treatment with novel retinoid compounds--each restore retinal function to Lrat-/- mice. Gene therapy using intraocular injection of recombinant adeno-associated virus carrying the Lrat gene successfully restored electroretinographic responses to approximately 50% of wild-type levels (p < 0.05 versus wild-type and knockout controls, and pupillary light responses (PLRs of Lrat-/- mice increased approximately 2.5 log units (p < 0.05. Pharmacological intervention with orally administered pro-drugs 9-cis-retinyl acetate and 9-cis-retinyl succinate (which chemically bypass the LRAT-catalyzed step in chromophore regeneration also caused long-lasting restoration of retinal function in LRAT-deficient mice and increased ERG response from approximately 5% of wild-type levels in Lrat-/- mice to approximately 50% of wild-type levels in treated Lrat-/- mice (p < 0.05 versus wild-type and knockout controls. The interventions produced markedly increased levels of visual pigment from undetectable levels to 600 pmoles per eye in retinoid treated mice, and approximately 1,000-fold improvements in PLR and electroretinogram sensitivity. The techniques were complementary when combined. CONCLUSION: Intraocular gene therapy and pharmacologic bypass provide highly effective and complementary means for restoring retinal function in this animal model of human hereditary blindness. These complementary methods offer hope of developing treatment to restore vision

  6. Omics in Ophthalmology: Advances in Genomics and Precision Medicine for Leber Congenital Amaurosis and Age-Related Macular Degeneration.

    Science.gov (United States)

    den Hollander, Anneke I

    2016-03-01

    The genomic revolution has had a huge impact on our understanding of the genetic defects and disease mechanisms underlying ophthalmic diseases. Two examples are discussed here. The first is Leber congenital amaurosis (LCA), a severe inherited retinal dystrophy leading to severe vision loss in children, and the second is age-related macular degeneration (AMD), the most common cause of vision loss in the elderly. Twenty years ago, the genetic causes of these diseases were unknown. Currently, more than 20 LCA genes have been identified, and genetic testing can now successfully identify the genetic defects in at least 75% of all LCA cases. Gene-specific treatments have entered the clinical trial phase for three LCA genes, and for seven LCA genes gene-specific therapies have been tested in model systems. Age-related macular degeneration is a multifactorial disease caused by a combination of genetic and environmental factors. Currently, more than 40 loci have been identified for AMD, accounting for 15%-65% of the total genetic contribution to AMD. Despite the progress that has been made so far, genetic testing is not yet recommended for AMD, but this may change if we move to clinical trials or treatments that are dependent on an individual's genotype. The identification of serum or plasma biomarkers using other "-omics" technologies may further improve predictive tests and our understanding of the disease mechanisms of AMD. Ultimately, it is anticipated that predictive tests will help to stratify patients for the most suitable therapy, which will enable the development of precision medicine, tailored to individual needs. PMID:27010695

  7. Cerebro-retinal ischemia after bilateral occlusion of internal carotid artery

    International Nuclear Information System (INIS)

    Six patients with occlusion of internal carotid arteries (ICAs) were prospectively followed during a mean period of 14 months. Prior to demonstration of occlusions, four patients suffered a mild stroke, and three isolated transient ischemic attacks (TIAs) or amaurosis fugax. All patients remained alive and with an unchanged functional ability. During follow-up, one patient suffered amaurosis fugax and TIAs followed by a mild stroke, three suffered isolated TIAs or amaurosis fugax, two suffered reversible cerebro-retinal ischemia of more than 24 hours, and one remained symptomfree. In three cases, delayed cerebro-retinal ischemia distal to one of the occluded ICAs was systematically triggered by orthostatic, cardiogenic or iatrogenic hypotension, and resolved after adequate medical treatment or restoration of a functional collateral circulation by endarterectomy of a tightly stenosed ipsilateral external carotid artery (ECA), suggesting hemodynamic phenomena. In three cases, micro-emboli originating from a stump or an ulcerated ipsilateral common carotid artery and migrating through well-developed ECA collateral channels explained delayed episodes of ipsilateral TIAs or amaurosis fugax, which disappeared in two cases after adequate anticoagulant therepy was introduced. Bilateral occlusion of ICA may be a relatively benign condition, if the patients are carefully controlled and treated. (orig.)

  8. Natural History of Cone Disease in the Murine Model of Leber Congenital Amaurosis Due to CEP290 Mutation: Determining the Timing and Expectation of Therapy

    Science.gov (United States)

    Boye, Shannon E.; Huang, Wei-Chieh; Roman, Alejandro J.; Sumaroka, Alexander; Boye, Sanford L.; Ryals, Renee C.; Olivares, Melani B.; Ruan, Qing; Tucker, Budd A.; Stone, Edwin M.; Swaroop, Anand; Cideciyan, Artur V.; Hauswirth, William W.; Jacobson, Samuel G.

    2014-01-01

    Background Mutations in the CEP290 (cilia-centrosomal protein 290 kDa) gene in Leber congenital amaurosis (LCA) cause early onset visual loss but retained cone photoreceptors in the fovea, which is the potential therapeutic target. A cone-only mouse model carrying a Cep290 gene mutation, rd16;Nrl−/−, was engineered to mimic the human disease. In the current study, we determined the natural history of retinal structure and function in this murine model to permit design of pre-clinical proof-of-concept studies and allow progress to be made toward human therapy. Analyses of retinal structure and visual function in CEP290-LCA patients were also performed for comparison with the results in the model. Methods Rd16;Nrl−/− mice were studied in the first 90 days of life with optical coherence tomography (OCT), electroretinography (ERG), retinal histopathology and immunocytochemistry. Structure and function data from a cohort of patients with CEP290-LCA (n = 15; ages 7–48) were compared with those of the model. Results CEP290-LCA patients retain a central island of photoreceptors with normal thickness at the fovea (despite severe visual loss); the extent of this island declined slowly with age. The rd16;Nrl−/− model also showed a relatively slow photoreceptor layer decline in thickness with ∼80% remaining at 3 months. The number of pseudorosettes also became reduced. By comparison to single mutant Nrl−/− mice, UV- and M-cone ERGs of rd16;Nrl−/− were at least 1 log unit reduced at 1 month of age and declined further over the 3 months of monitoring. Expression of GNAT2 and S-opsin also decreased with age. Conclusions The natural history of early loss of photoreceptor function with retained cone cell nuclei is common to both CEP290-LCA patients and the rd16;Nrl−/− murine model. Pre-clinical proof-of-concept studies for uniocular therapies would seem most appropriate to begin with intervention at P35–40 and re-study after one month by assaying

  9. Spontaneous internal carotid dissection in a 38-year-old woman: a case report

    OpenAIRE

    Abed, Kareem; Misra, Amit; Vankawala, Viren

    2015-01-01

    This case report describes a patient found to have amaurosis fugax as a result of non-traumatic internal carotid dissection. Monocular blindness can be due to multiple causes including keratitis, acute glaucoma, vitreous hemorrhage, uveitis, retinal vascular occlusion, retinal detachment, optic neuropathy, trauma, or vascular malformations. In the setting of headache, neck pain, and an otherwise normal ophthalmic examination, this case report highlights the importance of recognizing transient...

  10. Genetics Home Reference: Leber congenital amaurosis

    Science.gov (United States)

    ... types of cells. Cilia are necessary for the perception of several types of sensory input, including vision. ... of the genetic heterogeneity, refinement of the clinical definition, and genotype-phenotype correlations as a strategy for ...

  11. Akut glaukom efter endarterektomi af arteria carotis interna

    DEFF Research Database (Denmark)

    Lindholt, J S; Klaerke, A

    2000-01-01

    A 71 year-old woman had 85% and 60% stenoses of the right and left internal carotid arteries, respectively. Right-sided endarterectomy was performed because of amaurosis fugax. Two days postoperatively, she developed classical symptoms and signs of acute glaucoma. Right-sided acute angle closure...... glaucoma was diagnosed by tonometry and gonioscopy, and treated with laser-iridectomy. The patient was discharged two days later without neurological or ophthalmological deficits. Manifest acute glaucoma postoperatively seems never to have been reported. However, the choroid is not autoregulated, and the...

  12. Choroidal Melanoma Causing Contralateral Amaurosis via Orbital Invasion

    OpenAIRE

    Melis Palamar Onay; Ayşe Yağcı; Taner Akalın

    2011-01-01

    To report a case of tumor invasion into the ipsilateral orbit/optic chiasm and into the contralateral optic nerve. A 51- year-old male who declared removal of his left eye ten years ago elsewhere, attended to our clinic for swelling of the left eyelids and pain. He was ophthalmologically and radiologically evaluated. A hyperpigmented mass was detected at the socket conjunctiva of the patient whose eyelids were swollen and hyperemic. Anterior and posterior segments of the right eye...

  13. Novel compound heterozygous NMNAT1 variants associated with Leber congenital amaurosis

    DEFF Research Database (Denmark)

    Siemiatkowska, Anna M; van den Born, L Ingeborgh; van Genderen, Maria M; Bertelsen, Mette; Zobor, Ditta; Rohrschneider, Klaus; van Huet, Ramon A C; Nurohmah, Siska; Klevering, B Jeroen; Kohl, Susanne; Faradz, Sultana M H; Rosenberg, Thomas; den Hollander, Anneke I; Collin, Rob W J; Cremers, Frans P M

    2014-01-01

    , were screened in 532 additional patients with retinal dystrophies. This cohort encompassed 108 persons with isolated or autosomal recessive cone-rod dystrophy (CRD), 271 with isolated or autosomal recessive retinitis pigmentosa (RP), and 49 with autosomal dominant RP, as well as 104 persons with LCA in...... whom the causative mutation was previously identified. RESULTS: Compound heterozygous alterations were found in six patients with LCA and in one person with early-onset RP. All except one carried the common p.E257K variant on one allele. Macular atrophy was absent in one patient, who carried this......: Although macular atrophy can occur in LCA and CRD, no NMNAT1 mutations were found in the latter cohort. NMNAT1 variants were also not found in a large group of patients with sporadic or autosomal recessive RP. The enrichment of p.E257K ina heterozygous state in patients with LCA versus controls suggests...

  14. A syndrome of congenital retinal dystrophy and saccade palsy--a subset of Leber's amaurosis.

    OpenAIRE

    Moore, A T; Taylor, D. S.

    1984-01-01

    Three children who presented in infancy with a severe visual defect and absent or barely recordable electroretinograms, with relatively well preserved visually evoked cortical potentials, were subsequently found to have vertical and horizontal saccade palsies with head thrusts but relatively good visual acuity. These children, who were clearly different from other infants with congenital retinal dystrophy, were also developmentally delayed and had systemic motor and speech defects, but their ...

  15. fMRI of retina-originated phosphenes experienced by patients with Leber congenital amaurosis.

    Directory of Open Access Journals (Sweden)

    Manzar Ashtari

    Full Text Available A phenomenon characterized by the experience of seeing light without any light actually entering the eye is called phosphenes or photopsias. Phosphenes can occur spontaneously or via induction by external stimuli. Previous reports regarding phosphenes have primarily focused on externally induced phosphenes such as by applying alternating or direct current to the cortex. A few of these reports used functional magnetic resonance (fMRI to study activations induced by cortical phosphenes. However, there are no fMRI reports on spontaneous phosphenes originating from the retina and the resulting pattern of cortical activations. We performed fMRI during a reversing checkerboard paradigm in three LCA patients who underwent unilateral gene therapy and reported experiencing frequent phosphene on a daily basis. We observed bilateral cortical activation covering the entire visual cortices when patients reported experiencing phosphenes. In contrast, in the absence of phosphenes, activation was regulated by patient's visual ability and demonstrated improved cortical activation due to gene therapy. These fMRI results illustrate the potential impact of phosphene perception on visual function and they may explain some of the variability that clinicians find in visual function testing in retinal degeneration. Although we did not perform correlations between visual function and phosphenes, we hope data presented here raises awareness of this phenomenon and its potential effect on visual function and the implications for clinical testing. We recommend a thorough history for phosphene experiences be taken in patients with retinal disease who are candidates for gene or molecular therapy. Lastly, these data illustrate the potential power of fMRI as an outcome measure of gene therapy and the negative impact phosphenes may have on vision testing. fMRI has proven to be a sensitive, non-invasive, and reproducible test paradigm for these purposes and can complement standard visual function testing.

  16. fMRI of Retina-Originated Phosphenes Experienced by Patients with Leber Congenital Amaurosis

    OpenAIRE

    Manzar Ashtari; Laura Cyckowski; Alborz Yazdi; Amanda Viands; Kathleen Marshall; István Bókkon; Albert Maguire; Jean Bennett

    2014-01-01

    A phenomenon characterized by the experience of seeing light without any light actually entering the eye is called phosphenes or photopsias. Phosphenes can occur spontaneously or via induction by external stimuli. Previous reports regarding phosphenes have primarily focused on externally induced phosphenes such as by applying alternating or direct current to the cortex. A few of these reports used functional magnetic resonance (fMRI) to study activations induced by cortical phosphenes. Howeve...

  17. [Hypercoagulable workup in ophthalmology. When and what].

    Science.gov (United States)

    Muñoz-Negrete, F J; Casas-Lleras, P; Pérez-López, M; Rebolleda, G

    2009-07-01

    Most ophthalmologic disorders secondary to hypercoagulabe state are due to the confluence of congenital and adquired factors. A systematic workup is mandatory. Most of congenital coagulation disorders cause venous trombosis and are inherited autosomal dominantly. In order of frequency these are factor V Leiden mutation (activated protein C resistance), G20210A mutation of the prothrombin gen and protein C, protein S, and antithrombin III deficiencies. Sickle cell anemia can determine arerial and venous thrombosis. In relation with arterial occlusion, the markers most frequently involved are homcysteine fasting levels and the markers of antiphospholipid antibody syndrome. Both of them can also determine venous thrombosis. Several acquired factors can lead to hypoercoagulable state, especially hyperhomocysteinemia, antiphospholipid antibody syndrome, hepatic disease, alcohol and tobacco intake, oral contraceptives, immobilization, surgeries and malignancies. In central venous occlusion is only necessary to rule out hyperhomocysteinemia and antiphospholipid antibody syndrome in young patients without known risk factors. In central artery occlusion, hypercoagulable workup is only recommended for patients less than 50 years-old with unknown emboli source. In this cases protein C, protein S, and antithrombin III deficiencies, homocystein, sickle cell disease and antiphospholipid antibody syndrome will ruled out. In non arteritic ischemic optic neuropathy hypercoagulable work up is not necessary. In amaurosis fugax without known emboli source, it is recommended to rule out etiologies of arterial occlusion, especially antithrombin III deficiencies, homocystein, sickle cell disease and antiphospholipid antibody syndrome. PMID:19658050

  18. Fifty-eight cases of ocular ischemic diseases caused by carotid artery stenosis

    Institute of Scientific and Technical Information of China (English)

    LUO Rong-jiang; LIU Shao-rui; LI Xiao-min; ZHUO Ye-hong; TIAN Zhen

    2010-01-01

    Background The blood supply to the eye comes from the retinal central vascular system of the ophthalmic artery and the ciliary vascular system. The ophthalmic artery stems from the ipsilateral internal carotid artery. If occlusion or stenosis occurs in the carotid artery, the blood perfusion to the ophthalmic artery becomes insufficient, leading to signs and symptoms of anterior and posterior ocular ischemia. The objective of this study was to evaluate the clinical characteristics and risk factors of ocular ischemic diseases caused by carotid artery stenosis.Methods This study was a retrospective review of 145 patients with carotid artery stenosis. Fifty-eight patients who had symptoms of ocular ischemic disease caused by carotid artery stenosis formed group A and the other 87 patients who only had carotid artery stenosis formed group B. We analyzed the causes and course of disease, and relative risk factors,by comparing the two groups.Results The degree of carotid artery stenosis in group A was higher than that in group B. And group A had a greater decrease of ophthalmic artery flow. Male, hypertension, hyperlipidemia, and smoking were significantly related to carotid artery stenosis. Amaurosis fugax was the most common ocular symptom in group A. The ocular ischemic diseases mainly included ischemic optic neuropathy, central/branch retinal artery occlusion, ophthalmoplegia externa, and ocular ischemic syndrome.Conclusions Carotid artery stenosis correlates with ocular ischemic diseases. Ophthalmologists must observe for ocular symptoms, which were the onset symptoms in some patients.

  19. CAROTID PLAQUE CLASSIFICATION USING CONTOURLET FEATURES AND SUPPORT VECTOR MACHINES

    Directory of Open Access Journals (Sweden)

    M. Thangavel

    2014-01-01

    Full Text Available The aim of this study is to propose a suitable and reliable system for better diagnosis and treatment of carotid diseases. In this study, Computer Aided Diagnosis (CAD system has been proposed for classifying carotid artery plaques using Contourlet features. Carotid images have been acquired for 124 subjects with symptoms (Amaurosis Fugax, Stroke or Transient Ischemic Attack and 133 subjects with no symptoms in the recent past. Images were normalized and plaque regions have been manually segmented by experts and these Region Of Interests (ROI have been used for further processing. Four level Contourlet transform has been applied to all ROIs and subimages were produced at different scales and orientations. Energy, Entropy, Mean and Standard deviation features were extracted from all the subimages. The feature selection has been done to select significant features and to ignore insignificant ones. Support Vector Machine classifier (SVM and Adaboost classifier have been applied to the selected features and plaques were classified as symptomatic or asymptomatic plaques. The contourlet features with Support vector machine classifier produced classification accuracy of 85.6% compared to 81.3% accuracy in Adaboost classifier. The classification results were compared with curvelet transform features and wavelet packet features. The contourlet with SVM classifier yielded better performance compared to curvelet and wavelet packet."

  20. Outpatient primary stent-PTA in a symptomatic internal carotid artery stenosis under protection

    International Nuclear Information System (INIS)

    In a 69 year old patient, with a symptomatic ICA stenosis a stent implantation was performed under outpatient conditions. An interdisciplinary consensus was reached that the patient was suitable for outpatient therapy. In accordance with the NASCET criteria, the patient was to be classified to the high-risk group. Within 120 days before the intervention, the following clinical symptoms had occurred: 1 TIA, 2 amaurosis fugax. In the diagnostic angiography a right postbulbar ICA stenosis of 97% was verified. The stent application and subsequent PTA were performed under protection using a filter system. The transfemoral route was always fitted with an endovascular closure system. The neck vessels were followed-up by means of colour coded duplex sonography (CCDS) on days 1, 30, 180 and 360. A contrast-medium intensified MRI was performed on the 5th day post-intervention. The implantation of the stent and PTA were done without any complications. Atheromatous plaque fragments were found in the protection system. A plaque embolism was excluded clinically and in the contrast-medium intensified MRI 5 days after the intervention. After 360 days, no restenosis was found in the CCDS, the ECA was perfused. The method presented is low in complications and shows a high success rate. If patient recruitment is adequate, this intervention can be performed on an outpatient basis. (orig.)

  1. Varied presentations of moyamoya disease in a tertiary care hospital of north-east India

    Directory of Open Access Journals (Sweden)

    Papori Borah

    2014-01-01

    Full Text Available Introduction: Moyamoya disease is a chronic progressive cerebrovascular disorder, characterized by stenosis or occlusion of bilateral internal carotid arteries (ICAs, anterior cerebral arteries (ACAs and middle cerebral arteries (MCAs, accompanied by a collateral network of vessels formed at the base of the brain. Ischemia and intracranial hemorrhage are the common typical manifestations. However moyamoya disease has been associated with atypical presentations like headache, seizures and involuntary movements. Although frequently reported from Asian countries like Japan, China and Korea, only few studies reported on clinical manifestations of moyamoya disease from India. Objectives: To study the varied presentations of moyamoya disease in a tertiary care hospital of north-east India. Material and Methods: Relevant investigations were done to rule out other causes of moyamoya syndrome. Results: We report 6 cases of moyamoya disease with varied presentations from a tertiary care referral government hospital. Case 1, 2 and 6 presented with alternating hemiparesis. Case 3 had amaurosis fugax. Case 4 had history suggestive of ischemic stroke and presented with hemichorea. Case 4 had focal seizure as the only manifestation. Cases 4 and 5 notably had stenosis of posterior cerebral artery (PCA in addition to stenosis of bilateral ICAs, ACAs and MCAs. Conclusion: Owing to its low incidence in India, moyamoya disease is easily overlooked as a possible diagnosis. However, because of its progressive nature, it is imperative to diagnose this disease early and offer surgical treatment to the patients.

  2. Computerized texture analysis of carotid plaque ultrasonic images can identify unstable plaques associated with ipsilateral neurological symptoms.

    Science.gov (United States)

    Kakkos, Stavros K; Nicolaides, Andrew N; Kyriacou, Efthyvoulos; Daskalopoulou, Stella S; Sabetai, Michael M; Pattichis, Constantinos S; Geroulakos, George; Griffin, Maura B; Thomas, Dafydd

    2011-05-01

    We estimated the value of objective, computerized texture analysis of ultrasonic images in distinguishing carotid plaques associated with neurological ipsilateral symptoms (amaurosis fugax [AmF; n = 30], transient ischemic attack [TIA; n = 52], and stroke [n = 55]) from asymptomatic plaques (n = 51). We performed 3 case-control studies (1/symptom with asymptomatic plaques as control). On logistic regression, AmF was independently associated with severity of stenosis, percentage of pixels with gray levels 0 to 10 (PPCS1; measure of echolucency), and spatial gray level dependence matrices (SGLDM) information measure of correlation (IMC-1; texture); TIAs with PPCS1 (echolucency), SGLDM correlation, and skewness (both texture); and stroke with PPCS1, SGLDM correlation, and percentage of pixels with gray levels 11 to 20 (PPCS2; echolucency). The area under the curve of the regression-derived predicted probability for AmF, TIA, and stroke was 0.92, 0.82, and 0.85, respectively (all P < .001). Texture analysis can identify carotid plaques associated with a neurological event, improving the diagnostic value of echolucency measures. Texture analyses could be applied to natural history studies. PMID:21474467

  3. Spontaneous internal carotid dissection in a 38-year-old woman: a case report

    Directory of Open Access Journals (Sweden)

    Kareem Abed

    2015-10-01

    Full Text Available This case report describes a patient found to have amaurosis fugax as a result of non-traumatic internal carotid dissection. Monocular blindness can be due to multiple causes including keratitis, acute glaucoma, vitreous hemorrhage, uveitis, retinal vascular occlusion, retinal detachment, optic neuropathy, trauma, or vascular malformations. In the setting of headache, neck pain, and an otherwise normal ophthalmic examination, this case report highlights the importance of recognizing transient ischemic attack and carotid artery dissection in the differential diagnosis. To further clarify the diagnosis, carotid ultrasound may aid diagnosis as was seen in this case, where decreased internal carotid artery velocities were found and subsequent CT angiography of the neck confirmed a diagnosis of carotid dissection. If a dissection is present, progression of symptoms may indicate impending cerebral infarction and warrant immediate attention. Antiplatelet therapy is the first-line treatment with anticoagulation, thrombolysis, and surgery reserved for cases of recurrent, progressive symptomatic episodes. Surgical options include endovascular repair such as angioplasty, stent placement, embolization, surgical revascularization, and bypass.

  4. Spontaneous internal carotid dissection in a 38-year-old woman: a case report.

    Science.gov (United States)

    Abed, Kareem; Misra, Amit; Vankawala, Viren

    2015-01-01

    This case report describes a patient found to have amaurosis fugax as a result of non-traumatic internal carotid dissection. Monocular blindness can be due to multiple causes including keratitis, acute glaucoma, vitreous hemorrhage, uveitis, retinal vascular occlusion, retinal detachment, optic neuropathy, trauma, or vascular malformations. In the setting of headache, neck pain, and an otherwise normal ophthalmic examination, this case report highlights the importance of recognizing transient ischemic attack and carotid artery dissection in the differential diagnosis. To further clarify the diagnosis, carotid ultrasound may aid diagnosis as was seen in this case, where decreased internal carotid artery velocities were found and subsequent CT angiography of the neck confirmed a diagnosis of carotid dissection. If a dissection is present, progression of symptoms may indicate impending cerebral infarction and warrant immediate attention. Antiplatelet therapy is the first-line treatment with anticoagulation, thrombolysis, and surgery reserved for cases of recurrent, progressive symptomatic episodes. Surgical options include endovascular repair such as angioplasty, stent placement, embolization, surgical revascularization, and bypass. PMID:26486115

  5. Amaurose bilateral por menigoencefalite criptocócica: relato de caso Bilateral amaurosis due to cryptococcus meningoencephalitis: case report

    Directory of Open Access Journals (Sweden)

    Ricardo Evangelista Marrocos de Aragão

    2008-02-01

    Full Text Available Meningoencefalite criptocócica é infecção causada por um fungo denominado Cryptococcus neoformans. Duas formas são conhecidas: variação gattii e neoformans. A infecção antes da puberdade é rara. Cerca de metade dos pacientes apresentam algum estado imunossupressivo. O papiledema está presente em um terço dos pacientes por ocasião do diagnóstico. Relatamos um caso de meningoencefalite por criptococose em paciente de oito anos de idade, sem relato de doenças prévias, que evoluiu com amaurose bilateral. O diagnóstico foi confirmado por detecção do C. neoformans, var. gattii. O paciente foi tratado com anfotericina B e dexametasona. Na literatura existem poucos relatos de perda visual permanente após meningite por criptococose. A existência de um protocolo para tratamento de pacientes com papiledema é um fator determinante para evitar a perda visual.Cryptococcal meningitis is caused by the yeast Cryptococcus neoformans. Two varieties are recognized: var. gattii and var. neoformans. It is usually associated with immunosuppressive states, particularly HIV infection. Cryptococcal infection of the central nervous system is uncommon in immunocompetent children and difficult to diagnose. Ocular complications are common. Optic disc swelling was found in 33%. The following report describes a case of meningitis caused by C. neoformans var. gattii in an 8 year-old immunocompetent child who developed optic atrophy. The patient was treated with amphotericin B associated with corticosteroids. Possible therapeutic strategies aimed at reducing visual loss in cryptococcal meningitis have great importance to avoid this important morbidity.

  6. Carotid ultrasonographic and brain computerized tomographic findings in patients with vascular ocular syndromes

    Energy Technology Data Exchange (ETDEWEB)

    Iwamoto, Toshihiko; Matsushima, Chikage; Shimizu, Souichirou; Takasaki, Masaru; Iwasaki, Takuya; Usui, Masahiko [Tokyo Medical Coll. (Japan)

    2002-02-01

    To clarify the characteristics of cerebrovascular lesions in subtypes of vascular ocular syndrome, including amaurosis fugax (AF), retinal artery occlusion (RAO), and retinal vein occlusion (RVO), 93 patients with vascular ocular syndrome were studied by means of carotid ultrasonography (US) and brain computerized tomography (CT). The subjects comprised 21 patients with AF, 37 with RAO, and 35 with RVO who were sequentially given these diagnoses by the department of ophthalmology. On the basis of US findings, carotid lesions were defined as the presence of plaque or stenotic changes. CT findings were assessed for the presence and distribution of low-density areas (LDAs). Mean age was similar in each group, ranging from 64.5 to 67.4 years. The RAO group had high rates of men, hypertension, and smokers. US showed that the prevalence of carotid lesions ipsilateral to the affected eye was high in the RAO group and that severe stenosis and ulcerated plaque were present in 28.6% of the AF group and 45.9% of the RAO group. On CT examination, cerebral infarctions appeared as LDAs in about 10% of the patients in each group, and the incidence and distribution of LDAs were similar. Of 13 patients with cerebral infarction, only 2 were presumably due to carotid lesions; the others had a variety of causes. The discrepancy between US and CT findings was attributed to the small number of patients with cerebral infarction, since most patients had visual defects as an initial symptom. Our results suggest that extracranial carotid lesions, considered to be a major risk factor for stroke, should be carefully assessed in patients with AF or RAO to prevent further stroke. (author)

  7. Hemodynamic and metabolic effects of cerebral revascularization.

    Science.gov (United States)

    Leblanc, R; Tyler, J L; Mohr, G; Meyer, E; Diksic, M; Yamamoto, L; Taylor, L; Gauthier, S; Hakim, A

    1987-04-01

    Pre- and postoperative positron emission tomography (PET) was performed in six patients undergoing extracranial to intracranial bypass procedures for the treatment of symptomatic extracranial carotid occlusion. The six patients were all men, aged 52 to 68 years. Their symptoms included transient ischemic attacks (five cases), amaurosis fugax (two cases), and completed stroke with good recovery (one case). Positron emission tomography was performed within 4 weeks prior to surgery and between 3 to 6 months postoperatively, using oxygen-15-labeled CO, O2, and CO2 and fluorine-18-labeled fluorodeoxyglucose. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rates for oxygen and glucose (CMRO2 and CMRGlu), and the oxygen extraction fraction (OEF) were measured in both hemispheres. Preoperatively, compared to five elderly control subjects, patients had increased CBV, a decreased CBF/CBV ratio, and decreased CMRO2, indicating reduced cerebral perfusion pressure and depressed oxygen metabolism. The CBF was decreased in only one patient who had bilateral carotid occlusions; the OEF, CMRGlu, and CMRO2/CMRGlu and CMRGlu/CBF ratios were not significantly different from control measurements. All bypasses were patent and all patients were asymptomatic following surgery. Postoperative PET revealed decreased CBV and an increased CBF/CBV ratio, indicating improved hemodynamic function and oxygen hypometabolism. This was associated with increased CMRO2 in two patients in whom the postoperative OEF was also increased. The CMRGlu and CMRGlu/CBF ratio were increased in five patients. Changes in CBF and the CMRO2/CMRGlu ratio were variable. One patient with preoperative progressive mental deterioration, documented by serial neuropsychological testing and decreasing CBF and CMRO2, had improved postoperative CBF and CMRO2 concomitant with improved neuropsychological functioning. It is concluded that symptomatic carotid occlusion is associated with altered

  8. Dissektion der Arteria carotis als Ursache ischämischer zerebrovaskulärer Ereignisse - Fallberichte und Diskussion

    Directory of Open Access Journals (Sweden)

    Tentschert S

    2003-01-01

    Full Text Available Dissektionen der kraniozervikalen Gefäße, inbesondere der Arteria carotis, zählen zu den häufigsten Ursachen ischämischer zerebrovaskulärer Ereignisse bei jüngeren Patienten. Die ischämische Symptomatik wird durch eine Wühlblutung in die Gefäßwand verursacht, welche entweder zu einer Minderung des zerebralen Blutflusses und/oder zu einer lokalen Thrombosierung mit nachfolgender Embolisation führt. Karotisdissektionen können durch ein mechanisches Trauma hervorgerufen werden, sie entstehen aber auch spontan oder sind dann bei einem Teil der Patienten mit Bindegewebserkrankungen assoziiert. Zu den häufigsten Symptomen zählen Kopfschmerzen, zervikaler Schmerz und Horner-Syndrom. Die zerebrale Ischämie führt meist zu einer transienten ischämischen Attacke (TIA oder zu einem ischämischen Infarkt im Stromgebiet der Arteria cerebri media der betroffenen Seite. Auch eine Amaurosis fugax kann auftreten. Trotz neuer technischer Möglichkeiten stellen Dissektionen der hirnversorgenden Gefäße nach wie vor eine diagnostische Herausforderung dar. Die digitale Subtraktionsangiographie gilt derzeit noch als Goldstandard zur Diagnostik, wird aber in vielen Fällen zunehmend durch neue nichtinvasive bildgebende Verfahren ersetzt oder ergänzt. Stenose oder Verschluß des betroffenen Gefäßes bilden sich in den meisten Fällen innerhalb von zwei Monaten nach dem Ereignis zurück. Therapeutische Maßnahmen haben vor allem die Verhinderung embolischer Komplikationen zum Ziel. Die gegenständliche Arbeit soll anhand von Fallbeispielen und einer Literaturübersicht klinisch relevante Aspekte und Probleme bei Diagnostik und Therapie der Dissektion der Arteria carotis aufzeigen.

  9. Vascular disorders in cerebral reversible ischaemic attacks

    International Nuclear Information System (INIS)

    In clinical prectice it is rather frequent to find neurological disorders whose etiology is not clear; in particular, it can be difficult to distinguish a cardiac from a more strictly neurological or vascular cause. In attempting to assess this problem, we have undertaken a study on 675 consecutive patients (387 males and 288 females), aged from 20 to 86 years. All patients, who came to our attention because of transient neurological symptoms or signs, underwent studies with Color Doppler Imaging and Doppler Spectral Analysis techniques applied to supraaortic vessels supplying cerebral regions. Our results show that the highest incidence of obstructive vascular findings (positive Doppler scans) is present in the age interval from 71 to 80 years (75%). The period of maximal incidence of pathologic findings is between 51 and 60 years of age (35% of the total), that is, in an age range where surgical therapy can be undertaken. In this decade 58% of examined patients showed abnormal Doppler scans. Short-lasting parcellar symptoms, such as dysphasia nominum and amaurosis fugax, or symptoms considered non-specific, such as loss of consciousness or dizziness, have given a rather high percentual incidence of positive scans; this is also the case with laterocervical murmurs, even if unaccompanied by symptoms. From the diagnostic viewpoint, Doppler imaging has reached its highest accuracy when applied to arteries very close to each other, as is the case with the carotid artery at its bifurcation. In addition, spectral analysis associated to Doppler imaging allows the detection of the frequency dispersion which results from flow turbulence caused by subcritical lesions in the presence of coiling and kinking of arterial vessel. In conclusion, noninvasive diagnostic methods based on Doppler technology (widely available commercially) can help to discriminate pathological cases in patients who present transient neurological disorders

  10. Carotid ultrasonographic and brain computerized tomographic findings in patients with vascular ocular syndromes

    International Nuclear Information System (INIS)

    To clarify the characteristics of cerebrovascular lesions in subtypes of vascular ocular syndrome, including amaurosis fugax (AF), retinal artery occlusion (RAO), and retinal vein occlusion (RVO), 93 patients with vascular ocular syndrome were studied by means of carotid ultrasonography (US) and brain computerized tomography (CT). The subjects comprised 21 patients with AF, 37 with RAO, and 35 with RVO who were sequentially given these diagnoses by the department of ophthalmology. On the basis of US findings, carotid lesions were defined as the presence of plaque or stenotic changes. CT findings were assessed for the presence and distribution of low-density areas (LDAs). Mean age was similar in each group, ranging from 64.5 to 67.4 years. The RAO group had high rates of men, hypertension, and smokers. US showed that the prevalence of carotid lesions ipsilateral to the affected eye was high in the RAO group and that severe stenosis and ulcerated plaque were present in 28.6% of the AF group and 45.9% of the RAO group. On CT examination, cerebral infarctions appeared as LDAs in about 10% of the patients in each group, and the incidence and distribution of LDAs were similar. Of 13 patients with cerebral infarction, only 2 were presumably due to carotid lesions; the others had a variety of causes. The discrepancy between US and CT findings was attributed to the small number of patients with cerebral infarction, since most patients had visual defects as an initial symptom. Our results suggest that extracranial carotid lesions, considered to be a major risk factor for stroke, should be carefully assessed in patients with AF or RAO to prevent further stroke. (author)

  11. Vasculitis cerebral cisticercosa y neuropatía óptica isquémica en una paciente con amaurosis unilateral y recuperación ad integrum

    OpenAIRE

    Enríquez Coronel,Guillermo; Santos Marcial,Edgar; Cabrera Aldana,Eibar Ernesto

    2004-01-01

    La cisticercosis es una parasitósis bien conocida que puede causar una gran cantidad de síndromes. La neuropatía isquémica-óptica es una enfermedad de adultos cuyas causas principales son hipertensión arterial y la diabetes y la arteritis de células gigantes. Presentamos el caso de una estudiante de medicina de 22 años que presentó súbitamente pérdida de la visión en el ojo derecho y después completa ceguera. Los estudios demostraron múltiples cisticercos en el hemisferio derecho. Fue tratada...

  12. Advantage of whole exome sequencing over allele-specific and targeted segment sequencing in detection of novel TULP1 mutation in leber congenital amaurosis

    DEFF Research Database (Denmark)

    Guo, Yiran; Prokudin, Ivan; Yu, Cong;

    2015-01-01

    targeted segment sequencing of 61 regions in 14 causative genes was performed. Subsequently, exome sequencing was undertaken in the proband, unaffected consanguineous parents and two unaffected siblings. Bioinformatic analysis used two independent pipelines, BWA-GATK and SOAP, followed by Annovar and Snp...

  13. Retinitis Pigmentosa

    Science.gov (United States)

    ... Congenital Amaurosis Macular Degeneration Retinitis Pigmentosa Stargardt Disease Usher Syndrome Other Retinal Diseases Glossary News & Research News & ... die. Forms of RP and related diseases include Usher syndrome, Leber’s congenital amaurosis, rod-cone disease, Bardet- ...

  14. Transient isolated brainstem symptoms preceding posterior circulation stroke: a population-based study

    Science.gov (United States)

    Paul, Nicola LM; Simoni, Michela; Rothwell, Peter M

    2013-01-01

    Summary Background Transient isolated brainstem symptoms (eg, isolated vertigo, dysarthria, diplopia) are not consistently classified as transient ischaemic attacks (TIAs) and data for prognosis are limited. If some of these transient neurological attacks (TNAs) are due to vertebrobasilar ischaemia, then they should be common during the days and weeks preceding posterior circulation strokes. We aimed to assess the frequency of TNAs before vertebrobasilar ischaemic stroke. Methods We studied all potential ischaemic events during the 90 days preceding an ischaemic stroke in patients ascertained within a prospective, population-based incidence study in Oxfordshire, UK (Oxford Vascular Study; 2002–2010) and compared rates of TNA preceding vertebrobasilar stroke versus carotid stroke. We classified the brainstem symptoms isolated vertigo, vertigo with non-focal symptoms, isolated double vision, transient generalised weakness, and binocular visual disturbance as TNAs in the vertebrobasilar territory; atypical amaurosis fugax and limb-shaking as TNAs in the carotid territory; and isolated slurred speech, migraine variants, transient confusion, and hemisensory tingling symptoms as TNAs in uncertain territory. Findings Of the 1141 patients with ischaemic stroke, vascular territory was categorisable in 1034 (91%) cases, with 275 vertebrobasilar strokes and 759 carotid strokes. Isolated brainstem TNAs were more frequent before a vertebrobasilar stroke (45 of 275 events) than before a carotid stroke (10 of 759; OR 14·7, 95% CI 7·3–29·5, p<0·0001), particularly during the preceding 2 days (22 of 252 before a vertebrobasilar stroke vs two of 751 before a carotid stroke, OR 35·8, 8·4–153·5, p<0·0001). Of all 59 TNAs preceding (median 4 days, IQR 1–30) vertebrobasilar stroke, only five (8%) fulfilled the National Institute of Neurological Disorders and Stroke (NINDS) criteria for TIA. The other 54 cases were isolated vertigo (n=23), non-NINDS binocular visual

  15. Non-traumatic neurological emergencies: imaging of cerebral ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Grunwald, Iris; Reith, Wolfgang [Department of Neuroradiology, Saarland University Clinic, Homburg/Saar (Germany)

    2002-07-01

    Cardiovascular disease is the leading cause of death worldwide with almost one-third of all cardiovascular deaths ascribed to stroke. Imaging modalities, such as CT, MRI, positron emission tomography (PET), and single photon emission CT (SPECT) provide tremendous insight into the pathophysiology of acute stroke. Computed tomography is considered the most important initial diagnostic study in patients with acute stroke, because underlying structural lesions, such as tumor, vascular malformation, or subdural hematoma, can mimic stroke clinically. Diffusion-weighted imaging (DWI) has the ability to visualize changes in diffusion within minutes after the onset of ischemia and has become a powerful tool in the evaluation of patients with stroke syndrome. Territories with diffusion and perfusion mismatch may define tissues at risk, but with potential recovery. An alternative strategy with CT technology uses rapid CT for dynamic perfusion imaging, with similar goals in mind. Angiography can be performed in the hyperacute stage if thrombolytic therapy is being considered. Indications for diagnostic angiography include transient ischemic attacks in a carotid distribution, amaurosis fugax, prior stroke in a carotid distribution, a high-grade stenotic lesion in a carotid artery, acquiring an angiographic correlation of magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) concerning stenotic findings. In 50% of all angiograms performed in the hyperacute stage, occlusion of a vessel is observed; however, the need for angiography has been made less necessary due to the improvements of MRA, duplex ultrasound, and CTA. Numerous etiologies can lead to infarction. In children, pediatric stroke is very uncommon. The most common cause is an embolus from congenital heart disease with right-to-left shunts. Also a dissection of large extracranial vessels may result in cerebral infarction, and although the brain is equipped with numerous venous drainage routes

  16. Non-traumatic neurological emergencies: imaging of cerebral ischemia

    International Nuclear Information System (INIS)

    Cardiovascular disease is the leading cause of death worldwide with almost one-third of all cardiovascular deaths ascribed to stroke. Imaging modalities, such as CT, MRI, positron emission tomography (PET), and single photon emission CT (SPECT) provide tremendous insight into the pathophysiology of acute stroke. Computed tomography is considered the most important initial diagnostic study in patients with acute stroke, because underlying structural lesions, such as tumor, vascular malformation, or subdural hematoma, can mimic stroke clinically. Diffusion-weighted imaging (DWI) has the ability to visualize changes in diffusion within minutes after the onset of ischemia and has become a powerful tool in the evaluation of patients with stroke syndrome. Territories with diffusion and perfusion mismatch may define tissues at risk, but with potential recovery. An alternative strategy with CT technology uses rapid CT for dynamic perfusion imaging, with similar goals in mind. Angiography can be performed in the hyperacute stage if thrombolytic therapy is being considered. Indications for diagnostic angiography include transient ischemic attacks in a carotid distribution, amaurosis fugax, prior stroke in a carotid distribution, a high-grade stenotic lesion in a carotid artery, acquiring an angiographic correlation of magnetic resonance angiography (MRA) or computed tomographic angiography (CTA) concerning stenotic findings. In 50% of all angiograms performed in the hyperacute stage, occlusion of a vessel is observed; however, the need for angiography has been made less necessary due to the improvements of MRA, duplex ultrasound, and CTA. Numerous etiologies can lead to infarction. In children, pediatric stroke is very uncommon. The most common cause is an embolus from congenital heart disease with right-to-left shunts. Also a dissection of large extracranial vessels may result in cerebral infarction, and although the brain is equipped with numerous venous drainage routes

  17. Manifestaciones oftalmológicas de la enfermedad cerebrovascular Ophthalmological manifestations of cerebrovascular disease

    Directory of Open Access Journals (Sweden)

    J. Gállego

    2008-01-01

    Full Text Available El ojo constituye una diana para la enfermedad vascular. El estudio de la microcirculación retiniana constituye una oportunidad muy interesante para la valoración del riesgo vascular al conocer la relación existente entre los cambios vasculares en la retina y el riesgo de padecer un ictus. Es además una ventana excepcional para conocer mejor la fisiopatología de la microcirculación. La arteria oftálmica es la primera rama de la arteria carótida interna. La afectación ocular puede ser uni o bilateral. Los síntomas oculares o neuro-oftalmológicos son transitorios o persistentes y sus manifestaciones son muy heterogéneas abarcando alteraciones de la agudeza visual, trastornos de los campos visuales, síndromes oculomotores y manifestaciones clínicas corticales y subcorticales complejas. Su conocimiento puede resultar clave para instaurar las medidas preventivas pertinentes o establecer el correcto diagnóstico y la aproximación diagnóstica inmediata, tan importante en la atención de los procesos vasculares cerebrales.Transient or persistent loss of vision in one eye is a common and distinctive manifestation of occlusive vascular disease. Occasionally, both eyes are involved together or sequentially, with temporary or even permanent blindness. The internal carotid arteries supply blood to the organ of vision; therefore pathologies of those arteries caused by arteriosclerosis may have a direct influence on its functioning. The most common syndromes are temporary (amaurosis fugax or constant reduction of visual acuity. In fundus examination central retinal artery occlusion and branch retinal artery occlusion are the most common diagnosis, while retinal vein occlusion, anterior ischemic optic neuropathy, ocular ischemic syndrome are less common. There are many clinical ophtlamological manifestations due to vascular brain damage. Proper recognition and diagnosis of the disease may protect the patient against serious life

  18. MRI plaque imaging detects carotid plaques with a high risk for future cerebrovascular events in asymptomatic patients.

    Directory of Open Access Journals (Sweden)

    Lorena Esposito-Bauer

    Full Text Available PURPOSE: The aim of this study was to investigate prospectively whether MRI plaque imaging can identify patients with asymptomatic carotid artery stenosis who have an increased risk for future cerebral events. MRI plaque imaging allows categorization of carotid stenosis into different lesion types (I-VIII. Within these lesion types, lesion types IV-V and VI are regarded as rupture-prone plaques, whereas the other lesion types represent stable ones. METHODS: Eighty-three consecutive patients (45 male (54.2%; age 54-88 years (mean 73.2 years presenting with an asymptomatic carotid stenosis of 50-99% according to ECST-criteria were recruited. Patients were imaged with a 1.5-T scanner. T1-, T2-, time-of-flight-, and proton-density weighted studies were performed. The carotid plaques were classified as lesion type I-VIII. Clinical endpoints were ischemic stroke, TIA or amaurosis fugax. Survival analysis and log rank test were used to ascertain statistical significance. RESULTS: Six out of 83 patients (7.2% were excluded: 4 patients had insufficient MR image quality; 1 patient was lost-to-follow-up; 1 patient died shortly after the baseline MRI plaque imaging. The following results were obtained by analyzing the remaining 77 patients. The mean time of follow-up was 41.1 months. During follow-up, n = 9 (11.7% ipsilateral ischemic cerebrovascular events occurred. Only patients presenting with the high-risk lesion types IV-V and VI developed an ipsilateral cerebrovascular event versus none of the patients presenting with the stable lesion types III, VII, and VIII (n = 9 (11.7% vs. n = 0 (0% during follow-up. Event-free survival was higher among patients with the MRI-defined stable lesion types (III, VII, and VIII than in patients with the high-risk lesion types (IV-V and VI (log rank test P<0.0001. CONCLUSIONS: MRI plaque imaging has the potential to identify patients with asymptomatic carotid stenosis who are particularly at risk of

  19. Carotid angioplasty with cerebral protection

    International Nuclear Information System (INIS)

    Background. Carotid endarterectomy (CEA) is widely used in the management of high-grade carotid stenosis. It is a surgical procedure requiring general anaesthesia and is suitable only for lesions located at or close to the carotid bifurcation. It may develop complications, such as stroke, death, cranial nerve palsies, wound haematoma and cardiac complications. The risk of complications is increased in patients with recurrent carotid artery stenosis following CEA, in subjects undergoing radiotherapy to the neck, and in patients with cardiopulmonary disease. The drawbacks of CEA have led physicians to search for alternative treatment options. Carotid angioplasty and stenting (CAS) is less invasive than CEA. The method is particularly suitable for the treatment of recurrent stenosis after previous CEA and distal internal artery stenosis, which is inaccessible for CEA. CAS does not cause cranial nerve palsies. Moreover, it does not require general anaesthesia and causes lower morbidity and mortality in patients with severe cardiopulmonary disease. The complications of CAS include stroke due to distal immobilisation of a plaque or thrombus dislodged during the procedure, abrupt vessel occlusion due to thrombosis, dissection or vasospasm, and restenosis due to intimal hyperplasia. CAS is a relatively new procedure; therefore, it is essential to establish its efficacy and safety before it is introduced widely into clinical practice. Patients and methods. In Slovenia, we have also started with carotid angioplasty by the study: Slovenian Carotid Angioplasty Study (SCAS). We performed CAS in 17 patients (12 males and 5 females) aged from 69 to 82 years. All patients were symptomatic with stenosis greater than 70 %. 10 patients suffered transient ischemic attacks, 4 patients minor strokes and 3 patients amaurosis fugax. Results. Technical success (< 30 % residual stenosis) was achieved in all cases. In 14 patients, no residual stenosis was found, in 2 patients a 15 % residual

  20. CLINICAL STUDY OF RETINAL VEIN OCCLUSIONS AND MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Satyavathi

    2015-01-01

    Full Text Available Retinal vein occlusion is the most common retinal occlusive disorder encountered by Ophthalmologists and is usually associated with a variable amount of visual loss. This is the second most common retinal vascular disease next to diabetic retinopathy. Liebreich initially described dramatic obstruction of veins as retinal apoplexy. Leber ( 1 (1877 reported the first case of BRVO and called it Hem orrhagic retinitis. RVO most commonly affects the venous blood supply of the entire retina (CRVO or a quadrant drained by one of the branches (BRVO or less commonly the superior or inferior half of the retina alone is affected (HCRVO. For discussion and management purpose RVO is broadly classified into six clinical entities includes (1 Non - ischemic CRVO (2 Ischemic CRVO (3 Non ischemic HCRVO (4Ischemic HCRVO (5 Major BRVO (6Macular BRVO. So much of confusion still exists regarding its natural histo ry, degree of severity, management and its progression. The clinical study of RVO is taken up mainly with a view to study the importance of systemic risk factors in etiopathogenisis of RVO, to study the clinical features and effectiveness of treatment in m odification of the natural course and complications of RVO. Depending on type of venous occlusion patient may present with loss of central vision frequently noticed on waking up in the morning, or field contraction, erythropsia, floates, black spots. Episo des of amaurosis fugax lasts for minutes to hours may be present. There may be metamor - phopsia. Signs of decreased visual acuty, RAPD, visual field defects are observed. Fundus picture shows Retinal hemorrhages distributed based on type of venous occlusion . In ischemic CRVO the picture shows “berries on a twig”. Various sequel & complications include macular edema, anterior segment and retinal neovascularisation, vitreous hemorrhage, retinal detachment may be encountered. Various risk factors include Hypert ension, Diabetes, Hyper lipidemia, IHD

  1. Investigation of the initial symptom, onset time and predisposing factors of acute cerebral haemorrhage%急性出血性脑血管疾病相关因素分析

    Institute of Scientific and Technical Information of China (English)

    曹非; 骆芳; 胡波; 魏桂荣; 许辉; 菜敬杰

    2008-01-01

    Objective To investigate the initial symptoms, onset time and predisposing factors of acute cerebral haemorrhage in order to more effectively prevent cerebral haemorrhage. Methods 728 cases with acute cerebral haemorrhage were collected in recent 8 years. The initial symptoms,onset time and predisposing factors of all the patients were investigated. Results Acute cerebral haemorrhage in 582 caces (79.9%) occurred at time between 6am and 18pm and 146 cases (20%) at night. The main predisposing causes of acute cerebral haemorrhage were the playing of chess, cards and mahjong (16.1%), quarrels (12.8%), overwork (11.7%), alcoholism (7.2%) and so on. The most common initial symptom was hemianesthesia, accounting for 16.2%, others were vertigo (13.0%), headache ( 11.4%), amaurosis fugax ( 9.3%), speech ambiguity ( 8.6%) and transitory visual disturbance (7.9%). Conclusions The preventive measures of cerebral haemorrhage should be focused on daytime, especially in the morning. Sixteen locations where the cerebral haemorrhage is prone to happen should be paid more attention to by the patients with hypertension and the medical staff. Thirteen symptoms,such as hemianesthesia and vertigo,are the aurae of cerebral haemorrhage.%目的 调查急性脑出血患者首发症状、发病时间和诱因,旨在更有效预防脑出血发病.方法 搜集调查近8年728例脑出血患者临床资料,分析其首发症状、发病时问和诱因. 结果 6:00~18:00发病582例占79.9%.18:00~6:00发病146例,占20.0%.脑出血发病第1位诱因是麻将棋牌,达117例,占16.1%,其次分别为争吵93例(12.8%),过劳85例(11.7%),酗酒53例(7.2%)等.首发症状最多见的足偏身麻木,118例,占16.2%;其次为突发眩晕,其他排列顺序依次为:头痛、一过性黑朦、言语含糊、短暂性视力障碍. 结论 脑出血发病预防重点应放在白天,尤其是上午;16种脑出血好发诱因应引起高血压患者和医务人员的重视,偏身麻木、眩晕等13

  2. A synopsis of the Malesian species of Kibara (Monimiaceae)

    NARCIS (Netherlands)

    Philipson, W.R.

    1985-01-01

    Thirty-nine species are recognized of which twenty-four are described as new ( K. bullata, K. carrii, K. chimbuensis, K. ferox, K. flagelliformis, K. fragrans, K. fugax, K. hartleyi, K. karengana, K. katikii, K. kostermansii, K. latifolia, K. leachii, K. macrantha, K. nitens, K. novobritanica, K. ob

  3. Mutation Discovered in a Feline Model of Human Congenital Retinal Blinding Disease

    OpenAIRE

    Menotti-Raymond, Marilyn; Deckman, Koren Holland; David, Victor; Myrkalo, Jaimie; O'Brien, Stephen J.; Narfström, Kristina

    2010-01-01

    The authors report on the genetic characterization of a deletion in the feline CRX gene in the Rdy cat, defining a new large-animal model for Leber congenital amaurosis, retinitis pigmentosa, and cone–rod dystrophy.

  4. Glaucoma

    Medline Plus

    Full Text Available ... Funding Division of Extramural Affairs Division of Extramural Science Programs Funding Opportunity Announcements Funding Mechanisms Supported by ... Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube Videos: Glaucoma NEI ...

  5. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... Funding Division of Extramural Affairs Division of Extramural Science Programs Funding Opportunity Announcements Funding Mechanisms Supported by ... Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube Videos: Amblyopia NEI ...

  6. Glaucoma

    Medline Plus

    Full Text Available ... Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars ... in Spanish (Información en español) Website, Social Media Policies and Other Important Links FAQ NEI Employee Emergency ...

  7. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish ... in Spanish (Información en español) Website, Social Media Policies and Other Important Links FAQ NEI Employee Emergency ...

  8. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... Funding Division of Extramural Activities Division of Extramural Science Programs Funding Opportunity Announcements Funding Mechanisms Supported by ... Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube Videos: Amblyopia NEI ...

  9. Glaucoma

    Medline Plus

    Full Text Available ... Funding Division of Extramural Activities Division of Extramural Science Programs Funding Opportunity Announcements Funding Mechanisms Supported by ... Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube Videos: Glaucoma NEI ...

  10. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... NEI All Research at NEI Office of the Scientific Director Office of the Clinical Director Education Programs ... Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube Videos: Amblyopia NEI ...

  11. Glaucoma

    Medline Plus

    Full Text Available ... NEI All Research at NEI Office of the Scientific Director Office of the Clinical Director Education Programs ... Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube Videos: Glaucoma NEI ...

  12. Retinoschisis (Juvenile)

    Science.gov (United States)

    ... Congenital Amaurosis Macular Degeneration Retinitis Pigmentosa Stargardt Disease Usher Syndrome Other Retinal Diseases Glossary News & Research News & ... affected by retinitis pigmentosa, age-related macular degeneration, Usher syndrome and the entire spectrum of retinal diseases. ...

  13. Other Retinal Diseases

    Science.gov (United States)

    ... Congenital Amaurosis Macular Degeneration Retinitis Pigmentosa Stargardt Disease Usher Syndrome Other Retinal Diseases Glossary News & Research News & ... affected by retinitis pigmentosa, age-related macular degeneration, Usher syndrome and the entire spectrum of retinal diseases. ...

  14. Stargardt Disease

    Science.gov (United States)

    ... Congenital Amaurosis Macular Degeneration Retinitis Pigmentosa Stargardt Disease Usher Syndrome Other Retinal Diseases Glossary News & Research News & ... for retinal degenerative diseases like retinitis pigmentosa (RP), Usher syndrome and macular degeneration . Back to top What ...

  15. NEI You Tube Videos: Amblyopia

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    Full Text Available ... Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube Videos: Amblyopia NEI ... questions and comments to the NEI Office of Science Communications, Public Liaison, and Education. Technical questions about ...

  16. Glaucoma

    Medline Plus

    Full Text Available ... Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube Videos: Glaucoma NEI ... questions and comments to the NEI Office of Science Communications, Public Liaison, and Education. Technical questions about ...

  17. NEI You Tube Videos: Amblyopia

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    Full Text Available ... Health Education Program Diabetic Eye Disease Education Program Glaucoma Education Program Low Vision Education Program Spanish-language ... Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision ...

  18. NEI You Tube Videos: Amblyopia

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    Full Text Available ... Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube Videos: Amblyopia NEI ...

  19. Glaucoma

    Medline Plus

    Full Text Available ... Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube Videos: Glaucoma NEI ...

  20. Pain Management in Functional Gastrointestinal Disorders

    OpenAIRE

    Vigano, Antonio; Bruera, Eduardo

    1995-01-01

    Pain is a common feature in functional gastrointestinal disorders (FGID). An abnormally low visceral sensory threshold, as well as a number of central, spinal and peripheral pain-modulating abnormalities, have been proposed for this syndrome. Clinical aspects of pain associated with irritable esophagus, functional dyspepsia, biliary dysmotility, inflammatory bowel syndrome and proctalgia fugax are reviewed. Because of its unclear pathophysiology, pain expression is the main target for the suc...

  1. A synopsis of the Malesian species of Kibara (Monimiaceae)

    OpenAIRE

    Philipson, W.R.

    1985-01-01

    Thirty-nine species are recognized of which twenty-four are described as new ( K. bullata, K. carrii, K. chimbuensis, K. ferox, K. flagelliformis, K. fragrans, K. fugax, K. hartleyi, K. karengana, K. katikii, K. kostermansii, K. latifolia, K. leachii, K. macrantha, K. nitens, K. novobritanica, K. oblongata, K. rosselensis, K. royenii, K. shungolensis, K. sleumeri, K. streimannii, K. sudestensis, and K. versteeghii) ). One new combination is made: K. oligocarpella (Kaneh. & Hatus.) Philipson, ...

  2. 77 FR 48162 - Announcement of Requirements and Registration for the Challenge To Identify Audacious Goals in...

    Science.gov (United States)

    2012-08-13

    ... powerful influence on the NEI mission. The evaluation process will begin by de-identifying the entries and... inherited form of childhood blindness in less than 10 years. The first genetic mutations causing Lebers Congenital Amaurosis, a rare form of inherited childhood blindness, were identified in 1997....

  3. NEI You Tube Videos: Amblyopia

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    Full Text Available ... Macular Degeneration Amblyopia Animations Blindness Cataract Convergence Insufficiency Diabetic Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube ...

  4. Glaucoma

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    Full Text Available ... Macular Degeneration Amblyopia Animations Blindness Cataract Convergence Insufficiency Diabetic Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube ...

  5. Permanent genetic resources added to molecular ecology resources database 1 April 2013-31 May 2013.

    Science.gov (United States)

    Agostini, Cecilia; Albaladejo, R G; Aparicio, A; Arthofer, Wolfgang; Berrebi, P; Boag, Peter T; Carbone, Ignazio; Conroy, Gabriel C; Cortesero, A M; Costa Gonçalves, Evonnildo; Costa, Diogo; Couto, Alvarina; De Girolamo, Mirko; Du, Hao; Fu, Shi-Jian; Garrido-Garduño, T; Gettová, L; Gilles, A; Guerreiro Hamoy, Igor; Herrera, C M; Heussler, Carina; Isidro, Eduardo; Josso, C; Krapf, Patrick; Lamont, Robert W; Le Ralec, A; Lopes, Susana; Luís, Carla; Luo, Hui; Mahéo, F; Marino, Ilaria A M; Mieuzet, L; Murray, Brent W; Ogbourne, Steven M; Pallavicini, Alberto; Parejo-Farnés, C; Patarnello, Tomaso; Paty, C; Pereira, Carolina; Pinho, Catarina; Pinto, Pablo; Poinsot, D; Powell, Adrienne; Putman, Alexander I; Santoro, André; Santos, Sidney; Schlick-Steiner, Birgit C; Scott, Candace; Silvanira Barbosa, Maria; Šimková, A; Simon, J-C; Solé-Cava, Antonio; Steiner, Florian M; Sun, Zhengxin; Torboli, Valentina; Tredway, Lane P; Van Coeverden de Groot, Peter J; Vasconcellos, Anderson; Vázquez-Domínguez, E; Wang, Deng-Qiang; Wang, Yu-Xiang; Wei, Qi-Wei; Zane, Lorenzo; Zhang, Shu-Huan

    2013-09-01

    This article documents the addition of 234 microsatellite marker loci to the Molecular Ecology Resources Database. Loci were developed for the following species: Acipenser sinensis, Aleochara bilineata, Aleochara bipustulata, Barbus meridionalis, Colossoma macropomum, Delia radicum, Drosophila nigrosparsa, Fontainea picrosperma, Helianthemum cinereum, Liomys pictus, Megabalanus azoricus, Pelteobagrus vachelli, Pleuragramma antarcticum, Podarcis hispanica type 1A, Sardinella brasiliensis and Sclerotinia homoeocarpa. These loci were cross-tested on the following species: Acipenser dabryanus, Barbus balcanicus, Barbus barbus, Barbus cyclolepis, Drosophila hydei, Drosophila melanogaster, Drosophila obscura, Drosophila subobscura, Fontainea australis, Fontainea fugax, Fontainea oraria, Fontainea rostrata, Fontainea venosa, Podarcis bocagei, Podarcis carbonelli, Podarcis liolepis, Podarcis muralis and Podarcis vaucheri. PMID:23937578

  6. New concept of functional anorectal disorders. In relation to newly published ROME III

    International Nuclear Information System (INIS)

    In newly published Rome III, Functional anorectal disorders are divided into 7 disorders. F1 Functional fecal incontinence is divided into staining, soiling, seepage and leakage in the degree and urge and passive incontinences in the dynamics, of which the former is dysfunction of the rectum and the latter of the anus. For the treatment, the most effective is biofeedback therapy (BF). F2 Functional anorectal pain is divided into F2a Chronic proctalgia, F2a1 Levator ani syndrome, F2a2 Unspecified functional anorectal pain and F2b Proctalgia fugax. F2a1 Levator ani syndrome is defined as a pain caused by traction of the levator ani, but in my experience, only 4 (3.5%) among 116 cases accorded to the criteria making us dubious of the definition. As for F2b Proctalgia fugax, the cause has not yet been found. In these two F2a, various treatments are tried without significant effectiveness due perhaps to the unknown pathogenesis which I assume to be the neuralgia of pudendal nerve. F3 Functional defecation disorders consist of F3a Dyssynergic defecation and F3b Inadequate defecatory propulsion of which, the former is caused by paradoxical contraction or inadequate relaxation of the pelvic floor muscles and the latter caused by inadequate propulsive force in defecation. Their treatments are BF and defecatory enforcement. (author)

  7. Antibody Neutralization Poses a Barrier to Intravitreal Adeno-Associated Viral Vector Gene Delivery to Non-Human Primates

    OpenAIRE

    Kotterman, Melissa A.; Yin, Lu; Strazzeri, Jennifer M.; Flannery, John G; Merigan, William H.; Schaffer, David V

    2014-01-01

    Gene delivery vectors based on adeno-associated viruses (AAV) have exhibited promise in both preclinical disease models and human clinical trials for numerous disease targets, including the retinal degenerative disorders Leber's congenital amaurosis and choroideremia. One general challenge for AAV is that pre-existing immunity, as well as subsequent development of immunity following vector administration, can severely inhibit systemic AAV vector gene delivery. However, the role of neutralizin...

  8. Acute encephalopathy with bilateral thalamotegmental involvement and a benign course: a case report from Brazil

    OpenAIRE

    Alvarenga, Regina Maria Papais; Neri, Vanderson Carvalho; Mendonça, Tatiane; Camargo, Solange

    2011-01-01

    This rare encephalopathy that generally affects children is preceded by a respiratory infection and fever associated with convulsions and may progress to coma. Outcome is catastrophic in most cases. This case report describes a Brazilian child of African descent with fever, cephalea and bilateral amaurosis, who evolved to coma with pyramidal signs and associated convulsions. MRI showed diffuse, symmetrical lesions in the thalamotegmental region and brainstem. Following administration of methy...

  9. Distilling a Visual Network of Retinitis Pigmentosa Gene-Protein Interactions to Uncover New Disease Candidates

    OpenAIRE

    Daniel Boloc; Sergio Castillo-Lara; Gemma Marfany; Roser Gonzàlez-Duarte; Abril, Josep F

    2015-01-01

    BACKGROUND: Retinitis pigmentosa (RP) is a highly heterogeneous genetic visual disorder with more than 70 known causative genes, some of them shared with other non-syndromic retinal dystrophies (e.g. Leber congenital amaurosis, LCA). The identification of RP genes has increased steadily during the last decade, and the 30% of the cases that still remain unassigned will soon decrease after the advent of exome/genome sequencing. A considerable amount of genetic and functional data on single RD g...

  10. Pathological, clinical and biochemical investigation of naturally occurring pregnancy toxemia of sheep

    OpenAIRE

    Kabakci N.; Yarim G.; Yarim M.; Duru O.; Yagci B.; Kisa U.

    2003-01-01

    A sick ewe in late pregnancy presented with clinical incoordination lipping, amaurosis, head tilt gait and nervous symptoms such as circling movements. A smell of ketones on the breath was detected. The sick animal died during clinical examination and, together with three more dead animals belonging to the same flock, was submitted to the laboratory for necropsy. The uteri of all pregnant animals contained late-term twin fetuses. The most prominent lesion was extensive fatty infiltration of t...

  11. Tackling Inherited Blindness

    OpenAIRE

    Batten, Matthew L.; Imanishi, Yoshikazu; Tu, Daniel C; Doan, Thuy; Zhu, Li; Pang, Jijing; Glushakova, Lyudmila; Moise, Alexander R.; Baehr, Wolfgang; Van Gelder, Russell N.; Hauswirth, William W.; Rieke, Fred; Palczewski, Krzysztof

    2005-01-01

    Background Leber congenital amaurosis (LCA), a heterogeneous early-onset retinal dystrophy, accounts for ~15% of inherited congenital blindness. One cause of LCA is loss of the enzyme lecithin:retinol acyl transferase (LRAT), which is required for regeneration of the visual photopigment in the retina. Methods and Findings An animal model of LCA, the Lrat −/− mouse, recapitulates clinical features of the human disease. Here, we report that two interventions—intraocular gene therapy and oral ph...

  12. Complications associated with prone positioning in elective spinal surgery

    OpenAIRE

    DePasse, J. Mason; Mark A Palumbo; Haque, Maahir; Eberson, Craig P.; Alan H Daniels

    2015-01-01

    Complications associated with prone surgical positioning during elective spine surgery have the potential to cause serious patient morbidity. Although many of these complications remain uncommon, the range of possible morbidities is wide and includes multiple organ systems. Perioperative visual loss (POVL) is a well described, but uncommon complication that may occur due to ischemia to the optic nerve, retina, or cerebral cortex. Closed-angle glaucoma and amaurosis have been reported as addit...

  13. A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene.

    OpenAIRE

    Sohocki, M M; Sullivan, L S; Mintz-Hittner, H A; Birch, D.; Heckenlively, J R; Freund, C L; McInnes, R R; Daiger, S P

    1998-01-01

    Mutations in the retinal-expressed gene CRX (cone-rod homeobox gene) have been associated with dominant cone-rod dystrophy and with de novo Leber congenital amaurosis. However, CRX is a transcription factor for several retinal genes, including the opsins and the gene for interphotoreceptor retinoid binding protein. Because loss of CRX function could alter the expression of a number of other retinal proteins, we screened for mutations in the CRX gene in probands with a range of degenerative re...

  14. The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy

    OpenAIRE

    Peluso Ivana; Conte Ivan; Testa Francesco; Dharmalingam Gopuraja; Pizzo Mariateresa; Collin Rob WJ; Meola Nicola; Barbato Sara; Mutarelli Margherita; Ziviello Carmela; Barbarulo Anna Maria; Nigro Vincenzo; Melone Mariarosa AB; Simonelli Francesca; Banfi Sandro

    2013-01-01

    Abstract Background Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy i...

  15. Inherited Retinal Degenerative Disease Registry

    Science.gov (United States)

    2016-03-21

    Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

  16. A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction

    OpenAIRE

    Henderson, R. H.; Williamson, K.A; Kennedy, J. S.; Webster, A. R.; Holder, G E; Robson, A. G.; Fitzpatrick, D R; van Heyningen, V; Moore, A T

    2009-01-01

    Purpose: To describe the clinical findings of a patient with an early onset retinal dystrophy and a novel mutation in OTX2, and to compare these findings with previously reported cases.Methods: Using direct sequencing, we screened 142 patients, who had either Leber congenital amaurosis (LCA) or early onset retinal dystrophy (EORD), for mutations in OTX2. All patients received a detailed ophthalmic examination including electroretinography and retinal imaging.Results: Only one mutation in OTX2...

  17. A rare de novo nonsense mutation in OTX2 causes early onset retinal dystrophy and pituitary dysfunction

    OpenAIRE

    Henderson, Robert H; Williamson, Kathleen A.; Kennedy, Joanna S.; Webster, Andrew R.; Holder, Graham E.; Robson, Anthony G.; FitzPatrick, David R.; van Heyningen, Veronica; Moore, Anthony T.

    2009-01-01

    To describe the clinical findings of a patient with an early onset retinal dystrophy and a novel mutation in OTX2, and to compare these findings with previously reported cases.Methods: Using direct sequencing, we screened 142 patients, who had either Leber congenital amaurosis (LCA) or early onset retinal dystrophy (EORD), for mutations in OTX2. All patients received a detailed ophthalmic examination including electroretinography and retinal imaging.Results: Only one mutation in OTX2 was iden...

  18. CRB1 mutations in inherited retinal dystrophies.

    OpenAIRE

    Bujakowska, Kinga; Audo, Isabelle; Mohand-Saïd, Saddek; Lancelot, Marie-Elise; Antonio, Aline; Germain, Aurore; Léveillard, Thierry; Letexier, Mélanie; Saraiva, Jean-Paul; Lonjou, Christine; Carpentier, Wassila; Sahel, José-Alain; Bhattacharya, Shomi; Zeitz, Christina

    2012-01-01

    Mutations in the CRB1 gene are associated with variable phenotypes of severe retinal dystrophies, ranging from leber congenital amaurosis (LCA) to rod-cone dystrophy, also called retinitis pigmentosa (RP). Moreover, retinal dystrophies resulting from CRB1 mutations may be accompanied by specific fundus features: preservation of the para-arteriolar retinal pigment epithelium (PPRPE) and retinal telangiectasia with exudation (also referred to as Coats-like vasculopathy). In this publication, we...

  19. RDH12 retinopathy: novel mutations and phenotypic description

    OpenAIRE

    Mackay, D. S.; Borman, A. D.; Moradi, P; Henderson, R. H.; Li, Z.; Wright, G. A.; Waseem, N; M. Gandra; Thompson, D.A.; Bhattacharya, S S; Holder, G E; Webster, A. R.; Moore, A T

    2011-01-01

    Purpose: To identify patients with autosomal recessive retinal dystrophy caused by mutations in the gene, retinal dehydrogenase 12 (RDH12), and to report the associated phenotype.Methods: After giving informed consent, all patients underwent full clinical evaluation. Patients were selected for mutation analysis based upon positive results from the Asper Ophthalmics Leber congenital amaurosis arrayed primer extansion (APEX) microarray screening, linkage analysis, or their clinical phenotype. A...

  20. Functional characteristics of patients with retinal dystrophy that manifest abnormal parafoveal annuli of high density fundus autofluorescence; a review and update

    OpenAIRE

    Robson, Anthony G.; Michaelides, Michel; Saihan, Zubin; Bird, Alan C.; Webster, Andrew R.; Moore, Anthony T.; Fitzke, Fred W; Holder, Graham E.

    2007-01-01

    Purpose To examine the presence and functional significance of annular fundus autofluorescence abnormalities in patients with different retinal dystrophies. Methods Eighty one patients were ascertained who had a parafoveal ring of high density on fundus autofluorescence imaging. Sixty two had had a clinical diagnosis of retinitis pigmentosa (RP) or Usher syndrome with normal visual acuity. Others included a case of Leber congenital amaurosis and genetically confirmed cases of cone or cone-rod...

  1. Senior-Løken Syndrome: A syndromic form of retinal dystrophy associated with nephronophthisis

    OpenAIRE

    Ronquillo, C.C.; Bernstein, P S; Baehr, W

    2012-01-01

    Senior-Løken syndrome (SLS) is an autosomal recessive disease characterized by development of a retinitis pigmentosa (RP)- or Leber congenital amaurosis (LCA)-like retinal dystrophy and a medullary cystic kidney disease, nephronophthisis. Mutations in several genes (called nephrocystins) have been shown to cause SLS. The proteins encoded by these genes are localized in the connecting cilium of photoreceptor cells and in the primary cilium of kidney cells. Nephrocystins are thought to have a r...

  2. Congenital retinal dystrophies: a study of early cognitive and visual development.

    OpenAIRE

    Black, M M; Sonksen, P M

    1992-01-01

    The reported incidence of mental retardation in Leber's congenital amaurosis has varied from 10% to 87%. There has been no review of the estimate since it became possible to delineate an increasing number of diagnostic subcategories. In this study, the visual and cognitive development of 38 children with congenital retinal dystrophies has been followed up prospectively. Children with associated disorders in other systems and those with central nervous system malformations or degenerations wer...

  3. Novel mutations in two Saudi patients with congenital retinal dystrophy

    OpenAIRE

    Leen Abu Safieh; Humoud M Al-Otaibi; Richard Alan Lewis; Igor Kozak

    2016-01-01

    To report novel mutations in two Saudi children with clinical features of Leber congenital amaurosis (LCA) and Alström syndrome. Case reports. Case 1 was a child with phenotypic features of LCA including oculodigital sign, bilateral enophthalmos, nystagmus, pale disc, and retinal changes. Direct sequencing of the coding sequence of GUCY2D revealed a missense mutation affecting highly conserved position (c. 743C > T; p.S248 L). Case 2 describes a girl with marked nystagmus, photophobia, and re...

  4. Naturally Occurring Animal Models with Outer Retina Phenotypes

    OpenAIRE

    Baehr, Wolfgang; Frederick, Jeanne M.

    2009-01-01

    Naturally occurring and laboratory generated animal models serve as powerful tools with which to investigate the etiology of human retinal degenerations, especially retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), cone dystrophies (CD) and macular degeneration (MD). Much progress has been made in elucidating gene defects underlying disease, in understanding mechanisms leading to disease, and in designing molecules for translational research and gene-based therapy to interfere with...

  5. RE-EDUCATIVE METHOD IN THE PROCESS OF MINIMIZING OF AUTOAGRESIVE WAYS OF BEHAVIOR

    OpenAIRE

    Nenad GLUMBIC; Kosa NIKOLIC

    1999-01-01

    Autoagressive behavior is a relatively frequent symptom of mental disturbances and behavior disturbances which are the subject of professional engagement of clinically oriented defectologists. In the process of rehabilitation numerous methods are used, from behavioral to psychopharmacological ones by which the above mentioned problems are eliminated of softened.The paper deals with four children with different diagnosis (autism, disintegrative psychosis, Patau syndrome and amaurosis) that hav...

  6. Moraea intermedia and M. vuvuzela (Iridaceae-Iridoideae, two new species from western South Africa, and some nomenclatural changes and range extensions in the genus

    Directory of Open Access Journals (Sweden)

    P. Goldblatt

    2010-12-01

    Full Text Available We describe two new species in the largely sub-Saharan genus Moraea Mill. (± 205 spp. from its centre of diversity in the winter rainfall region of southern Africa. Moraea intermedia, from north-central Namaqualand near Springbok, is a member of the small section Tubiflorae (now eight species, remarkable in its growth habit with a long basal intemode. leaves clustered at the first aerial node, and Moraea-type stamens and style branches but subequal tepals with very short claws that clasp only the base of the filament column. Moraea vuvuzela. a member of series Galaxia of the Galaxia group of the genus (now 17 species, has deeply fringed stigma lobes, filaments free in the upper 1 mm, ± prostrate, lanceolate leaves and. remarkable for the series, dark brown to purple markings near the base of the tepal limbs. In the unusually variable M.fugax, currently with two subspecies, new collections of subsp. fugax co-occurring but on different soils with subsp.  filicaulis, cast doubt on their current treatment as members of the same species. We now favour recognition of the diminutive subsp.filicaulis as a separate species, M. filicaulis. In the M iripetala group we recommend recognition of the early blooming M. punctata, described in 1892 and later subsumed in M. iripetala but readily distinguished by the long inner  tepals broader in the midline and short, relatively broad, plane rather than channelled leaves. We also report small but significant range extensions for M. barkerae, M. macrocarpa and M. tricolor.

  7. A Phe-rich region in short-wavelength sensitive opsins is responsible for their aggregation in the absence of 11-cis-retinal

    OpenAIRE

    Zhang, Tao; Fu, Yingbin

    2013-01-01

    Human blue and mouse S-opsin are prone to aggregation in the absence of 11-cis-retinal, which underlie the rapid cone degeneration in human patients and animal models of Leber congenital amaurosis (LCA). By in silico analysis and domain swapping experiments, we show that a Phe-rich region in short-wavelength sensitive (SWS) opsins, but not in medium/long-wavelength sensitive opsins, is responsible for SWS opsin aggregation. Mutagenesis studies suggest that Phe residues in this region are crit...

  8. La terapia génica marca un hito al proporcionar visión a adultos jóvenes casi ciegos

    OpenAIRE

    Shaberman, Ben A.

    2008-01-01

    Artículo original publicado en la página web de la Foundation Fighting Blindness (USA) el 28 Abr. 2008 (www.westernclassic.org). Traducido por José Martín Nieto. Tres jóvenes adultos prácticamente sin visión pueden ahora leer varias líneas de letras en un optotipo y ver mejor en condiciones de luz baja, gracias a una terapia génica innovadora dirigida a revertir la ceguera en una forma severa de retinosis pigmentaria, conocida como Amaurosis Congénita de Leber (LCA). Una de las tres person...

  9. The Inherited Blindness Protein AIPL1 Regulates the Ubiquitin-Like FAT10 Pathway

    OpenAIRE

    Bett, John S.; Naheed Kanuga; Emma Richet; Gunter Schmidtke; Marcus Groettrup; Cheetham, Michael E.; Jacqueline van der Spuy

    2012-01-01

    Mutations in AIPL1 cause the inherited blindness Leber congenital amaurosis (LCA). AIPL1 has previously been shown to interact with NUB1, which facilitates the proteasomal degradation of proteins modified with the ubiquitin-like protein FAT10. Here we report that AIPL1 binds non-covalently to free FAT10 and FAT10ylated proteins and can form a ternary complex with FAT10 and NUB1. In addition, AIPL1 antagonised the NUB1-mediated degradation of the model FAT10 conjugate, FAT10-DHFR, and pathogen...

  10. Genetic heterogeneity of butterfly-shaped pigment dystrophy of the fovea.

    OpenAIRE

    Lith-Verhoeven, J.J. van; Cremers, F.P.M.; Helm, L.J.M. van den; Hoyng, C.B.; Deutman, A F

    2003-01-01

    PURPOSE: Butterfly-shaped macular dystrophy (BSMD) has so far only been associated with mutations in the peripherin/RDS gene. The initial aim of our study was to investigate the peripherin/RDS gene as the causative gene in a family with BSMD. Subsequently the putative involvement of the ROM-1 gene, 4 genes expressed in cone photoreceptors, all known non-syndromic macular, retinal pigment epithelium and choroidal dystrophy loci, all known Leber congenital amaurosis loci and all known non-syndr...

  11. Disease: H00837 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available re than a dozen genes. Several have been demonstrated as potentially efficacious gene therapy targets. Nervo... (LCA15) TULP1 [HSA:7287] (LCA16) KCNJ13 [HSA:3769] [KO:K05006] Gene therapy ICD-10: H35.5 MeSH: D057130 OMI...) PMID:21705775 Liu MM, Tuo J, Chan CC Republished review: Gene therapy for ocular diseases. Postgrad Med J ...87:487-95 (2011) PMID:20399883 Cideciyan AV Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Prog Retin Eye Res 29:398-427 (2010) ...

  12. Reversão de amaurose por neuropatia óptica em orbitopatia de Graves após descompressão orbitária: relato de caso Reversal of blindness due to Graves' optic neuropathy after orbital decompression: case report

    Directory of Open Access Journals (Sweden)

    Valmor Rios Leme

    2003-12-01

    Full Text Available OBJETIVO: Descrever o caso de uma paciente portadora de orbitopatia de Graves com baixa visual no olho esquerdo há 9 meses e amaurose no direito há 20 dias secundária à neuropatia óptica. MÉTODOS: Foi realizada descompressão orbitária bilateral ínfero-medial por via transconjuntival. RESULTADOS: Após a cirurgia a paciente evoluiu lentamente com melhora progressiva da acuidade visual, obtendo 20/20 em ambos os olhos ao cabo de 10 meses. CONCLUSÕES: A descompressão orbitária é eficaz em restabelecer a visão em casos de amaurose por neuropatia óptica da orbitopatia de Graves com até 20 dias de instalação.PURPOSE: To describe a patient with Graves' orbitopathy who presented with loss of vision of the left eye for 9 months and amaurosis of the right eye for 20 days. METHODS: Bilateral inferomedial transnconjunctival orbital decompression was performed. RESULTS: After orbital decompression, vision slowly improved and ten months after the surgery the vision was normal in both eyes. CONCLUSIONS: Orbital decompression can reestablish optic nerve function at least 20 days after amaurosis.

  13. Radiologic diagnosis of Legg-Calve-Perthes disease

    International Nuclear Information System (INIS)

    In Legg-Calve-Perthes disease (LCPD), magnetic resonance imaging (MRI) and conventional radiography in two planes are considered the most important methods of investigation for early diagnosis and for assessment of the course of the disease. MRI can reveal the early marrow oedema, thus allowing early differential diagnosis against diseases that are similar in clinical appearance (coxitis fugax, epiphyseal dysplasia). The extent of the necrotica area within the epiphysis, the most important indicator of the prognosis of the disease and thus for the therapeutic management, can be assessed earlier and more reliably with MRI than with other techniques. The loss of containment can be visualized by MRI, because depiction of the cartilaginous structures is possible earlier than with conventional radiography. Staging of LCPD is also possible with MRI, especially in stages I and II. Radiography shows the reossification and the osseous remodelling of the epiphysis better. A disadvantage of MRI seems to be the occasional need for sedation or anaesthesia of the child to avoid motion artefacts. (orig.)

  14. Diurnal and twenty-four hour patterning of human diseases: acute and chronic common and uncommon medical conditions.

    Science.gov (United States)

    Smolensky, Michael H; Portaluppi, Francesco; Manfredini, Roberto; Hermida, Ramon C; Tiseo, Ruana; Sackett-Lundeen, Linda L; Haus, Erhard L

    2015-06-01

    The symptom intensity and mortality of human diseases, conditions, and syndromes exhibit diurnal or 24 h patterning, e.g., skin: atopic dermatitis, urticaria, psoriasis, and palmar hyperhidrosis; gastrointestinal: esophageal reflux, peptic ulcer (including perforation and hemorrhage), cyclic vomiting syndrome, biliary colic, hepatic variceal hemorrhage, and proctalgia fugax; infection: susceptibility, fever, and mortality; neural: frontal, parietal, temporal, and occipital lobe seizures, Parkinson's and Alzheimer's disease, hereditary progressive dystonia, and pain (cancer, post-surgical, diabetic neuropathic and foot ulcer, tooth caries, burning mouth and temporomandibular syndromes, fibromyalgia, sciatica, intervertebral vacuum phenomenon, multiple sclerosis muscle spasm, and migraine, tension, cluster, hypnic, and paroxysmal hemicranial headache); renal: colic and nocturnal enuresis and polyuria; ocular: bulbar conjunctival redness, keratoconjunctivitis sicca, intraocular pressure and anterior ischemic optic neuropathy, and recurrent corneal erosion syndrome; psychiatric/behavioral: major and seasonal affective depressive disorders, bipolar disorder, parasuicide and suicide, dementia-associated agitation, and addictive alcohol, tobacco, and heroin cravings and withdrawal phenomena; plus autoimmune and musculoskeletal: rheumatoid arthritis, osteoarthritis, axial spondylarthritis, gout, Sjögren's syndrome, and systemic lupus erythematosus. Knowledge of these and other 24 h patterns of human pathophysiology informs research of their underlying circadian and other endogenous mechanisms, external temporal triggers, and more effective patient care entailing clinical chronopreventive and chronotherapeutic strategies. PMID:25129839

  15. Investor Outlook: Significance of the Positive LCA2 Gene Therapy Phase III Results.

    Science.gov (United States)

    Schimmer, Joshua; Breazzano, Steven

    2015-12-01

    Spark Therapeutics recently reported positive phase III results for SPK-RPE65 targeting the treatment of visual impairment caused by RPE65 gene mutations (often referred to as Leber congenital amaurosis type 2, or LCA2, but may include other retinal disorders), marking an important inflection point for the field of gene therapy. The results highlight the ability to successfully design and execute a randomized trial of a gene therapy and also reinforce the potentially predictive nature of early preclinical and clinical data. The results are expected to pave the way for the first approved gene therapy product in the United States and should sustain investor interest and confidence in gene therapy for many approaches, including retina targeting and beyond. PMID:26684444

  16. Localized nasal cavity, sinus, and massive bilateral orbital involvement by human T cell leukemia virus 1 adult T cell lymphoma, with epidermal hypertrophy due to mite infestation

    Directory of Open Access Journals (Sweden)

    Albert S. Braverman

    2010-12-01

    Full Text Available HTLV1 adult T cell lymphoma occurs tends to be widely disseminated and aggressive, with only brief responses to chemotherapy. Aside from cervical adenopathy, involvement of head and neck structures is uncommon and orbital involvement rare. We report a case of nasal cavity HTLV lymphoma with massive bilateral orbital involvement and proptosis, resulting in complete left and partial right eye amaurosis. No other sites of disease were found. Response to chemotherapy was rapid and complete, with almost complete restoration of vision and oculo-motor function; the patient has remained in remission for one year. An associated problem was striking bilateral hypertrophic, hyperkeratotic eyelid and breast lesions due to mite infestation. 

  17. A Phe-rich region in short-wavelength sensitive opsins is responsible for their aggregation in the absence of 11-cis-retinal.

    Science.gov (United States)

    Zhang, Tao; Fu, Yingbin

    2013-08-01

    Human blue and mouse S-opsin are prone to aggregation in the absence of 11-cis-retinal, which underlie the rapid cone degeneration in human patients and animal models of Leber congenital amaurosis (LCA). By in silico analysis and domain swapping experiments, we show that a Phe-rich region in short-wavelength sensitive (SWS) opsins, but not in medium/long-wavelength sensitive opsins, is responsible for SWS opsin aggregation. Mutagenesis studies suggest that Phe residues in this region are critical in mediating protein aggregation. Fusing the Phe-rich region of SWS opsins to GFP causes the latter to aggregate. Our findings suggest that new therapeutics can be designed to disrupt the Phe-rich region in preventing cone degeneration due to S-opsin aggregation in LCA. PMID:23792161

  18. RPGR-containing protein complexes in syndromic and non-syndromic retinal degeneration due to ciliary dysfunction

    Indian Academy of Sciences (India)

    Carlos A. Murga-Zamalloa; Anand Swaroop; Hemant Khanna

    2009-12-01

    Dysfunction of primary cilia due to mutations in cilia-centrosomal proteins is associated with pleiotropic disorders. The primary (or sensory) cilium of photoreceptors mediates polarized trafficking of proteins for efficient phototransduction. Retinitis pigmentosa GTPase regulator (RPGR) is a cilia-centrosomal protein mutated in >70% of X-linked RP cases and 10%–20% of simplex RP males. Accumulating evidence indicates that RPGR may facilitate the orchestration of multiple ciliary protein complexes. Disruption of these complexes due to mutations in component proteins is an underlying cause of associated photoreceptor degeneration. Here, we highlight the recent developments in understanding the mechanism of cilia-dependent photoreceptor degeneration due to mutations in RPGR and RPGR-interacting proteins in severe genetic diseases, including retinitis pigmentosa, Leber congenital amaurosis (LCA), Joubert syndrome, and Senior–Loken syndrome, and explore the physiological relevance of photoreceptor ciliary protein complexes.

  19. Revisión bibliográfica sobre la influencia de la baja visión en el estado socioemocional y la calidad de vida de los pacientes mayores

    OpenAIRE

    García Manjarrés, Marta

    2014-01-01

    En esta revisión bibliográfica se objetiva la dificultad de establecer una definición universal para la baja visión a lo largo de la historia. Se puede apreciar cómo los conceptos y definiciones han ido modificándose y evolucionando con el tiempo. Sólo la ceguera total o amaurosis implica ausencia de visión. Pero la mayoría de las personas a las que llamamos comúnmente “ciegas” conservan restos visuales que pueden ser útiles en su vida diaria. Así, entre la ceguera y la visión ...

  20. Emergency placement of stent-graft for symptomatic acute carotid artery occlusion after endarterectomy.

    Science.gov (United States)

    Ko, Jun Kyeung; Choi, Chang Hwa; Lee, Sang Weon; Lee, Tae Hong

    2016-03-01

    A patient underwent a left-sided carotid endarterectomy (CEA) for an asymptomatic 80% carotid artery (CA) stenosis. There were no signs of intolerance during the carotid cross-clamping and an initially uneventful awakening was observed. However, in the third postoperative hour he experienced left amaurosis and dysarthria. An urgent MRI showed an occluded internal CA on the operated site without evidence of acute infarction. To recanalize the occluded internal CA and minimize leakage from the arteriotomy site, a self-expandable stent-graft was placed, covering the dissection and the distal atherosclerotic lesions. Complete recanalization of the left internal CA was achieved and the patient showed a dramatic improvement of his preoperative deficits. To our knowledge, this is the first case of stent-graft implantation for a symptomatic acute CA occlusion following CEA. Stent-graft placement should be considered as an alternative method of treatment for acute CA occlusion or dissection following CEA. PMID:25653229

  1. Bilateral posterior RION after concomitant radiochemotherapy with temozolomide in a patient with glioblastoma multiforme: a case report

    International Nuclear Information System (INIS)

    Radiation induced optic neuropathy (RION) is a rare but severe consequence of radiation therapy that is associated with adjuvant chemotherapy, specifically therapy with vincristine or nitrosoureas. However, there is very little evidence regarding the occurrence of RION after concomitant radiochemotherapy with temozolomide. The case of a 63 year old woman with glioblastoma multiforme and concomitant radiochemotherapy with temozolomide is described. Due to a slight depressive episode the patient also took hypericum perforatum. Five months after cessation of fractionated radiation and adjuvant chemotherapy with temozolomide (cumulative dose of 11040 mg) the patient developed bilateral amaurosis due to RION. Tumor regrowth was excluded by magnetic resonance imaging. After the application of gadolinium a pathognomonic contrast enhancement of both prechiasmatic optic nerves could be observed. In this patient, the occurrence of RION may have been the result of radiosensitization by temozolomide, which could have been strengthened by hypericin. Consequently, physicians should avoid a concomitant application of hypericum perforatum and radiochemotherapy

  2. Using Stem Cells to Model Diseases of the Outer Retina

    Directory of Open Access Journals (Sweden)

    Camille Yvon

    2015-01-01

    Full Text Available Retinal degeneration arises from the loss of photoreceptors or retinal pigment epithelium (RPE. It is one of the leading causes of irreversible blindness worldwide with limited effective treatment options. Generation of induced pluripotent stem cell (IPSC-derived retinal cells and tissues from individuals with retinal degeneration is a rapidly evolving technology that holds a great potential for its use in disease modelling. IPSCs provide an ideal platform to investigate normal and pathological retinogenesis, but also deliver a valuable source of retinal cell types for drug screening and cell therapy. In this review, we will provide some examples of the ways in which IPSCs have been used to model diseases of the outer retina including retinitis pigmentosa (RP, Usher syndrome (USH, Leber congenital amaurosis (LCA, gyrate atrophy (GA, juvenile neuronal ceroid lipofuscinosis (NCL, Best vitelliform macular dystrophy (BVMD and age related macular degeneration (AMD.

  3. Gene-Based Therapies for Leber Hereditary Optic Neuropathy. Hype or Hope?

    Science.gov (United States)

    Mackey, David A; Kearns, Lisa S; Hewitt, Alex W

    2016-01-01

    Leber hereditary optic neuropathy has now joined Leber congenital amaurosis in the list of genetic eye diseases undergoing gene therapy clinical trials. Although a dramatic response to treatment would be welcome, a minor improvement in vision is a major challenge in efficacy assessment, given this may occur spontaneously as part of the natural history of minor recovery in some patients. Thus, we must await the outcome of adequately powered clinical trials to know if the treatment is effective, particularly given the likely high cost of such therapeutic interventions in the future. We need global cooperation to ensure that the most suitable patients are enrolled in these trials and that support is provided for participants who need to travel from the Asia-Pacific region to Europe or North America if there are no local arms of these trials. PMID:27488066

  4. Genetics in Ophthalmology III – Posterior Segment Diseases

    Directory of Open Access Journals (Sweden)

    Canan Aslı Utine

    2012-10-01

    Full Text Available Genetic diseases are congenital or acquired hereditary diseases that result from structural/functional disorders of the human genome. Today, the genetic factors that play a role in many diseases are being highlighted with the rapid progress in the field of genetics science. It becomes increasingly important that physicians from all disciplines have knowledge about the basic principles of genetics, patterns of inheritance, etc., so that they can follow the new developments. In genetic eye diseases, ophthalmologists should know the basic clinical and recently rapidly developing genetic characteristics of these diseases in order to properly approach the diagnosis and treatment and to provide genetic counseling. In this paper, posterior segment eye diseases of genetic origin are reviewed, and retinoblastoma, mitochondrial diseases, retinal dysplasia, retinitis pigmentosa, choroideremia, gyrate atrophy, Alström disease, ocular albinism, optic nerve hypoplasia, anophthalmia/microphthalmia and Leber’s congenital amaurosis are covered. (Turk J Ophthalmol 2012; 42: 386-92

  5. Inherited retinal disorders in South Africa and the clinical impact of evolving technologies.

    Science.gov (United States)

    Roberts, L; Goliath, R; Rebello, G; Bardien, S; September, A V; Bartmann, L; Loubser, F; Greenberg, L J; Ramesar, R S

    2016-01-01

    Retinal degenerative disorders (RDDs) encompass a group of inherited diseases characterised by vision loss. The genetic and clinical complexity poses a challenge in unravelling the molecular genetic aetiology of this group of disorders. Furthermore, the population diversity in South Africa (SA) presents researchers with a particularly complicated task. Rapid advances in the development of cutting-edge technological platforms over the past two decades, however, have assisted in overcoming some of the challenges. The RDD research team has utilised these escalating technologies, which has facilitated a corresponding increase in molecular diagnoses. A biorepository has been established and comprises ~3 200 patient DNA samples archived with many forms of RDD (including retinitis pigmentosa, macular dystrophies, Stargardt disease, Leber congenital amaurosis, Usher syndrome and Bardet Biedl syndrome). A comprehensive review is presented of the SA journey spanning 25 years, into elucidating the molecular genetic basis of various forms of RDD in SA. PMID:27245521

  6. 11 Wild Silkworm Resources Distributed in Liaoning Province%分布在辽宁省的11种野蚕资源

    Institute of Scientific and Technical Information of China (English)

    杜占军; 杨桂梅; 陈凤林; 王建业; 仝振祥

    2011-01-01

    By means of field survey and consulting relevant materials, it is clear that except for tussah silkworm, there are 11 other wild silkworm species distributed in Liaoning province, namely, Antheraea yamamai, Dictyoploca japonica, Samia cynthia, Rhodinia fugax, Actias selene ningpoana, Erigyna pyretorum pyretorum, Samia cynthia ricina, Caligula boisduvalii fallax, Dictyoploca cachara, Rhodinia jankowskii, and Aglia tau amurensis, which belong to spinning insect from family Saturniidae. General information about these 11 wild silkworm species such as distribution, food plant, biological character and current situation of utilization was summarized, aiming to provide basic information for further research and protection of these wild species.%通过近几年在辽宁省各地实地考察和查阅相关文献资料,明确辽宁省分布的野蚕资源除柞蚕以外,还有天蚕、栗蚕、樗蚕、透目大蚕、柳蚕、樟蚕、蓖麻蚕、合目大蚕、胡桃大蚕、曲线透目大蚕、丁目大蚕等11种野蚕,这11种野蚕属大蚕蛾科(Satumiidae)的泌丝昆虫.概述11种野蚕在辽宁省的分布、取食植物、生物学特性及开发利用现状,为野蚕资源的保护、研究和开发利用提供基础信息.

  7. Pathological, clinical and biochemical investigation of naturally occurring pregnancy toxemia of sheep

    Directory of Open Access Journals (Sweden)

    Kabakci N.

    2003-01-01

    Full Text Available A sick ewe in late pregnancy presented with clinical incoordination lipping, amaurosis, head tilt gait and nervous symptoms such as circling movements. A smell of ketones on the breath was detected. The sick animal died during clinical examination and, together with three more dead animals belonging to the same flock, was submitted to the laboratory for necropsy. The uteri of all pregnant animals contained late-term twin fetuses. The most prominent lesion was extensive fatty infiltration of the liver. Massive lipidosis and lipid vacuoles were seen in sections of the livers. In three brains, there was prominent vacuolation in the white matter. Urine analysis revealed ketonuria in most of the suspected sheep from the same flock. Serum glucose, cholesterol, high density lipoprotein cholesterol, and blood urea nitrogen concentrations were lower (p£0.05 and serum triglycerides aspartate aminotransferase and alanine aminotransferase activities were higher (p£0.05 in these sheep than in the controls. After a change of diet and treatment, with glucose and dexamethasone serum glucose levels significantly increased (p£0.001 and urine ketone bodies decreased but the other biocemical differences remained.

  8. Crystal structure of native RPE65, the retinoid isomerase of the visual cycle

    Energy Technology Data Exchange (ETDEWEB)

    Kiser, Philip D.; Golczak, Marcin; Lodowski, David T.; Chance, Mark R.; Palczewski, Krzysztof; (WRU-MED)

    2009-12-01

    Vertebrate vision is maintained by the retinoid (visual) cycle, a complex enzymatic pathway that operates in the retina to regenerate the visual chromophore, 11-cis-retinal. A key enzyme in this pathway is the microsomal membrane protein RPE65. This enzyme catalyzes the conversion of all-trans-retinyl esters to 11-cis-retinol in the retinal pigment epithelium (RPE). Mutations in RPE65 are known to be responsible for a subset of cases of the most common form of childhood blindness, Leber congenital amaurosis (LCA). Although retinoid isomerase activity has been attributed to RPE65, its catalytic mechanism remains a matter of debate. Also, the manner in which RPE65 binds to membranes and extracts retinoid substrates is unclear. To gain insight into these questions, we determined the crystal structure of native bovine RPE65 at 2.14-{angstrom} resolution. The structural, biophysical, and biochemical data presented here provide the framework needed for an in-depth understanding of the mechanism of catalytic isomerization and membrane association, in addition to the role mutations that cause LCA have in disrupting protein function.

  9. The retinal ciliopathies.

    Science.gov (United States)

    Adams, N A; Awadein, Ahmed; Toma, Hassanain S

    2007-09-01

    While the functions of many of the proteins located in or associated with the photoreceptor cilia are poorly understood, disruption of the function of these proteins may result in a wide variety of phenotypes ranging from isolated retinal degeneration to more pleiotropic phenotypes. Systemic findings include neurosensory hearing loss, developmental delay, situs-inversus, infertility, disorders of limb and digit development, obesity, kidney disease, liver disease, and respiratory disease. The concept of "retinal ciliopathies" brings to attention the importance of further molecular analysis of this organelle as well as provides a potential common target for therapies for these disorders. The retinal ciliopathies include retinitis pigmentosa, macular degeneration, cone-dystrophy, cone-rod dystrophy, Leber congenital amaurosis, as well as retinal degenerations associated with Usher syndrome, primary ciliary dyskinesia, Senior-Loken syndrome, Joubert syndrome, Bardet-Biedl syndrome, Laurence-Moon syndrome, McKusick-Kaufman syndrome, and Biemond syndrome. Mutations for these disorders have been found in retinitis pigmentosa-1 (RP1), retinitis pigmentosa GTPase regulator (RPGR), retinitis pigmentosa GTPase regulator interacting protein (RPGR-IP), as well as the Usher, Bardet-Biedl, and nephronophthisis genes. Other systemic disorders associated with retinal degenerations that may also involve ciliary abnormalities include: Alstrom, Edwards-Sethi, Ellis-van Creveld, Jeune, Meckel-Gruber, Orofaciodigital Type 9, and Gurrieri syndromes. Understanding these conditions as ciliopathies may help the ophthalmologist to recognize associations between seemingly unrelated diseases and have a high degree of suspicion that a systemic finding may be present. PMID:17896309

  10. The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway.

    Directory of Open Access Journals (Sweden)

    John S Bett

    Full Text Available Mutations in AIPL1 cause the inherited blindness Leber congenital amaurosis (LCA. AIPL1 has previously been shown to interact with NUB1, which facilitates the proteasomal degradation of proteins modified with the ubiquitin-like protein FAT10. Here we report that AIPL1 binds non-covalently to free FAT10 and FAT10ylated proteins and can form a ternary complex with FAT10 and NUB1. In addition, AIPL1 antagonised the NUB1-mediated degradation of the model FAT10 conjugate, FAT10-DHFR, and pathogenic mutations of AIPL1 were defective in inhibiting this degradation. While all AIPL1 mutants tested still bound FAT10-DHFR, there was a close correlation between the ability of the mutants to interact with NUB1 and their ability to prevent NUB1-mediated degradation. Interestingly, AIPL1 also co-immunoprecipitated the E1 activating enzyme for FAT10, UBA6, suggesting AIPL1 may have a role in directly regulating the FAT10 conjugation machinery. These studies are the first to implicate FAT10 in retinal cell biology and LCA pathogenesis, and reveal a new role of AIPL1 in regulating the FAT10 pathway.

  11. Identification and Correction of Mechanisms Underlying Inherited Blindness in Human iPSC-Derived Optic Cups.

    Science.gov (United States)

    Parfitt, David A; Lane, Amelia; Ramsden, Conor M; Carr, Amanda-Jayne F; Munro, Peter M; Jovanovic, Katarina; Schwarz, Nele; Kanuga, Naheed; Muthiah, Manickam N; Hull, Sarah; Gallo, Jean-Marc; da Cruz, Lyndon; Moore, Anthony T; Hardcastle, Alison J; Coffey, Peter J; Cheetham, Michael E

    2016-06-01

    Leber congenital amaurosis (LCA) is an inherited retinal dystrophy that causes childhood blindness. Photoreceptors are especially sensitive to an intronic mutation in the cilia-related gene CEP290, which causes missplicing and premature termination, but the basis of this sensitivity is unclear. Here, we generated differentiated photoreceptors in three-dimensional optic cups and retinal pigment epithelium (RPE) from iPSCs with this common CEP290 mutation to investigate disease mechanisms and evaluate candidate therapies. iPSCs differentiated normally into RPE and optic cups, despite abnormal CEP290 splicing and cilia defects. The highest levels of aberrant splicing and cilia defects were observed in optic cups, explaining the retinal-specific manifestation of this CEP290 mutation. Treating optic cups with an antisense morpholino effectively blocked aberrant splicing and restored expression of full-length CEP290, restoring normal cilia-based protein trafficking. These results provide a mechanistic understanding of the retina-specific phenotypes in CEP290 LCA patients and potential strategies for therapeutic intervention. PMID:27151457

  12. Involvement of Endoplasmic Reticulum Stress in TULP1 Induced Retinal Degeneration.

    Directory of Open Access Journals (Sweden)

    Glenn P Lobo

    Full Text Available Inherited retinal disorders (IRDs result in severe visual impairments in children and adults. A challenge in the field of retinal degenerations is identifying mechanisms of photoreceptor cell death related to specific genetic mutations. Mutations in the gene TULP1 have been associated with two forms of IRDs, early-onset retinitis pigmentosa (RP and Leber congenital amaurosis (LCA. TULP1 is a cytoplasmic, membrane-associated protein shown to be involved in transportation of newly synthesized proteins destined for the outer segment compartment of photoreceptor cells; however, how mutant TULP1 causes cell death is not understood. In this study, we provide evidence that common missense mutations in TULP1 express as misfolded protein products that accumulate within the endoplasmic reticulum (ER causing prolonged ER stress. In an effort to maintain protein homeostasis, photoreceptor cells then activate the unfolded protein response (UPR complex. Our results indicate that the two major apoptotic arms of the UPR pathway, PERK and IRE1, are activated. Additionally, we show that retinas expressing mutant TULP1 significantly upregulate the expression of CHOP, a UPR signaling protein promoting apoptosis, and undergo photoreceptor cell death. Our study demonstrates that the ER-UPR, a known mechanism of apoptosis secondary to an overwhelming accumulation of misfolded protein, is involved in photoreceptor degeneration caused by missense mutations in TULP1. These observations suggest that modulating the UPR pathways might be a strategy for therapeutic intervention.

  13. Directed evolution of novel adeno-associated viruses for therapeutic gene delivery.

    Science.gov (United States)

    Bartel, M A; Weinstein, J R; Schaffer, D V

    2012-06-01

    Gene therapy vectors based on adeno-associated virus (AAV) are currently in clinical trials for numerous disease targets, such as muscular dystrophy, hemophilia, Parkinson's disease, Leber's congenital amaurosis and macular degeneration. Despite its considerable promise and emerging clinical success, several challenges impede the broader implementation of AAV gene therapy, including the prevalence of neutralizing antibodies in the human population, low transduction of a number of therapeutically relevant cell and tissue types, an inability to overcome physical and cellular barriers in vivo and a relatively limited carrying capacity. These challenges arise as the demands we place on AAV vectors are often different from or even at odds with the properties nature bestowed on their parent viruses. Viral-directed evolution-the iterative generation of large, diverse libraries of viral mutants and selection for variants with specific properties of interest-offers an approach to address these problems. Here we outline progress in creating novel classes of AAV variant libraries and highlight the successful isolation of variants with novel and advantageous in vitro and in vivo gene delivery properties. PMID:22402323

  14. RPE65 gene: multiplex PCR and mutation screening in patients from India with retinal degenerative diseases

    Indian Academy of Sciences (India)

    Biju Joseph; Anuradha Srinivasan; Nagasamy Soumittra; Authiappan Vidhya; Nitin Shridhara Shetty; Satagopan Uthra; Govindasamy Kumaramanickavel

    2002-04-01

    We used multiplex PCR followed by sequencing to screen for mutations in the 14 exons of the RPE65 gene in early-childhood-onset autosomal recessive retinitis pigmentosa (arRP) and Leber’s congenital amaurosis (LCA) patients. The RPE65 protein is believed to play an important role in the metabolism of vitamin A in the visual cycle and mutations identified in the gene could have implications for vitamin A-based therapeutic intervention. We were able to identify a homozygous mutation (AAT → AAG) in exon 9 in an arRP patient and a heterozygous missense transversion (AAT → AAG) also in exon 9 of an LCA patient. We also identified a polymorphism in exon 10 (GAG → GAA) in an arRP as well as an LCA patient. Mutation screening would be greatly facilitated by multiplex PCR which could cut down costs, labour and time involved. The nucleotide changes observed in this study could be de novo. Though a larger study has been undertaken, from the preliminary results it appears that in India the RPE65 gene seems to be less involved in causation of LCA.

  15. Homozygous missense variant in the human CNGA3 channel causes cone-rod dystrophy.

    Science.gov (United States)

    Shaikh, Rehan S; Reuter, Peggy; Sisk, Robert A; Kausar, Tasleem; Shahzad, Mohsin; Maqsood, Muhammad I; Yousif, Ateeq; Ali, Muhammad; Riazuddin, Saima; Wissinger, Bernd; Ahmed, Zubair M

    2015-04-01

    We assessed a large consanguineous Pakistani family (PKAB157) segregating early onset low vision problems. Funduscopic and electroretinographic evaluation of affected individuals revealed juvenile cone-rod dystrophy (CRD) with maculopathy. Other clinical symptoms included loss of color discrimination, photophobia and nystagmus. Whole-exome sequencing, segregation and haplotype analyses demonstrated that a transition variant (c.955T>C; p.(Cys319Arg)) in CNGA3 co-segregated with the CRD phenotype in family PKAB157. The ability of CNGA3 channel to influx calcium in response to agonist, when expressed either alone or together with the wild-type CNGB3 subunit in HEK293 cells, was completely abolished due to p.Cys319Arg variant. Western blotting and immunolocalization studies suggest that a decreased channel density in the HEK293 cell membrane due to impaired folding and/or trafficking of the CNGA3 protein is the main pathogenic effect of the p.Cys319Arg variant. Mutant alleles of the human cone photoreceptor cyclic nucleotide-gated channel (CNGA3) are frequently associated with achromatopsia. In rare cases, variants in CNGA3 are also associated with cone dystrophy, Leber's congenital amaurosis and oligo cone trichromacy. The identification of predicted p.(Cys319Arg) missense variant in CNGA3 expands the repertoire of the known genetic causes of CRD and phenotypic spectrum of CNGA3 alleles. PMID:25052312

  16. The ADAMTS18 gene is responsible for autosomal recessive early onset severe retinal dystrophy

    Directory of Open Access Journals (Sweden)

    Peluso Ivana

    2013-01-01

    Full Text Available Abstract Background Inherited retinal dystrophies, including Retinitis Pigmentosa and Leber Congenital Amaurosis among others, are a group of genetically heterogeneous disorders that lead to variable degrees of visual deficits. They can be caused by mutations in over 100 genes and there is evidence for the presence of as yet unidentified genes in a significant proportion of patients. We aimed at identifying a novel gene for an autosomal recessive form of early onset severe retinal dystrophy in a patient carrying no previously described mutations in known genes. Methods An integrated strategy including homozygosity mapping and whole exome sequencing was used to identify the responsible mutation. Functional tests were performed in the medaka fish (Oryzias latipes model organism to gain further insight into the pathogenic role of the ADAMTS18 gene in eye and central nervous system (CNS dysfunction. Results This study identified, in the analyzed patient, a homozygous missense mutation in the ADAMTS18 gene, which was recently linked to Knobloch syndrome, a rare developmental disorder that affects the eye and the occipital skull. In vivo gene knockdown performed in medaka fish confirmed both that the mutation has a pathogenic role and that the inactivation of this gene has a deleterious effect on photoreceptor cell function. Conclusion This study reveals that mutations in the ADAMTS18 gene can cause a broad phenotypic spectrum of eye disorders and contribute to shed further light on the complexity of retinal diseases.

  17. Insights gained from gene therapy in animal models of retGC1 deficiency

    Directory of Open Access Journals (Sweden)

    Shannon Elizabeth Boye

    2014-05-01

    Full Text Available Vertebrate species possess two retinal guanylate cyclases (retGC1 and retGC2 and at least two guanylate cyclase activating proteins (GCAPs, GCAP1 and GCAP2. GCAPs function as Ca2+ sensors that regulate the activity of guanylate cyclases. Together, these proteins regulate cGMP and Ca2+ levels within the outer segments of rod and cone photoreceptors. Mutations in GUCY2D, the gene that encodes retGC1, are a leading cause of the most severe form of early onset retinal dystrophy, Leber congenital amaurosis (LCA1. These mutations, which reduce or abolish the ability of retGC1 to replenish cGMP in photoreceptors, are thought to lead to the biochemical equivalent of chronic light exposure in these cells. In spite of this, the majority of LCA1 patients retain normal photoreceptor laminar architecture aside from foveal cone outer segment abnormalities, suggesting they may be good candidates for gene replacement therapy. Work began in the 1980s to characterize multiple animal models of retGC1 deficiency. Thirty four years later, all models have been used in proof of concept gene replacement studies towards the goal of developing a therapy to treat GUCY2D-LCA1. Here we use the results of these studies as well as those of recent clinical studies to address specific questions relating to clinical application of a gene therapy for treatment of LCA1.

  18. A gene for autosomal dominant progressive cone dystrophy (CORD5) maps to chromosome 17p12-p13

    Energy Technology Data Exchange (ETDEWEB)

    Balciuniene, J.; Holmgren, G.; Forsman, K. [University Hospital, Umea (Sweden)] [and others

    1995-11-20

    Inherited retinal dystrophy is a common cause of visual impairment. Cone dystrophy affects the cone function and is manifested as progressive loss of the central vision, defective color vision, and photophobia. Linkage was demonstrated between progressive cone dystrophy (CORD5) and genetic markers on chromosome 17p12-p13 in a five-generation family. Multipoint analysis gave a maximum lod score of 7.72 at the marker D17S938. Recombinant haplotypes in the family suggest that the cone dystrophy locus is located in a 25-cM interval between the markers D17S926/D17S849 and D17S804/D17S945. Furthermore, one recombination was detected between the disease locus and a microsatellite marker in the candidate gene RCV1, encoding the retinal protein recoverin. Two additional candidate genes encoding retinal guanylate cyclase (GUC2D) and pigment epithelium-derived factor (PEDF) are located at 17p13.1. Moreover, loci for retinitis pigmentosa and Leber congenital amaurosis have been mapped to the same region. Identification of the cone dystrophy locus may be of importance not only for identifying functional genes in the cone system, but also for identifying genes for other retinal disorders. 34 refs., 3 figs., 2 tabs.

  19. Novel mutations in two Saudi patients with congenital retinal dystrophy

    Directory of Open Access Journals (Sweden)

    Leen Abu Safieh

    2016-01-01

    Full Text Available To report novel mutations in two Saudi children with clinical features of Leber congenital amaurosis (LCA and Alström syndrome. Case reports. Case 1 was a child with phenotypic features of LCA including oculodigital sign, bilateral enophthalmos, nystagmus, pale disc, and retinal changes. Direct sequencing of the coding sequence of GUCY2D revealed a missense mutation affecting highly conserved position (c. 743C > T; p.S248 L. Case 2 describes a girl with marked nystagmus, photophobia, and retinal changes in both eyes with short and stubby fingers tapering at the distal phalanges. The electroretinograms were nonrecordable in each eye. She had a hearing aid in the left ear, mid-facial hypoplasia, bilateral enophthalmos, and insulin dependent diabetes. Mutation screening of candidates genes revealed a pathogenic mutation in ALMS1 gene (c. 8441C > A, p.S2814*. Two novel mutations causing phenotypic LCA and Alström syndrome in Saudi patients from consanguineous families expand the genotypic spectrum of congenital retinal dystrophies

  20. Synaptogenesis and outer segment formation are perturbed in the neural retina of Crx mutant mice

    Directory of Open Access Journals (Sweden)

    Raviola Elio

    2005-01-01

    Full Text Available Abstract Background In Leber's congenital amaurosis (LCA, affected individuals are blind, or nearly so, from birth. This early onset suggests abnormal development of the neural retina. Mutations in genes that affect the development and/or function of photoreceptor cells have been found to be responsible in some families. These examples include mutations in the photoreceptor transcription factor, Crx. Results A Crx mutant strain of mice was created to serve as a model for LCA and to provide more insight into Crx's function. In this study, an ultrastructural analysis of the developing retina in Crx mutant mice was performed. Outer segment morphogenesis was found to be blocked at the elongation stage, leading to a failure in production of the phototransduction apparatus. Further, Crx-/- photoreceptors demonstrated severely abnormal synaptic endings in the outer plexiform layer. Conclusions This is the first report of a synaptogenesis defect in an animal model for LCA. These data confirm the essential role this gene plays in multiple aspects of photoreceptor development and extend our understanding of the basic pathology of LCA.

  1. RE-EDUCATIVE METHOD IN THE PROCESS OF MINIMIZING OF AUTOAGRESIVE WAYS OF BEHAVIOR

    Directory of Open Access Journals (Sweden)

    Nenad GLUMBIC

    1999-05-01

    Full Text Available Autoagressive behavior is a relatively frequent symptom of mental disturbances and behavior disturbances which are the subject of professional engagement of clinically oriented defectologists. In the process of rehabilitation numerous methods are used, from behavioral to psychopharmacological ones by which the above mentioned problems are eliminated of softened.The paper deals with four children with different diagnosis (autism, disintegrative psychosis, Patau syndrome and amaurosis that have the same common denominator-mental retardation and autoagression.We have tried to point out-by the description of a study case as well as the ways od work with these children-an application possibly of the particular methods of general and special re-education of psychomotorics in the process of autoagressive ways of behavior minimizing.The paper gives the autor’s notion of indications for re-educative method application with in the multihandicapped children population. Defectological treatment discovers new forms of existence in the existential field, not only to the retarded child but also to the very therapist. Epistemological consequences of the mentioned transfer are given in details in the paper.

  2. C2 Domains as Protein-Protein Interaction Modules in the Ciliary Transition Zone

    Directory of Open Access Journals (Sweden)

    Kim Remans

    2014-07-01

    Full Text Available RPGR-interacting protein 1 (RPGRIP1 is mutated in the eye disease Leber congenital amaurosis (LCA and its structural homolog, RPGRIP1-like (RPGRIP1L, is mutated in many different ciliopathies. Both are multidomain proteins that are predicted to interact with retinitis pigmentosa G-protein regulator (RPGR. RPGR is mutated in X-linked retinitis pigmentosa and is located in photoreceptors and primary cilia. We solved the crystal structure of the complex between the RPGR-interacting domain (RID of RPGRIP1 and RPGR and demonstrate that RPGRIP1L binds to RPGR similarly. RPGRIP1 binding to RPGR affects the interaction with PDEδ, the cargo shuttling factor for prenylated ciliary proteins. RPGRIP1-RID is a C2 domain with a canonical β sandwich structure that does not bind Ca2+ and/or phospholipids and thus constitutes a unique type of protein-protein interaction module. Judging from the large number of C2 domains in most of the ciliary transition zone proteins identified thus far, the structure presented here seems to constitute a cilia-specific module that is present in multiprotein transition zone complexes.

  3. Adeno-Associated Virus-Mediated Gene Transfer to Renal Tubule Cells via a Retrograde Ureteral Approach

    Directory of Open Access Journals (Sweden)

    Daniel C. Chung

    2011-11-01

    Full Text Available Background/Aims: Gene therapy involves delivery of exogenous DNA to provide a therapeutic protein. Ideally, a gene therapy vector should be non-toxic, non-immunogenic, easy to produce, and efficient in protecting and delivering DNA into target cells. Methods: Adeno-associated virus (AAV offers these advantages and few, if any, disadvantages, and over 100 isolates exist. We previously showed that AAV-mediated gene therapy can be used to restore vision to patients with Leber’s congenital amaurosis, a disease of childhood blindness. Results: Here we show that novel recombinant AAV2/8 and AAV2/9 transduce kidney tubule cells with high efficiency both in vitroin cell culture and in vivoin mice. In addition, we adapted and modified a retrograde approach to allow for optimal transgene delivery to renal tubular cells that further minimizes the risk of an immunogenic reaction. Conclusions: We believe that recombinant AAV2, especially AAV2/8, gene delivery to renal tubule cells via a retrograde approach represents a viable method for gene therapy for a multitude of renal disorders ranging from autosomal dominant polycystic kidney disease to acute kidney injury.

  4. The soil seed bank characteristics in cropland under different conservation tillage and fertilization regimes in Loess Hill and Gully Region%陕北黄土丘陵沟壑区水土保持耕作及施肥下农田土壤种子库特征

    Institute of Scientific and Technical Information of China (English)

    黄茂林; 梁银丽; 周茂娟; 韦泽秀; 吴燕

    2009-01-01

    To better understand the mechanism of weed occurrence and suppression effect of crops on weeds, we conducted a 4-year field experiment in 4 crops under different tillage and fertilization regimes in Ansai, Shaanxi, China. The species composition, seed density, diversity and the similarity were measured in soil seed bank of soybean (Glycine max), corn (Zea mays), Red Bean (Semen Phaseoli ) and potato (Solanum tuberosum). The tillage and fertilization treatments in each crop included till-chemical fertilizer (CF), till-organic manure (CM), till no fertilizer (CN), no-till chemical fertilizer (NF), no-till-organic manure (NM), and no-till-no fertilizer (NN). The results showed that: (1) There were 12 weed species in 1965 seedlings from 24 soil samples in 4 crops. These species belonged to 7 families and 12 genuses and 94% of them were annual weeds. Bangtou grass (fugax nees ex steud), amaranth (Acalypha australis), large crabgrass (Digitaria sanguinalis) and Poa(Poa sphondylodes)were the dominant species and accounted for 87%;(2) In 0-20cm soil of different treatments, weed density ranged from (282.9 ± 63) to (7482.5 ±1078.3) seeds · m-2. There were significant differences (P potato plot > soybean plot > corn plot among 4 crops, tillage plot > no-tillage plot between 2 tillage treatments, and organic fertilizer plot > Fertilizer plot > no fertilizer plot among fertilization treatments;(3) Soil seed bank had the highest weed density in NM Red Bean and the lowest density in NN corn. The rich index was the highest (2.30) in CF soybean and the lowest (0.29) in NN Red Bean. The diversity index was the highest in NN soybean (5.56) and the lowest in CF Red bean (0.45). The ecological advantage of NF corn was the highest (1.35) and that of CF soybean was the lowest (0.17). Among the fertilization treatments, the similar coefficient of soil seed bank ranged from 0 to 0.63 in tilled system and from 0.67 to 0.92 in no-till system. As a result, corn and soybean were optimal

  5. Distilling a Visual Network of Retinitis Pigmentosa Gene-Protein Interactions to Uncover New Disease Candidates.

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    Daniel Boloc

    Full Text Available Retinitis pigmentosa (RP is a highly heterogeneous genetic visual disorder with more than 70 known causative genes, some of them shared with other non-syndromic retinal dystrophies (e.g. Leber congenital amaurosis, LCA. The identification of RP genes has increased steadily during the last decade, and the 30% of the cases that still remain unassigned will soon decrease after the advent of exome/genome sequencing. A considerable amount of genetic and functional data on single RD genes and mutations has been gathered, but a comprehensive view of the RP genes and their interacting partners is still very fragmentary. This is the main gap that needs to be filled in order to understand how mutations relate to progressive blinding disorders and devise effective therapies.We have built an RP-specific network (RPGeNet by merging data from different sources: high-throughput data from BioGRID and STRING databases, manually curated data for interactions retrieved from iHOP, as well as interactions filtered out by syntactical parsing from up-to-date abstracts and full-text papers related to the RP research field. The paths emerging when known RP genes were used as baits over the whole interactome have been analysed, and the minimal number of connections among the RP genes and their close neighbors were distilled in order to simplify the search space.In contrast to the analysis of single isolated genes, finding the networks linking disease genes renders powerful etiopathological insights. We here provide an interactive interface, RPGeNet, for the molecular biologist to explore the network centered on the non-syndromic and syndromic RP and LCA causative genes. By integrating tissue-specific expression levels and phenotypic data on top of that network, a more comprehensive biological view will highlight key molecular players of retinal degeneration and unveil new RP disease candidates.

  6. Lecithin:Retinol Acyltransferase: A Key Enzyme Involved in the Retinoid (visual) Cycle.

    Science.gov (United States)

    Sears, Avery E; Palczewski, Krzysztof

    2016-06-01

    Lecithin:retinol acyltransferase (LRAT) catalyzes the acyl transfer from the sn-1 position of phosphatidylcholine (PC) to all-trans-retinol, creating fatty acid retinyl esters (palmitoyl, stearoyl, and some unsaturated derivatives). In the eye, these retinyl esters are substrates for the 65 kDa retinoid isomerase (RPE65). LRAT is well characterized biochemically, and recent structural data from closely related family members of the NlpC/P60 superfamily and a chimeric protein have established its catalytic mechanism. Mutations in the LRAT gene are responsible for approximately 1% of reported cases of Leber congenital amaurosis (LCA). Lack of functional LRAT, expressed in the retinal pigmented epithelium (RPE), results in loss of the visual chromophore and photoreceptor degeneration. LCA is a rare hereditary retinal dystrophy with an early onset associated with mutations in one of 21 known genes. Protocols have been devised to identify therapeutics that compensate for mutations in RPE65, also associated with LCA. The same protocols can be adapted to combat dystrophies associated with LRAT. Improvement in the visual function of clinical recipients of therapy with recombinant adeno-associated virus (rAAV) vectors incorporating the RPE65 gene provides a proof of concept for LRAT, which functions in the same cell type and metabolic pathway as RPE65. In parallel, a clinical trial that employs oral 9-cis-retinyl acetate to replace the missing chromophore in RPE65 and LRAT causative disease has proven to be effective and free of adverse effects. This article summarizes the biochemistry of LRAT and examines chromophore replacement as a treatment for LCA caused by LRAT mutations. PMID:27183166

  7. Neurocisticercose e síndrome de lennox-gastaut: relato de caso Neurocysticercosis and Lennox-Gastaut syndrome: case report

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    SVETLANA AGAPEJEV

    2000-06-01

    Full Text Available Relata-se o caso de uma menina que, aos 2 anos de idade, apresentou a forma epiléptica, hidrocefálica e encefalítica da neurocisticercose, diagnosticada por exame do líquido cefalorraqueano e tomografia computadorizada de crânio, evolução com crises polimórficas, episódios de descompensação da hipertensão intracraniana por obstrução do sistema de derivação ventriculoperitoneal, retardo no desenvolvimento neuropsicomotor e cegueira até que, aos 10 anos de idade, foi diagnosticada síndrome de Lennox-Gastaut. Atualmente, a paciente tem 16 anos, apresenta sequelas neurológicas e crises parciais complexas com automatismos, parcialmente controladas com o uso de clobazan e oxcarbazepina. A primeira associação de neurocisticercose e síndrome de Lennox-Gastaut foi descrita em 1973, por Frochtengarten & Scarante, em uma menina com quadro clínico semelhante ao do caso relatado.Report of a girl with the epileptic, hydrocephalic and encephalitic form of neurocysticercosis, diagnosed by cerebrospinal flui and computed tomography exams, during her second year of life and an evolution with multiple types of seizures, prolonged periods of intracranial hypertension due to obstruction in the ventriculoperitoneal shunt, psicomotor regression and blindness until she was 10 years old, when the Lennox-Gastaut syndrome was diagnosed. Nowadays the patient is 16 years old and presents complex partial seizures with automatism not completely controlled with clobazan and oxcarbazepine, associated to left spastic hemiparesis, universal hyperreflexia, psychomotor agitation, self-mutilation, amaurosis and severe mental retardation. The association between neurocysticercosis and Lennox-Gastaut syndrome was first described in 1973 by Frochtengarten & Scarante in a Brazilian girl with a similar clinical picture.

  8. Atypical clinical presentation and long-term survival in a patient with optic nerve medulloepithelioma: a case report

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    Pastora-Salvador Natalia

    2012-05-01

    Full Text Available Abstract Introduction Medulloepithelioma is a rare congenital tumor of the primitive medullary neuroepithelium. A significant proportion of patients with medulloepithelioma arising from the optic nerve die from intracranial spread or cerebral metastasis. Because it has no known distinct clinical features and because of its low frequency, this tumor presents within the first two to six years of life and is usually misdiagnosed clinically as a different type of optic nerve tumor. Here, we describe a new and atypical case of medulloepithelioma of the optic nerve in a 12-year-old boy. To the best of our knowledge, he is the oldest reported patient to present with this disease and, now as an adult, has the longest documented period of disease-free survival. Case presentation A 12-year-old Caucasian boy with headache and unilateral amaurosis was referred for a presumed optic nerve glioma to our hospital. A computed tomography scan showed optic nerve enlargement, and fundoscopy showed a whitish mass at the optic disc. Our patient had been followed at his local hospital for four years for an 'optic disc cyst' with no change or progression. He experienced mild progressive visual impairment during that period. He was admitted for resection, and a histopathological analysis revealed a medulloepithelioma of the optic nerve. Supplemental orbital radiotherapy was performed. He remained disease-free for 25 years. Conclusions Medulloepithelioma of the optic nerve can clinically mimic more common pediatric tumors, such as optic glioma, meningioma, or retinoblastoma. Thus, medulloepithelioma should be included in the differential diagnoses of pediatric optic nerve lesions. Fundoscopy in these patients may provide relevant information for diagnosis. Anterior optic nerve medulloepitheliomas may behave differently from and have a better prognosis than medulloepitheliomas that have a more posterior location. Our case report illustrates that long-term survival can be

  9. Noninvasive, in vivo assessment of mouse retinal structure using optical coherence tomography.

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    M Dominik Fischer

    Full Text Available BACKGROUND: Optical coherence tomography (OCT is a novel method of retinal in vivo imaging. In this study, we assessed the potential of OCT to yield histology-analogue sections in mouse models of retinal degeneration. METHODOLOGY/PRINCIPAL FINDINGS: We achieved to adapt a commercial 3(rd generation OCT system to obtain and quantify high-resolution morphological sections of the mouse retina which so far required in vitro histology. OCT and histology were compared in models with developmental defects, light damage, and inherited retinal degenerations. In conditional knockout mice deficient in retinal retinoblastoma protein Rb, the gradient of Cre expression from center to periphery, leading to a gradual reduction of retinal thickness, was clearly visible and well topographically quantifiable. In Nrl knockout mice, the layer involvement in the formation of rosette-like structures was similarly clear as in histology. OCT examination of focal light damage, well demarcated by the autofluorescence pattern, revealed a practically complete loss of photoreceptors with preservation of inner retinal layers, but also more subtle changes like edema formation. In Crb1 knockout mice (a model for Leber's congenital amaurosis, retinal vessels slipping through the outer nuclear layer towards the retinal pigment epithelium (RPE due to the lack of adhesion in the subapical region of the photoreceptor inner segments could be well identified. CONCLUSIONS/SIGNIFICANCE: We found that with the OCT we were able to detect and analyze a wide range of mouse retinal pathology, and the results compared well to histological sections. In addition, the technique allows to follow individual animals over time, thereby reducing the numbers of study animals needed, and to assess dynamic processes like edema formation. The results clearly indicate that OCT has the potential to revolutionize the future design of respective short- and long-term studies, as well as the preclinical

  10. Bicarbonate and Ca(2+) Sensing Modulators Activate Photoreceptor ROS-GC1 Synergistically.

    Science.gov (United States)

    Duda, Teresa; Pertzev, Alexandre; Makino, Clint L; Sharma, Rameshwar K

    2016-01-01

    Photoreceptor ROS-GC1, a prototype subfamily member of the membrane guanylate cyclase family, is a central component of phototransduction. It is a single transmembrane-spanning protein, composed of modular blocks. In rods, guanylate cyclase activating proteins (GCAPs) 1 and 2 bind to its juxtamembrane domain (JMD) and the C-terminal extension, respectively, to accelerate cyclic GMP synthesis when Ca(2+) levels are low. In cones, the additional expression of the Ca(2+)-dependent guanylate cyclase activating protein (CD-GCAP) S100B which binds to its C-terminal extension, supports acceleration of cyclic GMP synthesis at high Ca(2+) levels. Independent of Ca(2+), ROS-GC1 activity is also stimulated directly by bicarbonate binding to the core catalytic domain (CCD). Several enticing molecular features of this transduction system are revealed in the present study. In combination, bicarbonate and Ca(2+)-dependent modulators raised maximal ROS-GC activity to levels that exceeded the sum of their individual effects. The F(514)S mutation in ROS-GC1 that causes blindness in type 1 Leber's congenital amaurosis (LCA) severely reduced basal ROS-GC1 activity. GCAP2 and S100B Ca(2+) signaling modes remained functional, while the GCAP1-modulated mode was diminished. Bicarbonate nearly restored basal activity as well as GCAP2- and S100B-stimulated activities of the F(514)S mutant to normal levels but could not resurrect GCAP1 stimulation. We conclude that GCAP1 and GCAP2 forge distinct pathways through domain-specific modules of ROS-GC1 whereas the S100B and GCAP2 pathways may overlap. The synergistic interlinking of bicarbonate to GCAPs- and S100B-modulated pathways intensifies and tunes the dependence of cyclic GMP synthesis on intracellular Ca(2+). Our study challenges the recently proposed GCAP1 and GCAP2 "overlapping" phototransduction model (Peshenko et al., 2015b). PMID:26858600

  11. 长R-R间期房颤病人的护理

    Institute of Scientific and Technical Information of China (English)

    宋枚子

    2012-01-01

    目的房颤是临床上常见的心律失常之一,也是当代心脏病学的两大流行病学之一。随着动态心电图等心电监护技术的普及,长R-R间期房颤情况愈加多见。发病时常导致患者心慌、心悸、晕厥、黑朦、心力衰竭,脏器供血不足,血栓形成及栓塞等,轻者影响生活质量,重者致死、致残。本文从长R-R间期房颤的病因、临床治疗以及护理等方面进行探讨,以期在以后的工作中防止此类患者发生意外伤害,保证患者的生命安全。%Atrial fibrillation is a common arrhythmia among,Is one of the two major epidemiological Contemporary Cardiology. With dynamic electrocardiogram ECG monitoring technology popularization, long R-R interval of atrial fibrillation more common situation. Often when the incidence of lead in patients with palpitation, heart palpitations, fainting, amaurosis heart failure, organ insufficiency, thrombosis and embolism, It may affect the quality of life, death, disability or. This article from the long R-R interval of atrial fibrillation in the etiology, clinical treatment and nursing were discussed, in order to work in the future to prevent such patients of accident, ensure the life safety of patients.

  12. Progress and challenges in viral vector manufacturing.

    Science.gov (United States)

    van der Loo, Johannes C M; Wright, J Fraser

    2016-04-15

    Promising results in several clinical studies have emphasized the potential of gene therapy to address important medical needs and initiated a surge of investments in drug development and commercialization. This enthusiasm is driven by positive data in clinical trials including gene replacement for Hemophilia B, X-linked Severe Combined Immunodeficiency, Leber's Congenital Amaurosis Type 2 and in cancer immunotherapy trials for hematological malignancies using chimeric antigen receptor T cells. These results build on the recent licensure of the European gene therapy product Glybera for the treatment of lipoprotein lipase deficiency. The progress from clinical development towards product licensure of several programs presents challenges to gene therapy product manufacturing. These include challenges in viral vector-manufacturing capacity, where an estimated 1-2 orders of magnitude increase will likely be needed to support eventual commercial supply requirements for many of the promising disease indications. In addition, the expanding potential commercial product pipeline and the continuously advancing development of recombinant viral vectors for gene therapy require that products are well characterized and consistently manufactured to rigorous tolerances of purity, potency and safety. Finally, there is an increase in regulatory scrutiny that affects manufacturers of investigational drugs for early-phase clinical trials engaged in industry partnerships. Along with the recent increase in biopharmaceutical funding in gene therapy, industry partners are requiring their academic counterparts to meet higher levels of GMP compliance at earlier stages of clinical development. This chapter provides a brief overview of current progress in the field and discusses challenges in vector manufacturing. PMID:26519140

  13. Metastasis of hepatocellular carcinoma presented as a tumor of the maxillary sinus and retrobulbar tumor

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    Kolarević Daniela

    2011-01-01

    Full Text Available Introduction. Hepatocellular carcinoma (HCC is the most frequent primary malignant tumor of the liver. It is usually seen in the 6th and 7th decades of life and chronic hepatitis B is the most frequent cause. Extrahepatic metastasis of HCC is an indicator of a poor prognosis and the most common sites are lungs, bones, lymph nodes, kidneys and adrenal glands. We reported a case of isolated metastasis in the right maxilla, which had been found initially, before the tumor in the liver was diagnosed. Case report. A 70-year-old man underwent dental surgery of the upper right molar. Prolonged bleeding control was difficult for up to two weeks, so the biopsy was performed. Histopathological analysis revealed a metastatic hepatocellular carcinoma. Computerized tomography (CT of the abdomen revealed a diffusely heterogeneous liver parenchyma with irregular borders and two foci of mass lesions. There were metastasis in the spleen and also two pathological retroperitoneal lymph nodes were detected, but no ascit, liver cirrhosis, cholestasis or portal vein thrombosis were seen. CT of the orbital and maxillary regions revealed a tumor mass in the right maxillary sinus, spreading to the alveolar sinus, nasal cavity and partially infratemporal space. A tumor mass was in the right orbit as well, infiltrating the surrounding bones and muscles. Clinically, there was proptosis of the right eye accompanied by amaurosis. The treatment started with chemotherapy based on 5-fluorouracil (sorafenib was not available. After three cycles, control CTs showed a stable disease in the liver, but progression in the right maxillary sinus and orbit. Enucleation of the right eye was performed and postoperative radiotherapy was planed. The patient deteriorated rapidly and died, about 6 months after the disease had been diagnosed. Conclusion. Extrahepatic metastasis of HCC represents a progressive phase of the disease with poor prognosis, so the main aim of the treatment should be

  14. Electroretinographic assessment and diagnostic reappraisal of children with visual dysfunction: A prospective study

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    Vedantham Vasumathy

    2007-01-01

    Full Text Available Purpose: To assess the presence or absence of a retinal cause of visual impairment using electroretinography (ERG in children with no obvious discernable cause on ocular examination. Design: Prospective observational case series. Materials and Methods: A prospective study was carried out involving 120 children with the mean age 4.4±3.2 years with visual dysfunction. All children underwent ERG under general anesthesia using a special handheld mini-Ganzfeld (Kurbisfeld dome. Results: Fifty-two (43.3% children were male and 68 (56.7% were female. The clinical diagnosis was as follows: Leber′s congenital amaurosis (LCA (n=47, achromatopsia (n=25, congenital stationary night blindness (CSNB (n=9 and others (unclassifiable, n=39. The visual acuity ranged from perception of light (PL to PL with projection in children with LCA. In the rest (n=73, some sort of visually guided behavior was discernable. Following ERG, a diagnostic reappraisal resulted as follows: LCA (n=49, achromatopsia (n=28, CSNB (n=4, cone-rod dystrophy (n=22, rod-cone degeneration (n=7, normal (n=8 and others (unclassifiable, n=2. Except for the two unclassifiable cases, ERG was successful in the diagnosis or exclusion of retinal dysfunction in the rest. By Pearson Chi-square test, there was a statistically significant association between the clinical and ERG diagnosis ( P < 0.001. Conclusion: LCA was the commonest cause of visual dysfunction in our series. A statistically significant correlation between clinical and electrophysiological diagnosis was seen. ERG helped in firmly establishing the presence or absence of global retinal dysfunction in the majority (118/120 of pediatric patients with visual dysfunction.

  15. Noninvasive Imaging Reveals Stable Transgene Expression in Mouse Airways After Delivery of a Nonintegrating Recombinant Adeno-Associated Viral Vector.

    Science.gov (United States)

    Vidović, Dragana; Gijsbers, Rik; Jimenez, Ana Quiles; Dooley, James; Van den Haute, Chris; Van der Perren, Anke; Liston, Adrian; Baekelandt, Veerle; Debyser, Zeger; Carlon, Marianne Sylvia

    2016-01-01

    Gene therapy holds promise to cure a wide range of genetic and acquired diseases. Recent successes in recombinant adeno-associated viral vector (rAAV)-based gene therapy in the clinic for hereditary disorders such as Leber's congenital amaurosis and hemophilia B encouraged us to reexplore an rAAV approach for pulmonary gene transfer. Only limited clinical successes have been achieved for airway gene transfer so far, underscoring the need for further preclinical development of rAAV-based gene therapy for pulmonary disorders. We sought to determine the preclinical potential of an airway-tropic serotype, rAAV2/5, encoding reporter genes when delivered to mouse airways. Although several groups have assessed the stability of gene transfer using a nonintegrating rAAV in mouse airways, long-term stability for more than a year has not been reported. Additionally, an extensive quantitative analysis of the specific cell types targeted by rAAV2/5 using cell-specific markers is lacking. We obtained sustained gene expression in upper and lower airways up to 15 months after vector administration, a substantial proportion of the lifespan of a laboratory mouse. In addition, we demonstrated that readministration of rAAV2/5 to the airways is feasible and increases gene expression 14 months after primary vector administration, despite the presence of circulating neutralizing antibodies. Finally, identification of transduced cell types revealed different subpopulations being targeted by rAAV2/5, with 64% of β-galactosidase-positive cells being ciliated cells, 34% club cells in the conducting airways, and 75% alveolar type II cells in the alveoli at 1 month postinjection. This underscores the therapeutic potential of a nonintegrating rAAV vector to develop a gene therapeutic drug for a variety of pulmonary disorders, such as cystic fibrosis, primary ciliary dyskinesia, and surfactant deficiencies. PMID:26567984

  16. THE NUMERICAL REPRESENTATION OF CHILDREN WITH DAMAGED EYESIGHT ON THE TERRITORY OF SKOPJE AND WORK ORGANIZATION WITH THIS POPULATION AT PRESCHOOL PERIOD

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    Snezana TALEVSKA

    1997-09-01

    Full Text Available The binocular function of the eyesight as a process develops as early as the first years of life.Taking into consideration the great number of inherent factors, which disturb the normal development of the eye-sight function, and the great number of causes of damages in the prenatal and natal period, the question of early detection of the reasons, diagnostics and treatment are of utmost importance.That’s possible, only if there is a cooperation among persons that are in the closest contacts with the child:· the mother;· the pediatrician;· the nurse;· the ophthalmologist;· the educator and· the physician.It’s not so necessary to talk about the importance of the sight in the human life, i.e. the importance of the binocular function of the children sight, from the early age when their psycho-physical development is the most flourishing.The importance of the early detection, diagnostics and treatment of the damaged eyesight is great. Especially, this is of great importance for ambliopia, which can be hardly detected at this early period, but it can be easily and successfully treated. We say it is hard to detect because of the delusion and inertness of parents, just during early years from birth to the 3 year, that the child is small and it’s too early to start a treatment.On the contrary, practice has shown that this time is lost and hardly can be compensate, either in means of cure of ambliopia and treatment or rehabilitation of amaurosis.The numerical data of children with damaged eyesight on the territory of Skopje and the need of organized work with this population of children at preschool age will be confirmed and enclosed.

  17. Retinite por citomegalovirus (CMV após terapia imunossupressora para vasculite leucocitoclástica Cytomegalovirus (CMV retinitis after immunossupressive therapy for leukocytoclastic vasculitis

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    Carlos Ewerton Maia Rodrigues

    2009-02-01

    Full Text Available A retinite por citomegalovírus (CMV é uma doença rara que acomete principalmente pacientes com a síndrome da imunodeficiência adquirida (AIDS. No entanto, outros pacientes imunossuprimidos, como os transplantados, os que estão em uso de quimioterápicos, pacientes com lúpus eritematoso sistêmico (LES ou em tratamento com drogas imunossupressoras também podem ser acometidos. O quadro clínico caracteriza-se por visão turva, diminuição da acuidade ou alterações de campo visual, geralmente unilateral, podendo ocorrer deslocamento de retina. A perda visual é progressiva, evolui em ritmo variável até a completa amaurose do olho acometido. O presente relato de caso descreve um paciente com vasculite leucocitoclástica grave submetido à terapia com corticoide em dose imunossupressora que evoluiu com glaucoma, panuveíte por CMV, perda da acuidade visual e infecção bacteriana secundária.Cytomegalovirus (CMV retinitis is a rare disease which mainly affects patients with acquired immunodeficiency syndrome (AIDS. Nevertheless, other immunosuppressed patients, such as the organ transplant recipients, the ones using chemotherapy, patients with systemic lupus erythematosus (SLE or in treatment with immunosuppressive drugs can also be attacked. The clinical characteristics are blurred vision, decrease of the visual acuity or visual field alterations, generally unilateral, with the possibility of retinal detachment. The visual loss is progressive, evolving in a variable rate until complete amaurosis of the attacked eye. The present case report describes a patient with severe leukocytoclastic vasculitis, submitted to corticosteroid therapy in immunosuppressive doses that evolved with glaucoma, panuveitis by CMV, loss of visual acuity and secondary bacterial infection.

  18. Classificação diagnóstica dos portadores de doenças degenerativas de retina, integrantes dos grupos Retina São Paulo e Retina Vale do Paraíba Diagnostic classification of retinal degenerative diseases São Paulo and Vale Retina groups

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    Nichard Unonius

    2003-08-01

    ,5% eram casos isolados. CONCLUSÃO: Destaca-se assim a importância desta classificação como a primeira referência nacional dos padrões de hereditariedade das distrofias retinianas do país. Este é o primeiro passo para se proceder em seguida a classificação genético-molecular baseada no seqüenciamento de cada gene responsável por cada um dos padrões de herança. A freqüência de cada tipo específico é semelhante à encontrada em outros trabalhos epidemiológicos de outros países.PURPOSE: To organize a regional data bank of all individuals that have retinal degenerative diseases, with the aim to classify each patient according to the type of distrophy and pattern of inheritance. METHODS: During the meeting of the São Paulo Retina Group on May 5th, 2001, two hundred and forty-three persons were registered, part of whom provided information concerning ocular, personal and family history and family tree. Ninety-three patients were asked about age, origin, type of dystrophy, family history and family tree information, type of inheritance, other systemic abnormalities and complementary examination. They were classified according to the diagnosis and pattern of inhe-ritance. RESULTS: The distrophies found in the registered two hundred and forty-three patients, were: retinitis pigmentosa, Stargardt disease, Usher syndrome, Leber congenital amaurosis and choroideremia. Of the ninety-three patients examined on the same day, sixty-two had retinitis pigmentosa, thirteen had Stargardt disease, thirteen had Usher syndrome, three had Leber congenital amaurosis and two had choroideremia. The inheritance pattern of the patients with retinitis pigmentosa was autosomal dominant in 4 cases (7%, autosomal recessive in twenty cases (32%, X-linked recessive in 7 cases (11%. Twenty-nine cases were isolated (47% and two had an indeterminate pattern of inheritance (3%. Of the Stargardt disease patients, three (23% were autosomal recessive and ten (77% were isolated cases. Of the

  19. Impact of set-aside management on soil mesofauna

    Science.gov (United States)

    Landi, Silvia; d'Errico, Giada; Mazza, Giuseppe; Mocali, Stefano; Bazzoffi, Paolo; Roversi, Pio Federico

    2014-05-01

    (MI) resulted significantly higher in set-aside managements than in conventional crops in Fagna and Metaponto sites. In contrast, Caorle was characterized by a significant soil degradation (prevalence of extreme colonizers) and any increase of MI values in the set-aside have been not detected. About microarthropods, the taxa richness was significantly higher in set-aside managements than conventional crops in all the sites sampled. QBS index showed the same trend, but the differences were not significant. Caorle site was characterized by a lack of balance in the relative abundance among soil microarthropods taxa. In particular, set-aside managements showed a strong prevalence of an aggressive ants Solenopsis fugax (Hymenoptera: Formicidae). In conclusion, the best results were observed in Fagna and Metaponto sites, where MI and QBS values increased under set-aside management as compared to the conventional. Further analyses will be carried out over a long period to better understand the possible correlation between the enhancement of the organic matter observed in the soils less degraded and the biological quality improvement.

  20. Analyses of species composition and diversity of weed seed bank of main crop fields in Jiangsu Province and its correlation with environmental factors%江苏省主要农田杂草种子库物种组成和多样性及其与环境因子的相关性分析

    Institute of Scientific and Technical Information of China (English)

    章超斌; 马波; 强胜

    2012-01-01

    采用水洗镜检法对江苏省31个农田样点(包括旱田和水田)0~15 cm土层土壤杂草种子库的种类组成和物种多样性进行了调查研究;采用典范对应法分析了杂草种子库种类与环境因子(包括淹水天数、土壤有机质含量、土壤pH、年降水量、年均温、样点经度和样点纬度)的相关性并绘制了样点和种类与环境因子的二维排序散点图.调查结果表明:在31个样点的土壤杂草种子库中共检测到杂草种子15科54种,旱田和水田各有41和45种,二者共有种类占多数但优势种有差异,通泉草[ Mazus japonicus (Thunb.) Kuntze]、异型莎草(Cyperus difformis L.)、水苋菜(Ammannia baccifera L.)、千金子[Leptochloa chinensis (L.) Nees]、棒头革(Polypogon fugax Nees ex Steud.)和牛繁缕[ Malachium aquaticum (L.) Fries]等种类为二者的共有优势种;杂草种类最多的为禾本科(Gramineae)和莎草科(Cyperaceae),分别占种类总数的22.6%和20.8%.旱田不同样点杂草种子库的优势种类变化较大,而水田杂草种子库优势种较稳定;二者优势种频度差异较大,旱田中频度高于0.30的杂草有19种,水田中频度高于0.50的杂草有20种;旱田和水田中平均重要值大于0.03的杂草各有11和9种,这些频度高的种类重要值也较大.旱田和水田土壤种子库种子密度分别为21 015和37 847 m-2,平均为31 008 m-2;旱田3层土壤中种子密度差异不显著,而水田上、中层土壤的种子密度显著高于下层.旱田以夏熟和秋熟杂草为主,而水田则以水田和夏熟杂草为主.按形态类型划分,水田及旱田中杂草种类数和密度从大到小均依次排序为阔叶草类、禾草类、莎草类,且水田中这3类杂草的种类数和种子密度均高于旱田.与旱田相比,水田杂草种子库的物种丰富度指数(S)、Shannon-Wiener 指数(H')和Simpson指数(D)较高,但Pielou均匀度指数(E)较低;旱田杂草种子库的S、H'

  1. RETINOBASE: a web database, data mining and analysis platform for gene expression data on retina

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    Léveillard Thierry

    2008-05-01

    Full Text Available Abstract Background The retina is a multi-layered sensory tissue that lines the back of the eye and acts at the interface of input light and visual perception. Its main function is to capture photons and convert them into electrical impulses that travel along the optic nerve to the brain where they are turned into images. It consists of neurons, nourishing blood vessels and different cell types, of which neural cells predominate. Defects in any of these cells can lead to a variety of retinal diseases, including age-related macular degeneration, retinitis pigmentosa, Leber congenital amaurosis and glaucoma. Recent progress in genomics and microarray technology provides extensive opportunities to examine alterations in retinal gene expression profiles during development and diseases. However, there is no specific database that deals with retinal gene expression profiling. In this context we have built RETINOBASE, a dedicated microarray database for retina. Description RETINOBASE is a microarray relational database, analysis and visualization system that allows simple yet powerful queries to retrieve information about gene expression in retina. It provides access to gene expression meta-data and offers significant insights into gene networks in retina, resulting in better hypothesis framing for biological problems that can subsequently be tested in the laboratory. Public and proprietary data are automatically analyzed with 3 distinct methods, RMA, dChip and MAS5, then clustered using 2 different K-means and 1 mixture models method. Thus, RETINOBASE provides a framework to compare these methods and to optimize the retinal data analysis. RETINOBASE has three different modules, "Gene Information", "Raw Data System Analysis" and "Fold change system Analysis" that are interconnected in a relational schema, allowing efficient retrieval and cross comparison of data. Currently, RETINOBASE contains datasets from 28 different microarray experiments performed

  2. Recombinant adeno-associated virus type 2-mediated gene delivery into the Rpe65-/- knockout mouse eye results in limited rescue

    Science.gov (United States)

    Lai, Chooi-May; Yu, Meaghan JT; Brankov, Meliha; Barnett, Nigel L; Zhou, Xiaohuai; Redmond, T Michael; Narfstrom, Kristina; Rakoczy, P Elizabeth

    2004-01-01

    Background Leber's congenital amaurosis (LCA) is a severe form of retinal dystrophy. Mutations in the RPE65 gene, which is abundantly expressed in retinal pigment epithelial (RPE) cells, account for approximately 10–15% of LCA cases. In this study we used the high turnover, and rapid breeding and maturation time of the Rpe65-/- knockout mice to assess the efficacy of using rAAV-mediated gene therapy to replace the disrupted RPE65 gene. The potential for rAAV-mediated gene treatment of LCA was then analyzed by determining the pattern of RPE65 expression, the physiological and histological effects that it produced, and any improvement in visual function. Methods rAAV.RPE65 was injected into the subretinal space of Rpe65-/- knockout mice and control mice. Histological and immunohistological analyses were performed to evaluate any rescue of photoreceptors and to determine longevity and pattern of transgene expression. Electron microscopy was used to examine ultrastructural changes, and electroretinography was used to measure changes in visual function following rAAV.RPE65 injection. Results rAAV-mediated RPE65 expression was detected for up to 18 months post injection. The delivery of rAAV.RPE65 to Rpe65-/- mouse retinas resulted in a transient improvement in the maximum b-wave amplitude under both scotopic and photopic conditions (76% and 59% increase above uninjected controls, respectively) but no changes were observed in a-wave amplitude. However, this increase in b-wave amplitude was not accompanied by any slow down in photoreceptor degeneration or apoptotic cell death. Delivery of rAAV.RPE65 also resulted in a decrease in retinyl ester lipid droplets and an increase in short wavelength cone opsin-positive cells, suggesting that the recovery of RPE65 expression has long-term benefits for retinal health. Conclusion This work demonstrated the potential benefits of using the Rpe65-/- mice to study the effects and mechanism of rAAV.RPE65-mediated gene delivery into

  3. Bicarbonate and Ca2+ sensing modulators activate photoreceptor ROS-GC1 synergistically

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    Teresa eDuda

    2016-01-01

    Full Text Available Photoreceptor ROS-GC1, a prototype subfamily member of the membrane guanylate cyclase family, is a central component of phototransduction. It is a single transmembrane-spanning protein, composed of modular blocks. In rods, guanylate cyclase activating proteins (GCAPs 1 and 2 bind to its juxtamembrane domain and the C-terminal extension, respectively, to accelerate cyclic GMP synthesis when Ca2+ levels are low. In cones, the additional expression of the Ca2+-dependent guanylate cyclase activating protein (CD-GCAP S100B which binds to its C-terminal extension, supports acceleration of cyclic GMP synthesis at high Ca2+ levels. Independent of Ca2+, ROS-GC1 activity is also stimulated directly by bicarbonate binding to the core catalytic domain. Several enticing molecular features of this transduction system are revealed in the present study. In combination, bicarbonate and Ca2+-dependent modulators raised maximal ROS-GC activity to levels that exceeded the sum of their individual effects. The F514S mutation in ROS-GC1 that causes blindness in type 1 Leber’s congenital amaurosis severely reduced basal ROS-GC1 activity. GCAP2 and S100B Ca2+ signaling modes remained functional, while the GCAP1-modulated mode was diminished. Bicarbonate nearly restored basal activity as well as GCAP2- and S100B-stimulated activities of the F514S mutant to normal levels but could not resurrect GCAP1 stimulation. We conclude that GCAP1 and GCAP2 forge distinct pathways through domain-specific modules of ROS-GC1 whereas the S100B and GCAP2 pathways may overlap. The synergistic interlinking of bicarbonate to GCAPs- and S100B-modulated pathways intensifies and tunes the dependence of cyclic GMP synthesis on intracellular Ca2+. Our study challenges the recently proposed GCAP1 and GCAP2 overlapping phototransduction model (Peshenko, I.V., Olshevskaya, and Dizhoor, A. M. (2015 J Biol. Chem 290, 6913-6924.

  4. Recombinant adeno-associated virus-mediated gene transfer for the potential therapy of adenosine deaminase-deficient severe combined immune deficiency.

    Science.gov (United States)

    Silver, Jared N; Elder, Melissa; Conlon, Thomas; Cruz, Pedro; Wright, Amy J; Srivastava, Arun; Flotte, Terence R

    2011-08-01

    ). Currently, rAAV vectors are being utilized in phase I/II clinical trials for cystic fibrosis, α-1 antitrypsin deficiency, Canavan's disease, Parkinson's disease, hemophilia, limb-girdle muscular dystrophy, arthritis, Batten's disease, and Leber's congenital amaurosis (Flotte et al., 1996 , 2004 ; Kay et al., 2000 ; Aitken et al., 2001 ; Wagner et al., 2002 ; Manno et al., 2003 ; Snyder and Francis, 2005 ; Maguire et al., 2008 ; Cideciyan et al., 2009 ). In this study, we present preclinical data to support the viability of an rAAV-based gene transfer strategy for cure of ADA-SCID. We report efficient transduction of a variety of postmitotic target tissues in vivo, subsequent human ADA (hADA) expression, and enhanced hADA secretion in tissues and blood, with increasing peripheral lymphocyte populations over time. PMID:21142972

  5. Mechanistically distinct mouse models for CRX-associated retinopathy.

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    Nicholas M Tran

    2014-02-01

    Full Text Available Cone-rod homeobox (CRX protein is a "paired-like" homeodomain transcription factor that is essential for regulating rod and cone photoreceptor transcription. Mutations in human CRX are associated with the dominant retinopathies Retinitis Pigmentosa (RP, Cone-Rod Dystrophy (CoRD and Leber Congenital Amaurosis (LCA, with variable severity. Heterozygous Crx Knock-Out (KO mice ("+/-" have normal vision as adults and fail to model the dominant human disease. To investigate how different mutant CRX proteins produce distinct disease pathologies, we generated two Crx Knock-IN (K-IN mouse models: Crx(E168d2 ("E168d2" and Crx(R90W ("R90W". E168d2 mice carry a frameshift mutation in the CRX activation domain, Glu168del2, which is associated with severe dominant CoRD or LCA in humans. R90W mice carry a substitution mutation in the CRX homeodomain, Arg90Trp, which is associated with dominant mild late-onset CoRD and recessive LCA. As seen in human patients, heterozygous E168d2 ("E168d2/+" but not R90W ("R90W/+" mice show severely impaired retinal function, while mice homozygous for either mutation are blind and undergo rapid photoreceptor degeneration. E168d2/+ mice also display abnormal rod/cone morphology, greater impairment of CRX target gene expression than R90W/+ or +/- mice, and undergo progressive photoreceptor degeneration. Surprisingly, E168d2/+ mice express more mutant CRX protein than wild-type CRX. E168d2neo/+, a subline of E168d2 with reduced mutant allele expression, displays a much milder retinal phenotype, demonstrating the impact of Crx expression level on disease severity. Both CRX([E168d2] and CRX([R90W] proteins fail to activate transcription in vitro, but CRX([E168d2] interferes more strongly with the function of wild type (WT CRX, supporting an antimorphic mechanism. E168d2 and R90W are mechanistically distinct mouse models for CRX-associated disease that will allow the elucidation of molecular mechanisms and testing of novel

  6. [Anorexia with sinus bradycardia: a case report].

    Science.gov (United States)

    Wang, Fang-fang; Xu, Ling; Chen, Bao-xia; Cui, Ming; Zhang, Yuan

    2016-02-18

    As anorexia patients always go to the psychiatric clinic, little is concerned about the occurrence of sinus bradycardia in these patients for cardiologists and psychiatrists. The aim of this paper is to discuss the relationship between anorexia and sinus bradycardia, and the feature analysis, differential diagnosis and therapeutic principles of this type of sinus bradycardia. We report a case of sinus bradycardia in an anorexia patient with the clinical manifestations, laboratory exams, auxiliary exams, therapeutic methods, and her prognosis, who was admitted to Peking University Third Hospital recently. The patient was a 19-year-old female, who had the manifestation of anorexia. She lost obvious weight in a short time (about 15 kg in 6 months), and her body mass index was 14.8 kg/m(2). The patient felt apparent palpitation, chest depression and short breath, without dizziness, amaurosis or unconsciousness. Vitals on presentation were notable for hypotension, and bradycardia. The initial exam was significant for emaciation, but without lethargy or lower extremity edema. The electrocardiogram showed sinus bradycardia with her heart rate being 32 beats per minute. The laboratory work -up revealed her normal blood routine, electrolytes and liver function. But in her thyroid function test, the free thyroid (FT) hormones 3 was 0.91 ng/L (2.3-4.2 ng/L),and FT4 was 8.2 ng/L (8.9-18.0 ng/L), which were all lower; yet the thyroid stimulating hormone (TSH) was normal 1.48 IU/mL (0.55-4.78 IU/mL). Ultrasound revealed her normal thyroid. Anorexia is an eating disorder characterized by extremely low body weight, fear of gaining weight or distorted perception of body image, and amenorrhea. Anorexia patients who lose weight apparently in short time enhance the excitability of the parasympathetic nerve, and inhibit the sympathetic nerve which lead to the appearance of sinus bradycardia, and functional abnormalities of multiple systems such as hypothyroidism. But this kind of sinus

  7. Neurossífilis atípica: Relato de caso Atypical neurosyphilis: case report

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    Fábio Leite Gastal

    1995-09-01

    Full Text Available O presente estudo é baseado na observação de um caso de neurossífilis no serviço de internação da Clínica Olivé Leite em agosto-1992. A paciente, do sexo feminino e com 31 anos de idade, foi admitida por apresentar quadro de psicose orgânica no qual predominavam sintomas de tipo deterioração cognitiva (síndrome demencial, associados a elementos paranoides (alucinações e delírios. A investigação diagnóstica evidenciou testes imunológicos positivos para sífilis no sangue e no LCR. Destaca-se este caso pelos seguintes aspectos peculiares: forma da apresentação clínica, gravidade dos sintomas (amaurose e severo déficit cognitivo, sexo, idade e por ser este o primeiro caso diagnosticado no serviço desde 1968 (data do último registro de caso de neurossífilis no seu Banco de Dados. Após penicilinoterapia e seguimento de 9 meses, a paciente apresenta algumas melhoras, caracterizadas por: diminuição da sintomatologia produtiva de tipo alucinatória e delirante, diminuição do déficit cognitivo em termos de orientação e maior produtividade nas atividades sociais e comportamentais.The present study is based on the observation of a case at the inpatient service of Clinica Olivé Leite in August 1992. A 31 years old female patient, showing cognitive deterioration and demential syndrome associated with paranoid elements (hallucination and delirium, was admitted as a case of organic psychosis. Diagnostic investigation evidenced positive tests for syphilis in serum and cerebrospinal fluid. The following peculiar aspects are emphasized in this case: severe clinical presentation, severe presentation symptoms (amaurosis and a severe cognitive deficit, sex, age, and for being the first case diagnosed in the service since 1968 (occasion in wich the last neurosyphilis case was registered in its data bank. In the following nine months, after penicillin therapy, the patient showed some improvement characterized by a reduction of

  8. Mechanical injuries of the eyeball: Frequency, structure, and possibility of the prevention

    Directory of Open Access Journals (Sweden)

    Jovanović Miloš

    2006-01-01

    , etc. According to months in a year and days in a week, the injuries were almost evenly distributed. Considering the period of a day, even 77.4% of the injuries occurred during daytime, from 10 a.m. to 10 p.m. The highest percentage - 43.5% - of the injuries occurred while working something out of working place, while 24.5% of injuries were inflicted at working places. On admission, the majority of patients - 32.9% had visual acuity L+P+, but this visual acuity ranged from amaurosis to 1.0. There were 746 (45.4% contusion injuries and 870 (53.0% penetrating injuries. The rest were the injuries of other ocular adnexa. The majority of primary wound managements were performed in the first 24 hours of the injury - 67.1%. Conclusion. It may be concluded that working population and students are most commonly injured, and that men are five times more frequently injured than women; then, a piece of wood, sharp objects and glass are the most often causes of injury; the number of contusion and penetrating injuries is equal, and that required primary surgical wound management is most often performed in the first 24 hours from the injury. Further analysis of these factors suggests that many of these injuries could have been prevented, and consequently long-term treatment and treatment costs could have been evaded. Most important is that permanent disability due to visual impairment or even blindness of the injured eye could have been avoided.

  9. Delivering Transgenic DNA Exceeding the Carrying Capacity of AAV Vectors.

    Science.gov (United States)

    Hirsch, Matthew L; Wolf, Sonya J; Samulski, R J

    2016-01-01

    Gene delivery using recombinant adeno-associated virus (rAAV) has emerged to the forefront demonstrating safe and effective phenotypic correction of diverse diseases including hemophilia B and Leber's congenital amaurosis. In addition to rAAV's high efficiency of transduction and the capacity for long-term transgene expression, the safety profile of rAAV remains unsoiled in humans with no deleterious vector-related consequences observed thus far. Despite these favorable attributes, rAAV vectors have a major disadvantage preventing widespread therapeutic applications; as the AAV capsid is the smallest described to date, it cannot package "large" genomes. Currently, the packaging capacity of rAAV has yet to be definitively defined but is approximately 5 kb, which has served as a limitation for large gene transfer. There are two main approaches that have been developed to overcome this limitation, split AAV vectors, and fragment AAV (fAAV) genome reassembly (Hirsch et al., Mol Ther 18(1):6-8, 2010). Split rAAV vector applications were developed based upon the finding that rAAV genomes naturally concatemerize in the cell post-transduction and are substrates for enhanced homologous recombination (HR) (Hirsch et al., Mol Ther 18(1):6-8, 2010; Duan et al., J Virol 73(1):161-169, 1999; Duan et al., J Virol 72(11):8568-8577, 1998; Duan et al., Mol Ther 4(4):383-391, 2001; Halbert et al., Nat Biotechnol 20(7):697-701, 2002). This method involves "splitting" the large transgene into two separate vectors and upon co-transduction, intracellular large gene reconstruction via vector genome concatemerization occurs via HR or nonhomologous end joining (NHEJ). Within the split rAAV approaches there currently exist three strategies: overlapping, trans-splicing, and hybrid trans-splicing (Duan et al., Mol Ther 4(4):383-391, 2001; Halbert et al., Nat Biotechnol 20(7):697-701, 2002; Ghosh et al., Mol Ther 16(1):124-130, 2008; Ghosh et al., Mol Ther 15(4):750-755, 2007). The other major

  10. Current situation and the future of retinal gene therapy%视网膜疾病基因治疗的现状与未来

    Institute of Scientific and Technical Information of China (English)

    庞继景

    2014-01-01

    Following the development of technologies in molecular biology,more and more mutant genes that cause retinal degenerative diseases have been found.Meanwhile,many naturally occurring or genetically engineered animal models have showed similar gene mutations and phenotypes as the human inherited retinal diseases,which have led to the development of a variety of therapeutic strategies for those traditionally incurable inherited diseases.Following Leber congenital amaurosis 2 (LCA2) gene therapy clinical trial,more gene therapy clinical trials including retinitis pigmentosa (RP) with MERTK mutation,Stargardt disease with ABCA4 mutation,Usher syndrome with MYO7A mutation and age-related macular degeneration (AMD) are ongoing.Adeno associated virtal (AAV) vectormediated gene replacement therapy that covers the whole retina showed great potential to cure early stage of those patients;while,gene replacement therapy combined with other approaches like treatment with anti-apoptotic agent and/or neurotropic factor,which can extend the therapeutic window in middle to late stages of those patients,is a potentially promising strategy for improving photoreceptor function and significantly slowing the process of retinal degeneration.%近年来人类基因组学研究的不断深入,基因突变检测的方法日新月异,尤其是基因芯片和全外显子扫描技术的出现,使突变基因检测变得更加简单和高效,越来越多的导致视网膜疾病的突变基因被确认.一些自然动物模型和基因敲除动物模型广泛应用于实验研究,促进了视网膜变性类疾病治疗研究的进展.此外,由于基因转染载体技术的进步,视网膜变性疾病的基因治疗研究也取得了长足的进步.随着2008年开始的Leber先天性黑矇(LCA2)临床试验的顺利开展,为更多的隐性遗传性视网膜变性类疾病的基因治疗奠定了良好的基础,如应用基因替代疗法治疗MERTK基因突变引起的视网膜色素变

  11. 厌食症合并窦性心动过缓1例%Anorexia with sinus bradycardia:a case report

    Institute of Scientific and Technical Information of China (English)

    王方芳; 徐玲; 陈宝霞; 崔鸣; 张媛

    2016-01-01

    SUMMARY Asanorexiapatientsalwaysgotothepsychiatricclinic,littleisconcernedabouttheoccur-rence of sinus bradycardia in these patients for cardiologists and psychiatrists.The aim of this paper is to discuss the relationship between anorexia and sinus bradycardia,and the feature analysis,differential diagnosis and therapeutic principles of this type of sinus bradycardia.We report a case of sinus bradycar-dia in an anorexia patient with the clinical manifestations,laboratory exams,auxiliary exams,therapeutic methods,and her prognosis,who was admitted to Peking University Third Hospital recently.The patient was a 1 9-year-old female,who had the manifestation of anorexia.She lost obvious weight in a short time (about 1 5 kg in 6 months),and her body mass index was 1 4.8 kg/m2 .The patient felt apparent palpi-tation,chest depression and short breath,without dizziness,amaurosis or unconsciousness.Vitals on presentation were notable for hypotension,and bradycardia.The initial exam was significant for emacia-tion,but without lethargy or lower extremity edema.The electrocardiogram showed sinus bradycardia with her heart rate being 32 beats per minute.The laboratory work-up revealed her normal blood routine,elec-trolytes and liver function.But in her thyroid function test,the free thyroid (FT)hormones 3 was 0.91 ng/L (2.3-4.2 ng/L),and FT4 was 8.2 ng/L(8.9 -1 8.0 ng/L),which were all lower;yet the thy-roid stimulating hormone(TSH)was normal 1 .48 IU/mL(0.55 -4.78 IU/mL).Ultrasound revealed her normal thyroid.Anorexia is an eating disorder characterized by extremely low body weight,fear of gaining weight or distorted perception of body image,and amenorrhea.Anorexia patients who lose weight appa-rently in short time enhance the excitability of the parasympathetic nerve,and inhibit the sympathetic nerve which lead to the appearance of sinus bradycardia,and functional abnormalities of multiple systems such as hypothyroidism.But this kind of sinus bradycardia and hypothyroidism

  12. Prevalence and prognostic value of early repolarization pattern in Chinese adolescent%中国部分区域青少年早复极的检出率及随访

    Institute of Scientific and Technical Information of China (English)

    刘文玲; 杨杰; 马占锋; 尹广利; 周玉安; 周广华; 李蕾; 张红; 张岚; 赵杰强; 朱天刚; 赵博

    2012-01-01

    Objective To understand the prevalence and prognosis of early repolarization ( ER) in Chinese adolescent. Method Students from some high schools and universities in Beijing were screened by ECG in 2008 -2010. Medical history, family history, and physical examination, including echocardiography, Holter monitoring were recorded if necessary. Students with ER had follow-up. Diagnostic criteria for ER: J-point elevation at least 0. 1 mV and QRS notching or slurring more than 2 consecutive leads in 12-lead electrocardiography, ST segment elevation concave upward, high peak T-wave. ECG diagnosis were made by two experienced cardiologists. Results 13 405 valid ECG and related information were obtained, age 15-22 years old, male to female ratio 1. 01: 1, including 34 provinces and autonomous regions and special administrative regions from China, Covering Han, Manzu, Mongolian, Miao, Tibetan, Korean, and Dong, mainly Han. Total of 135 cases of ER were found, male 111 , female 24. The prevalence was 1%. They were mostly in inferior (79 cases) , next was both in inferior and lateral(29 cases) . The forms were mainly notching or slurring. Follow-up of 12-36 months, no one had sudden cardiac death and other cardiovascular events, only 1 case had amaurosis, but no arrhythmias were recorded. Conclusion The prevalence of ER in Chinese adolescent is 1% based on this population, mainly in inferior and lateral leads; ER is generally benign. [ Chinese Journal of Cardiac Pacing and Electrophysiology ,2012,26 (6):498-500]%目的 了解中国青少年早复极(ER)的发生率及预后.方法 2008年9月至2010年10月,对北京市部分中学高一年级和职业中学新生、大学新人学的本科生进行筛查,包括询问病史及家族史,体格检查,心电图检查,必要时做超声心动图、动态心电图.并进行随访.ER诊断标准:心电图连续2个导联以上J点抬高至少0.1 mV,呈顿挫或切迹样,ST段呈凹面向上抬高,T波高尖.心电图由2名心

  13. Distrofias retinianas da infância: análise retrospectiva Retinal dystrophies in childhood: retrospective analysis

    Directory of Open Access Journals (Sweden)

    Heloisa Andrade Maestrini

    2004-12-01

    distrofias retinianas da infância são um grupo heterogêneo de doenças que se manifestam por meio de sintomas inespecíficos. Uma análise cuidadosa dos sintomas, o exame oftalmológico completo e os exames complementares, principalmente ERG, testes de visão de cores e campo visual, podem ser úteis em seu diagnóstico.PURPOSE: To describe the clinical features and the results of diagnostic methods in all patients with diagnosis of one of the following retinal dystrophies: Leber congenital amaurosis (LCA, achromatopsia, cone distrophy or cone-rod distrophy, examined at the Low Vision Department of the Federal University of Minas Gerais, in the period of 1992 to 2003. METHODS: Retrospective analysis of charts of 40 patients. Ten had LCA, 17 had achromatopsia, 6 had cone distrophy and 7 had cone-rod distrophy. RESULTS: Visual acuity was extremely low in patients with LCA, ranging from 20/710 to light perception. The mean value for achromatopsia was 20/200, 20/280 for cone distrophy and 20/260 for cone-rod distrophy. High hyperopia was the most common refractional error in LCA patients. Hyperopia was more frequent in cases of achromatopsia and cone distrophy, while in cone-rod distrophy myopia predominated. Fundoscopy was altered in most cases of LCA, cone distrophy and rod-cone distrophy, and normal in most cases of achromatopsia. Oculodigital sign and enophtalmus were found only in LCA patients while photofobia and color vision defects prevailed in other groups. Nistagmus and strabismus were frequent findings in all groups. There was a high incidence of delayed neuro-psycho-motor development in LCA patients. Two of them had also associated genetic syndromes. Patients presented symptoms very early in life in LCA and achromatopsia, while in cone and cone-rod distrophies symptoms appeared later, but never after the age of 10. Consanguinity and positive familial history were strongly associated in all groups. The ERG was extinct in LCA, showed reduced photopic response in