Samuel Jacobson

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. ncbi request reprint Safety of recombinant adeno-associated virus type 2-RPE65 vector delivered by ocular subretinal injection
    Samuel G Jacobson
    Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Ther 13:1074-84. 2006
  2. doi request reprint Retinal optogenetic therapies: clinical criteria for candidacy
    S G Jacobson
    Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Clin Genet 84:175-82. 2013
  3. pmc 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 mutants
    Samuel 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
  4. ncbi request reprint Disease expression of RP1 mutations causing autosomal dominant retinitis pigmentosa
    S G Jacobson
    Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, USA
    Invest Ophthalmol Vis Sci 41:1898-908. 2000
  5. pmc Identifying photoreceptors in blind eyes caused by RPE65 mutations: Prerequisite for human gene therapy success
    Samuel G Jacobson
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 102:6177-82. 2005
  6. ncbi request reprint Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination
    Samuel G Jacobson
    Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Hum Mol Genet 12:1073-8. 2003
  7. pmc Human cone photoreceptor dependence on RPE65 isomerase
    Samuel 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
  8. ncbi request reprint Nuclear receptor NR2E3 gene mutations distort human retinal laminar architecture and cause an unusual degeneration
    Samuel G Jacobson
    Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia 19104, USA
    Hum Mol Genet 13:1893-902. 2004
  9. ncbi request reprint Leber congenital amaurosis caused by an RPGRIP1 mutation shows treatment potential
    Samuel G Jacobson
    Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Ophthalmology 114:895-8. 2007
  10. ncbi request reprint RDH12 and RPE65, visual cycle genes causing leber congenital amaurosis, differ in disease expression
    Samuel G Jacobson
    Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Invest Ophthalmol Vis Sci 48:332-8. 2007

Research Grants

  1. Clinical trials of gene therapy for Leber congenital amaurosis
    Samuel Jacobson; Fiscal Year: 2007
  2. PATHOGENESIS OF RETINAL DEGENERATIONS
    Samuel Jacobson; Fiscal Year: 2001
  3. Early-onset retinal degenerations
    Samuel Jacobson; Fiscal Year: 2005

Detail Information

Publications82

  1. ncbi request reprint Safety of recombinant adeno-associated virus type 2-RPE65 vector delivered by ocular subretinal injection
    Samuel 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...
  2. doi request reprint Retinal optogenetic therapies: clinical criteria for candidacy
    S G Jacobson
    Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Clin Genet 84:175-82. 2013
    ....
  3. pmc 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 mutants
    Samuel 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...
  4. ncbi request reprint Disease expression of RP1 mutations causing autosomal dominant retinitis pigmentosa
    S 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)...
  5. pmc Identifying photoreceptors in blind eyes caused by RPE65 mutations: Prerequisite for human gene therapy success
    Samuel G Jacobson
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 102:6177-82. 2005
    ....
  6. ncbi request reprint Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination
    Samuel 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...
  7. pmc Human cone photoreceptor dependence on RPE65 isomerase
    Samuel 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
    ....
  8. ncbi request reprint Nuclear receptor NR2E3 gene mutations distort human retinal laminar architecture and cause an unusual degeneration
    Samuel 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...
  9. ncbi request reprint Leber congenital amaurosis caused by an RPGRIP1 mutation shows treatment potential
    Samuel 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...
  10. ncbi request reprint RDH12 and RPE65, visual cycle genes causing leber congenital amaurosis, differ in disease expression
    Samuel 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...
  11. ncbi request reprint Safety in nonhuman primates of ocular AAV2-RPE65, a candidate treatment for blindness in Leber congenital amaurosis
    Samuel 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...
  12. ncbi request reprint Remodeling of the human retina in choroideremia: rab escort protein 1 (REP-1) mutations
    Samuel 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...
  13. pmc Photoreceptor layer topography in children with leber congenital amaurosis caused by RPE65 mutations
    Samuel 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...
  14. doi request reprint Disease boundaries in the retina of patients with Usher syndrome caused by MYO7A gene mutations
    Samuel 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...
  15. pmc Retinal disease course in Usher syndrome 1B due to MYO7A mutations
    Samuel G Jacobson
    Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA
    Invest Ophthalmol Vis Sci 52:7924-36. 2011
    ....
  16. doi request reprint Human retinal disease from AIPL1 gene mutations: foveal cone loss with minimal macular photoreceptors and rod function remaining
    Samuel 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...
  17. doi request reprint Normal central retinal function and structure preserved in retinitis pigmentosa
    Samuel 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)...
  18. ncbi request reprint Novel mutation in the TIMP3 gene causes Sorsby fundus dystrophy
    Samuel 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...
  19. pmc Gene therapy for leber congenital amaurosis caused by RPE65 mutations: safety and efficacy in 15 children and adults followed up to 3 years
    Samuel 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...
  20. pmc Leber congenital amaurosis caused by Lebercilin (LCA5) mutation: retained photoreceptors adjacent to retinal disorganization
    Samuel 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...
  21. pmc Usher syndromes due to MYO7A, PCDH15, USH2A or GPR98 mutations share retinal disease mechanism
    Samuel 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...
  22. ncbi request reprint Phenotypic marker for early disease detection in dominant late-onset retinal degeneration
    S 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...
  23. pmc Defining the residual vision in leber congenital amaurosis caused by RPE65 mutations
    Samuel 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...
  24. ncbi request reprint Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype
    Sharon 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...
  25. doi request reprint Visual acuity in patients with Leber's congenital amaurosis and early childhood-onset retinitis pigmentosa
    Saloni 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...
  26. ncbi request reprint In utero gene therapy rescues vision in a murine model of congenital blindness
    Nadine 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...
  27. ncbi request reprint Clinicopathologic effects of mutant GUCY2D in Leber congenital amaurosis
    Ann 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...
  28. ncbi request reprint Retinal disease expression in Bardet-Biedl syndrome-1 (BBS1) is a spectrum from maculopathy to retina-wide degeneration
    Amir 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...
  29. ncbi request reprint Impairment of the transient pupillary light reflex in Rpe65(-/-) mice and humans with leber congenital amaurosis
    Tomas 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...
  30. ncbi request reprint Electroretinographic analyses of Rpe65-mutant rd12 mice: developing an in vivo bioassay for human gene therapy trials of Leber congenital amaurosis
    Alejandro 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...
  31. pmc 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 trial
    William 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...
  32. ncbi request reprint De novo mutation in the RP1 gene (Arg677ter) associated with retinitis pigmentosa
    Sharon 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...
  33. pmc Harmonin in the murine retina and the retinal phenotypes of Ush1c-mutant mice and human USH1C
    David 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...
  34. doi request reprint Retinal disease in Usher syndrome III caused by mutations in the clarin-1 gene
    Waldo 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...
  35. ncbi request reprint Spinocerebellar ataxia type 7 (SCA7) shows a cone-rod dystrophy phenotype
    Tomas S Aleman
    Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Exp Eye Res 74:737-45. 2002
    ....
  36. ncbi request reprint Quantifying rod photoreceptor-mediated vision in retinal degenerations: dark-adapted thresholds as outcome measures
    Alejandro J Roman
    Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Exp Eye Res 80:259-72. 2005
    ....
  37. doi request reprint Retinal disease in Rpe65-deficient mice: comparison to human leber congenital amaurosis due to RPE65 mutations
    Rafael 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...
  38. ncbi request reprint Macular pigment and lutein supplementation in choroideremia
    Jacque 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...
  39. ncbi request reprint Full-field stimulus testing (FST) to quantify visual perception in severely blind candidates for treatment trials
    Alejandro 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...
  40. pmc Retinal laminar architecture in human retinitis pigmentosa caused by Rhodopsin gene mutations
    Tomas 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...
  41. pmc Macular pigment and lutein supplementation in ABCA4-associated retinal degenerations
    Tomas 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...
  42. pmc Reduced-illuminance autofluorescence imaging in ABCA4-associated retinal degenerations
    Artur 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
    ....
  43. ncbi request reprint Mutations in ABCA4 result in accumulation of lipofuscin before slowing of the retinoid cycle: a reappraisal of the human disease sequence
    Artur 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...
  44. ncbi request reprint Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis
    Artur V Cideciyan
    Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Hum Mutat 28:1074-83. 2007
    ....
  45. ncbi request reprint Cone deactivation kinetics and GRK1/GRK7 expression in enhanced S cone syndrome caused by mutations in NR2E3
    Artur 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...
  46. pmc Human RPE65 gene therapy for Leber congenital amaurosis: persistence of early visual improvements and safety at 1 year
    Artur 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...
  47. pmc The nuclear receptor NR2E3 plays a role in human retinal photoreceptor differentiation and degeneration
    Ann 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...
  48. pmc In vivo dynamics of retinal injury and repair in the rhodopsin mutant dog model of human retinitis pigmentosa
    Artur 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...
  49. doi request reprint CERKL mutations cause an autosomal recessive cone-rod dystrophy with inner retinopathy
    Tomas 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...
  50. pmc Loss of cone photoreceptors caused by chromophore depletion is partially prevented by the artificial chromophore pro-drug, 9-cis-retinyl acetate
    Tadao 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...
  51. pmc ABCA4-associated retinal degenerations spare structure and function of the human parapapillary retina
    Artur 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...
  52. pmc Human gene therapy for RPE65 isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics
    Artur 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...
  53. pmc ABCA4 disease progression and a proposed strategy for gene therapy
    Artur 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...
  54. pmc Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutation
    Geoffrey 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)...
  55. pmc Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degeneration
    James 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...
  56. pmc Inner retinal abnormalities in X-linked retinitis pigmentosa with RPGR mutations
    Tomas 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...
  57. ncbi request reprint In vivo micropathology of Best macular dystrophy with optical coherence tomography
    Michael 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
    ....
  58. pmc Subconjunctivally implantable hydrogels with degradable and thermoresponsive properties for sustained release of insulin to the retina
    Gauri 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...
  59. ncbi request reprint Nonhuman primate models for diabetic ocular neovascularization using AAV2-mediated overexpression of vascular endothelial growth factor
    Corinna 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...
  60. ncbi request reprint Early age-related maculopathy and self-reported visual difficulty in daily life
    Kay 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
    ....
  61. pmc In vivo function of the orphan nuclear receptor NR2E3 in establishing photoreceptor identity during mammalian retinal development
    Hong 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...
  62. pmc Retinal dystrophy due to paternal isodisomy for chromosome 1 or chromosome 2, with homoallelism for mutations in RPE65 or MERTK, respectively
    Debra 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
    ....
  63. pmc Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosa
    James 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...
  64. pmc A comprehensive mutation analysis of RP2 and RPGR in a North American cohort of families with X-linked retinitis pigmentosa
    Debra 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...
  65. pmc Lentiviral expression of retinal guanylate cyclase-1 (RetGC1) restores vision in an avian model of childhood blindness
    Melissa L Williams
    Department of Neuroscience, University of Florida McKnight Brain Institute, Gainesville, Florida, USA
    PLoS Med 3:e201. 2006
    ..The GUCY1*B chicken, which carries a null mutation in the retGC1 gene, is blind at hatching and serves as an animal model for the study of LCA1 pathology and potential treatments in humans...
  66. ncbi request reprint Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome
    Kirk 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...
  67. ncbi request reprint Blinded by the light
    Samuel G Jacobson
    Nat Genet 32:215-6. 2002
  68. pmc 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...
  69. ncbi request reprint Retinal degeneration associated with RDH12 mutations results from decreased 11-cis retinal synthesis due to disruption of the visual cycle
    Debra 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...
  70. ncbi request reprint Characterization of Usher syndrome type I gene mutations in an Usher syndrome patient population
    Xiao 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...
  71. ncbi request reprint CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia
    Susanne 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...
  72. ncbi request reprint Mutation analysis of NR2E3 and NRL genes in Enhanced S Cone Syndrome
    Alan F Wright
    MRC Human Genetics Unit, Western General Hospital, Edinburgh, United Kingdom
    Hum Mutat 24:439. 2004
    ....
  73. ncbi request reprint QRX, a novel homeobox gene, modulates photoreceptor gene expression
    Qing 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...
  74. ncbi request reprint 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 degeneration
    Caroline 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...
  75. pmc ABCA4 gene analysis in patients with autosomal recessive cone and cone rod dystrophies
    Veronique B D Kitiratschky
    Institute for Ophthalmic Research, Centre for Ophthalmology, University Tübingen, Tubingen, Germany
    Eur J Hum Genet 16:812-9. 2008
    ....
  76. ncbi request reprint Mutation screening of patients with Leber Congenital Amaurosis or the enhanced S-Cone Syndrome reveals a lack of sequence variations in the NRL gene
    Ceren 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)...
  77. pmc Long-term restoration of rod and cone vision by single dose rAAV-mediated gene transfer to the retina in a canine model of childhood blindness
    Gregory 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...
  78. pmc Evidence for retinal remodelling in retinitis pigmentosa caused by PDE6B mutation
    Samuel G Jacobson
    Br J Ophthalmol 91:699-701. 2007
  79. ncbi request reprint Biochemical characterisation of the C1QTNF5 gene associated with late-onset retinal degeneration. A genetic model of age-related macular degeneration
    Xinhua Shu
    MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK
    Adv Exp Med Biol 572:41-8. 2006
  80. ncbi request reprint Lifespan and mitochondrial control of neurodegeneration
    Alan 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...
  81. ncbi request reprint Outcome measures and their application in clinical trials for retinal degenerative diseases: outline, review, and perspective
    Gerald A Fishman
    Department of Ophthalmology and Visual Sciences, University of Illinois, Chicago, Illinois, USA
    Retina 25:772-7. 2005
  82. pmc Usher syndrome type III: revised genomic structure of the USH3 gene and identification of novel mutations
    Randall 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...

Research Grants14

  1. Clinical trials of gene therapy for Leber congenital amaurosis
    Samuel Jacobson; Fiscal Year: 2007
    ....
  2. PATHOGENESIS OF RETINAL DEGENERATIONS
    Samuel 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. ..
  3. Early-onset retinal degenerations
    Samuel Jacobson; Fiscal Year: 2005
    ....