Research Topics
Genomes and Genes
| Samuel JacobsonSummaryAffiliation: University of Pennsylvania Country: USA Publications
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Detail Information
Publications
Safety of recombinant adeno-associated virus type 2-RPE65 vector delivered by ocular subretinal injectionSamuel G Jacobson
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA
Mol Ther 13:1074-84. 2006..5-log unit range of vector doses proved efficacious. The efficacy and toxicity limits defined in this study lead to suggestions for the design of a subretinal AAV-2/2.RPE65 human trial of RPE65-associated LCA...
Determining consequences of retinal membrane guanylyl cyclase (RetGC1) deficiency in human Leber congenital amaurosis en route to therapy: residual cone-photoreceptor vision correlates with biochemical properties of the mutantsSamuel G Jacobson
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
Hum Mol Genet 22:168-83. 2013..We postulate a relationship between the level of RetGC1 activity and the degree of cone vision abnormality, and argue for cone function being the efficacy outcome in clinical trials of gene augmentation therapy in LCA1...- Disease expression of RP1 mutations causing autosomal dominant retinitis pigmentosaS G Jacobson
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, USA
Invest Ophthalmol Vis Sci 41:1898-908. 2000..To determine the disease expression in heterozygotes for mutations in the RP1 gene, a newly identified cause of autosomal dominant retinitis pigmentosa (adRP)... 
Usher syndromes due to MYO7A, PCDH15, USH2A or GPR98 mutations share retinal disease mechanismSamuel G Jacobson
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Hum Mol Genet 17:2405-15. 2008..The results point to the photoreceptor cell as the therapeutic target for USH treatment trials, such as MYO7A somatic gene replacement therapy...- Identifying photoreceptors in blind eyes caused by RPE65 mutations: Prerequisite for human gene therapy successSamuel G Jacobson
Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 102:6177-82. 2005.... - Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal laminationSamuel G Jacobson
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Hum Mol Genet 12:1073-8. 2003..The results suggest that the CRB1 disease pathway disturbs the development of normal human retinal organization by interrupting naturally occurring apoptosis... - Human cone photoreceptor dependence on RPE65 isomeraseSamuel G Jacobson
Scheie Eye Institute, Department of Ophthalmology, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 104:15123-8. 2007.... - Leber congenital amaurosis caused by an RPGRIP1 mutation shows treatment potentialSamuel G Jacobson
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Ophthalmology 114:895-8. 2007..To determine the treatment potential in Leber congenital amaurosis (LCA) resulting from an RPGRIP1 (retinitis pigmentosa GTPase regulating-interacting protein 1) mutation, a form of LCA with recent gene therapy success in an animal model... - Nuclear receptor NR2E3 gene mutations distort human retinal laminar architecture and cause an unusual degenerationSamuel G Jacobson
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia 19104, USA
Hum Mol Genet 13:1893-902. 2004..The later-stage dysplastic appearance suggests a previously unrecognized proliferative response in human retinal degeneration... - RDH12 and RPE65, visual cycle genes causing leber congenital amaurosis, differ in disease expressionSamuel G Jacobson
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Invest Ophthalmol Vis Sci 48:332-8. 2007..The relationship of retinal organization and visual function in patients with RDH12 mutations was determined and comparisons made with the disease from mutations in another visual cycle gene, RPE65... - Safety in nonhuman primates of ocular AAV2-RPE65, a candidate treatment for blindness in Leber congenital amaurosisSamuel G Jacobson
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Hum Gene Ther 17:845-58. 2006..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... - Remodeling of the human retina in choroideremia: rab escort protein 1 (REP-1) mutationsSamuel G Jacobson
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Invest Ophthalmol Vis Sci 47:4113-20. 2006..The recent report of a mouse model for CHM prompts the need for reassessment of the human disease in anticipation of treatment initiatives... - Photoreceptor layer topography in children with leber congenital amaurosis caused by RPE65 mutationsSamuel G Jacobson
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Invest Ophthalmol Vis Sci 49:4573-7. 2008..To study the topography of photoreceptor loss early in the course of Leber congenital amaurosis (LCA) caused by RPE65 mutations... - Human retinal disease from AIPL1 gene mutations: foveal cone loss with minimal macular photoreceptors and rod function remainingSamuel G Jacobson
Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA, USA
Invest Ophthalmol Vis Sci 52:70-9. 2011..To determine the human retinal phenotype caused by mutations in the gene encoding AIPL1 (Aryl hydrocarbon receptor-interacting protein-like 1) now that there are proof-of-concept results for gene therapy success in Aipl1-deficient mice... - Novel mutation in the TIMP3 gene causes Sorsby fundus dystrophySamuel G Jacobson
Scheie Eye Institute, 51 N 39th St, Philadelphia, PA 19104, USA
Arch Ophthalmol 120:376-9. 2002..To determine the molecular basis of a retinopathy previously described as dominant macular subretinal neovascularization with peripheral retinal degeneration... - Normal central retinal function and structure preserved in retinitis pigmentosaSamuel G Jacobson
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Invest Ophthalmol Vis Sci 51:1079-85. 2010..To determine whether normal function and structure, as recently found in forms of Usher syndrome, also occur in a population of patients with nonsyndromic retinitis pigmentosa (RP)... - Retinal disease course in Usher syndrome 1B due to MYO7A mutationsSamuel G Jacobson
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA
Invest Ophthalmol Vis Sci 52:7924-36. 2011.... - Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 yearsSamuel G Jacobson
Scheie Eye Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA
Arch Ophthalmol 130:9-24. 2012..To determine the safety and efficacy of subretinal gene therapy in the RPE65 form of Leber congenital amaurosis using recombinant adeno-associated virus 2 (rAAV2) carrying the RPE65 gene... - Defining the residual vision in leber congenital amaurosis caused by RPE65 mutationsSamuel G Jacobson
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Invest Ophthalmol Vis Sci 50:2368-75. 2009..To quantify the residual vision in Leber congenital amaurosis (LCA) caused by RPE65 mutations... - Phenotypic marker for early disease detection in dominant late-onset retinal degenerationS G Jacobson
Department of Ophthalmology, Scheie Eye Institute, 51 N 39th Street, University of Pennsylvania, Philadelphia, PA 19104, USA
Invest Ophthalmol Vis Sci 42:1882-90. 2001..To define early disease expression in autosomal dominant late-onset retinal degeneration (L-ORD), a retinopathy that becomes symptomatic after age 50 and is characterized histopathologically by sub-RPE deposits... - Leber congenital amaurosis caused by Lebercilin (LCA5) mutation: retained photoreceptors adjacent to retinal disorganizationSamuel G Jacobson
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Mol Vis 15:1098-106. 2009..To determine the retinal disease expression in the rare form of Leber congenital amaurosis (LCA) caused by Lebercilin (LCA5) mutation... - Disease boundaries in the retina of patients with Usher syndrome caused by MYO7A gene mutationsSamuel G Jacobson
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Invest Ophthalmol Vis Sci 50:1886-94. 2009..To study retinal microstructure in Usher Syndrome type 1B (USH1B) caused by MYO7A mutations as a prelude to treatment initiatives... - Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotypeSharon B Schwartz
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Invest Ophthalmol Vis Sci 46:734-43. 2005..To investigate the retinal disease expression in USH2C, the subtype of Usher syndrome type 2 recently shown to be caused by mutation in the VLGR1 gene, and compare results with those from USH2A, a more common cause of Usher syndrome... - Visual acuity in patients with Leber's congenital amaurosis and early childhood-onset retinitis pigmentosaSaloni Walia
Department of Ophthalmology, University of Illinois at Chicago, Chicago, Illinois, USA
Ophthalmology 117:1190-8. 2010..To correlate visual acuity of patients with Leber's congenital amaurosis (LCA) and early childhood-onset retinitis pigmentosa (RP) with mutations in underlying LCA genes... - In utero gene therapy rescues vision in a murine model of congenital blindnessNadine S Dejneka
F.M. Kirby Center and Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, 51 N. 39th Street, Philadelphia, PA 19104-2689, USA
Mol Ther 9:182-8. 2004..The results demonstrate AAV-mediated correction of the deficit and suggest that in utero retinal gene delivery may be a useful approach for treating a variety of blinding congenital retinal diseases... - Clinicopathologic effects of mutant GUCY2D in Leber congenital amaurosisAnn H Milam
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, 51 North 39th Street, Philadelphia, PA 19104, USA
Ophthalmology 110:549-58. 2003..To study the retinal degeneration in an 11 -year-old patient with Leber congenital amaurosis (LCA) caused by mutation in GUCY2D... - Impairment of the transient pupillary light reflex in Rpe65(-/-) mice and humans with leber congenital amaurosisTomas S Aleman
Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Invest Ophthalmol Vis Sci 45:1259-71. 2004..To determine the impairment of the transient pupillary light reflex (TPLR) due to severe retinal dysfunction and degeneration in a murine model of Leber congenital amaurosis (LCA) and in patients with the disease... - Retinal disease expression in Bardet-Biedl syndrome-1 (BBS1) is a spectrum from maculopathy to retina-wide degenerationAmir A Azari
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA
Invest Ophthalmol Vis Sci 47:5004-10. 2006..To define the retinal phenotype in patients with the Bardet-Biedl syndrome and mutations in the BBS1 gene... - Electroretinographic analyses of Rpe65-mutant rd12 mice: developing an in vivo bioassay for human gene therapy trials of Leber congenital amaurosisAlejandro J Roman
Department of Ophthalmology, Scheie Eye Institute, Philadelphia, PA, USA
Mol Vis 13:1701-10. 2007..Progress in early-phase clinical trials of RPE65-LCA prompted us to begin development of an in vivo bioassay of clinical grade vector stability for later-phase trials... - Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trialWilliam W Hauswirth
Department of Ophthalmology, University of Florida, Gainesville, FL 32610, USA
Hum Gene Ther 19:979-90. 2008..99). Comparisons are drawn between the present work and two other studies of ocular gene therapy for RPE65-LCA that were carried out contemporaneously and reported... - De novo mutation in the RP1 gene (Arg677ter) associated with retinitis pigmentosaSharon B Schwartz
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Invest Ophthalmol Vis Sci 44:3593-7. 2003..The Arg677ter mutation in the RP1 gene is one of the most common causes of autosomal dominant retinitis pigmentosa (RP). In the current study, a de novo Arg677ter RP1 gene mutation was identified in a patient with RP... - Harmonin in the murine retina and the retinal phenotypes of Ush1c-mutant mice and human USH1CDavid S Williams
Jules Stein Eye Institute, Department of Ophthalmology, UCLA School of Medicine, Los Angeles, CA 90095 7008, USA
Invest Ophthalmol Vis Sci 50:3881-9. 2009..To investigate the expression of harmonin in the mouse retina, test for ultrastructural and physiological mutant phenotypes in the retina of an Ush1c mutant mouse, and define in detail the retinal phenotype in human USH1C... - Spinocerebellar ataxia type 7 (SCA7) shows a cone-rod dystrophy phenotypeTomas S Aleman
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Exp Eye Res 74:737-45. 2002.... - Retinal disease in Usher syndrome III caused by mutations in the clarin-1 geneWaldo Herrera
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Invest Ophthalmol Vis Sci 49:2651-60. 2008..To determine the retinal phenotype of Usher syndrome type III (USH3A) caused by clarin-1 (CLRN1) gene mutations in a non-Finnish population... - Quantifying rod photoreceptor-mediated vision in retinal degenerations: dark-adapted thresholds as outcome measuresAlejandro J Roman
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Exp Eye Res 80:259-72. 2005.... - Retinal disease in Rpe65-deficient mice: comparison to human leber congenital amaurosis due to RPE65 mutationsRafael C Caruso
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Invest Ophthalmol Vis Sci 51:5304-13. 2010..To quantify the retinal disease in Rpe65-deficient mice across a wide age span and compare the results to those in humans with Leber congenital amaurosis (LCA) caused by RPE65 mutations... - Macular pigment and lutein supplementation in choroideremiaJacque L Duncan
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Exp Eye Res 74:371-81. 2002..There was no short-term change in the central vision of the patients on the supplement, but long-term influences of lutein supplementation on disease natural history warrant further study... - In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosaArtur V Cideciyan
Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 102:5233-8. 2005..These experiments provide a platform to study mechanisms of neuronal injury, repair, compensation, and degeneration. The data also argue for a gene-specific clinical trial of light reduction in human rhodopsin disease... - Loss of cone photoreceptors caused by chromophore depletion is partially prevented by the artificial chromophore pro-drug, 9-cis-retinyl acetateTadao Maeda
Department of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106 4965, USA
Hum Mol Genet 18:2277-87. 2009..These results suggest that chronic lack of chromophore leads to progressive loss of cones in mice and humans. Therapy for LCA patients should be geared toward early adequate delivery of chromophore to cone photoreceptors... - ABCA4 disease progression and a proposed strategy for gene therapyArtur V Cideciyan
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA
Hum Mol Genet 18:931-41. 2009..Genotype-based inclusion/exclusion criteria and prediction of the age of retina-wide disease initiation will be invaluable for selecting appropriate candidates for clinical trials in ABCA4 disease... - Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kineticsArtur V Cideciyan
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 105:15112-7. 2008..Cone-sensitivity recovery time was rapid. These results demonstrate dramatic, albeit imperfect, recovery of rod- and cone-photoreceptor-based vision after RPE65 gene therapy... - Macular pigment and lutein supplementation in ABCA4-associated retinal degenerationsTomas S Aleman
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Invest Ophthalmol Vis Sci 48:1319-29. 2007..To determine macular pigment (MP) optical density (OD) in patients with ABCA4-associated retinal degenerations (ABCA4-RD) and the response of MP and vision to supplementation with lutein... 
Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutationGeoffrey K Aguirre
Department of Neurology, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
PLoS Med 4:e230. 2007..We therefore studied the cortex of RPE65-mutant dogs before and after retinal gene therapy. Then, we inquired whether there is visual pathway integrity and responsivity in adult humans with LCA due to RPE65 mutations (RPE65-LCA)...- Cone deactivation kinetics and GRK1/GRK7 expression in enhanced S cone syndrome caused by mutations in NR2E3Artur V Cideciyan
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Invest Ophthalmol Vis Sci 44:1268-74. 2003..To determine the relationship between cone deactivation kinetics in patients with the enhanced S cone syndrome (ESCS) caused by mutations in NR2E3 and the immunoreactivity to G-protein-coupled receptor kinase 1 (GRK1) and GRK7... - Full-field stimulus testing (FST) to quantify visual perception in severely blind candidates for treatment trialsAlejandro J Roman
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Physiol Meas 28:N51-6. 2007..With this advance, inclusion and exclusion criteria can be developed and safety as well as efficacy outcomes measured in upcoming treatment trials of severe retinal blindness... - Reduced-illuminance autofluorescence imaging in ABCA4-associated retinal degenerationsArtur V Cideciyan
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia 19104, and Howard Hughes Medical Institute, University of Iowa Hospitals and Clinics, Iowa City 52242, USA
J Opt Soc Am A Opt Image Sci Vis 24:1457-67. 2007.... - CERKL mutations cause an autosomal recessive cone-rod dystrophy with inner retinopathyTomas S Aleman
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Invest Ophthalmol Vis Sci 50:5944-54. 2009..To define the phenotype of the retinal degeneration associated with mutations in the CERKL gene... - Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 yearArtur V Cideciyan
Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
Hum Gene Ther 20:999-1004. 2009..The safety and efficacy of human retinal gene transfer with rAAV2-RPE65 vector extends to at least 1 year posttreatment... - Mutations in ABCA4 result in accumulation of lipofuscin before slowing of the retinoid cycle: a reappraisal of the human disease sequenceArtur V Cideciyan
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA
Hum Mol Genet 13:525-34. 2004..Knowledge of the human ABCA4 disease sequence will be critical for defining rates of progression, selecting appropriate patients and retinal locations for future therapy, and choosing appropriate treatment outcomes... - Retinal laminar architecture in human retinitis pigmentosa caused by Rhodopsin gene mutationsTomas S Aleman
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Invest Ophthalmol Vis Sci 49:1580-90. 2008..To determine the underlying retinal micropathology in subclasses of autosomal dominant retinitis pigmentosa (ADRP) caused by rhodopsin (RHO) mutations... - ABCA4-associated retinal degenerations spare structure and function of the human parapapillary retinaArtur V Cideciyan
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Invest Ophthalmol Vis Sci 46:4739-46. 2005..To study the parapapillary retinal region in patients with ABCA4-associated retinal degenerations... - The nuclear receptor NR2E3 plays a role in human retinal photoreceptor differentiation and degenerationAnn H Milam
Scheie Eye Institute and F M Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA
Proc Natl Acad Sci U S A 99:473-8. 2002..Degeneration of the NR2E3 retina may result from defective development, known S cone fragility, or abnormal maintenance of mature photoreceptors... - Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosisArtur V Cideciyan
Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Hum Mutat 28:1074-83. 2007.... - Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degenerationJames S Friedman
Department of Ophthalmology, W K Kellogg Eye Center, University of Michigan, Ann Arbor, MI 48105, USA
Am J Hum Genet 79:1059-70. 2006..We suggest that the retinopathy-associated RD3 protein is part of subnuclear protein complexes involved in diverse processes, such as transcription and splicing... - Inner retinal abnormalities in X-linked retinitis pigmentosa with RPGR mutationsTomas S Aleman
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Invest Ophthalmol Vis Sci 48:4759-65. 2007..To investigate in vivo the retinal microstructure in X-linked retinitis pigmentosa (XLRP) caused by RPGR mutations as a prelude to treatment initiatives for this common form of RP... - In vivo micropathology of Best macular dystrophy with optical coherence tomographyMichael J Pianta
Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 51 N, 39th Street, Philadelphia, PA 19104, USA
Exp Eye Res 76:203-11. 2003.... - Subconjunctivally implantable hydrogels with degradable and thermoresponsive properties for sustained release of insulin to the retinaGauri P Misra
Department of Pharmaceutical Sciences, School of Pharmacy, Thomas Jefferson University, 130 South 9th Street, Philadelphia, PA 19107, USA
Biomaterials 30:6541-7. 2009..These subconjunctivally implantable hydrogels have potential for long-term periocular delivery of insulin or other drugs to treat diabetic retinopathy and other retinal diseases... - Nonhuman primate models for diabetic ocular neovascularization using AAV2-mediated overexpression of vascular endothelial growth factorCorinna Lebherz
Department of Medical Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 190104-6069, USA
Diabetes 54:1141-9. 2005..Nonhuman primate models will be useful in testing long-term safety and efficacy of novel therapeutic agents for blinding neovascular diseases... - Early age-related maculopathy and self-reported visual difficulty in daily lifeKay Scilley
Department of Ophthalmology, School of Medicine, University of Alabama at Birmingham, 700 S 18th Street, Birmingham, AL 35294-0009, USA
Ophthalmology 109:1235-42. 2002..Scotopic dysfunction, a functional marker of early ARM, is linked to reported night driving problems. Even when acuity impairment occurs in one eye only, patients report difficulties with day driving and near and far vision tasks... - Mutation analysis of NR2E3 and NRL genes in Enhanced S Cone SyndromeAlan F Wright
MRC Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom
Hum Mutat 24:439. 2004.... - CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsiaSusanne Kohl
Molekulargenetisches Labor, Universitäts Augenklinik Tübingen, Abt Pathophysiologie des Sehens und Neuroophthalmologie, Germany
Eur J Hum Genet 13:302-8. 2005..This indicates that the CNGB3/ACHM3 locus on chromosome 8q21 is the major locus for achromatopsia in patients of European origin or descent... - Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient populationXiao Mei Ouyang
Department of Otolaryngology D 48, University of Miami, 1666 NW 12th Avenue, Miami, FL 33136, USA
Hum Genet 116:292-9. 2005..The present study suggests that mutations in MYO7A and CDH23 are the two major components of causes for USH1, while PCDH15, USH1C, and SANS are less frequent causes... - In vivo function of the orphan nuclear receptor NR2E3 in establishing photoreceptor identity during mammalian retinal developmentHong Cheng
Neuroscience Graduate Program, Department of Ophthalmology and Visual Sciences, W K Kellogg Eye Center, University of Michigan, Ann Arbor 48105, USA
Hum Mol Genet 15:2588-602. 2006..Our studies reveal a critical role of NR2E3 in establishing functional specificity of NRL-expressing photoreceptor precursors during retinal neurogenesis... - Retinal degeneration associated with RDH12 mutations results from decreased 11-cis retinal synthesis due to disruption of the visual cycleDebra A Thompson
Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor 48105, USA, and Unidad de Genética Médica y Diagnóstico Prenatal, Hospitales Universitarios Virgen del Rocio, Seville, Spain
Hum Mol Genet 14:3865-75. 2005..Haplotype analysis in the family in which LCA3 was mapped excluded RDH12 as the LCA3 gene and thus suggests the presence of a novel arRD gene in this region... - Mutation in a short-chain collagen gene, CTRP5, results in extracellular deposit formation in late-onset retinal degeneration: a genetic model for age-related macular degenerationCaroline Hayward
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK
Hum Mol Genet 12:2657-67. 2003..These results indicate a novel disease mechanism involving abnormal adhesion between RPE and Bruch's membrane... - Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindnessGregory M Acland
Baker Institute, Cornell University, Hungerford Hill Road, Ithaca, NY 14853, USA
Mol Ther 12:1072-82. 2005..Successful, stable restoration of rod and cone photoreceptor function in these dogs has important implications for treatment of human patients affected with Leber congenital amaurosis caused by RPE65 mutations... - Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosaJames W Kijas
James A Baker Institute for Animal Health, Cornell University, 47 Hungerford Hill Road, Ithaca, NY 14853, USA
Proc Natl Acad Sci U S A 99:6328-33. 2002..The RHO mutant dog also becomes the large animal needed for preclinical trials of therapies for a major subset of human retinopathies... - Retinal dystrophy due to paternal isodisomy for chromosome 1 or chromosome 2, with homoallelism for mutations in RPE65 or MERTK, respectivelyDebra A Thompson
Department of Ophthalmology and Visual Sciences, University of Michigan Medical School, Ann Arbor, MI, USA
Am J Hum Genet 70:224-9. 2002.... - A comprehensive mutation analysis of RP2 and RPGR in a North American cohort of families with X-linked retinitis pigmentosaDebra K Breuer
Department of Human Genetics, W K Kellogg Eye Center, University of Michigan, 1000 Wall Street, Ann Arbor, MI 48105, USA
Am J Hum Genet 70:1545-54. 2002..We also discuss the implications of our studies for genetic diagnosis, genotype-phenotype correlations, and gene-based therapy... - Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndromeKirk Mykytyn
Department of Pediatrics, Division of Medical Genetics and the Howard Hughes Medical Institute, University of Iowa, Iowa City, Iowa 52242, USA
Nat Genet 31:435-8. 2002..Here we report the identification of the gene BBS1 and show that a missense mutation of this gene is a frequent cause of BBS. In addition, we provide data showing that this common mutation is not involved in triallelic inheritance... - ABCA4 gene analysis in patients with autosomal recessive cone and cone rod dystrophiesVeronique B D Kitiratschky
Institute for Ophthalmic Research, Centre for Ophthalmology, University Tübingen, Tubingen, Germany
Eur J Hum Genet 16:812-9. 2008.... - Lentiviral expression of retinal guanylate cyclase-1 (RetGC1) restores vision in an avian model of childhood blindnessMelissa L Williams
Department of Neuroscience, University of Florida McKnight Brain Institute, Gainesville, Florida, USA
PLoS Med 3:e201. 2006..These results represent a first step toward development of gene therapies for one of the more common forms of childhood blindness... - Mutation screening of patients with Leber Congenital Amaurosis or the enhanced S-Cone Syndrome reveals a lack of sequence variations in the NRL geneCeren Acar
Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, MI 48105, USA
Mol Vis 9:14-7. 2003..To determine if mutations in the retinal transcription factor gene NRL are associated with retinopathies other than autosomal dominant retinitis pigmentosa (adRP)... - Evaluation of complex inheritance involving the most common Bardet-Biedl syndrome locus (BBS1)Kirk Mykytyn
Department of Pediatrics, Division of Medical Genetics, and Howard Hughes Medical Institute, University of Iowa, Iowa City, IA, 52242, USA
Am J Hum Genet 72:429-37. 2003..We show that the BBS1 gene is highly conserved between mice and humans. Finally, we demonstrate that BBS1 is inherited in an autosomal recessive manner and is rarely, if ever, involved in complex inheritance... - Blinded by the lightSamuel G Jacobson
Nat Genet 32:215-6. 2002 - QRX, a novel homeobox gene, modulates photoreceptor gene expressionQing Liang Wang
McKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Hum Mol Genet 13:1025-40. 2004..In addition, the finding of rare heterozygous QRX sequence changes in three individuals with retinal degeneration raises the possibility that QRX may be involved in disease pathogenesis... - Biochemical characterisation of the C1QTNF5 gene associated with late-onset retinal degeneration. A genetic model of age-related macular degenerationXinhua Shu
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK
Adv Exp Med Biol 572:41-8. 2006 - Usher syndrome type III: revised genomic structure of the USH3 gene and identification of novel mutationsRandall R Fields
Center for the Study and Treatment of Usher Syndrome, Boys Town National Research Hospital Omaha, NE, 68131, USA
Am J Hum Genet 71:607-17. 2002..We have also identified mouse (chromosome 3) and rat (chromosome 2) orthologues, as well as two human paralogues on chromosomes 4 and 10... - Outcome measures and their application in clinical trials for retinal degenerative diseases: outline, review, and perspectiveGerald A Fishman
Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, Illinois, USA
Retina 25:772-7. 2005 - Lifespan and mitochondrial control of neurodegenerationAlan F Wright
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK
Nat Genet 36:1153-8. 2004..This provides a new and unifying framework for investigating neurodegenerative disorders... - Evidence for retinal remodelling in retinitis pigmentosa caused by PDE6B mutationSamuel G Jacobson
Br J Ophthalmol 91:699-701. 2007
Research Grants
- PATHOGENESIS OF RETINAL DEGENERATIONSSamuel Jacobson; Fiscal Year: 2001..The results of this research will lead to the formulation of hypotheses about the underlying molecular events in these diseases and may evolve into recommendations for treatment paradigms in these blinding retinal degenerations. ..
- Clinical trials of gene therapy for Leber congenital amaurosisSamuel Jacobson; Fiscal Year: 2007....
- Early-onset retinal degenerationsSamuel Jacobson; Fiscal Year: 2005....