Jean Bennett

Summary

Affiliation: University of Pennsylvania
Country: USA

Publications

  1. doi request reprint AAV2 gene therapy readministration in three adults with congenital blindness
    Jean Bennett
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 309 Stellar Chance Labs, 422 Curie Boulevard, Philadelphia, PA 19104, USA
    Sci Transl Med 4:120ra15. 2012
  2. pmc Pupillometric analysis for assessment of gene therapy in Leber Congenital Amaurosis patients
    Paolo Melillo
    Department of Ophthalmology, Second University of Naples, Naples, Italy
    Biomed Eng Online 11:40. 2012
  3. pmc Stable transgene expression in rod photoreceptors after recombinant adeno-associated virus-mediated gene transfer to monkey retina
    J Bennett
    Department of Ophthalmology, F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 96:9920-5. 1999
  4. ncbi request reprint Commentary: an aye for eye gene therapy
    Jean Bennett
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Hum Gene Ther 17:177-9. 2006
  5. ncbi request reprint Gene therapy for retinitis pigmentosa
    J Bennett
    FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, PA 19104 6069, USA
    Curr Opin Mol Ther 2:420-5. 2000
  6. pmc Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer
    Jeannette Bennicelli
    Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6069, USA
    Mol Ther 16:458-65. 2008
  7. ncbi request reprint Gene therapy for choroideremia: in vitro rescue mediated by recombinant adenovirus
    Vibha Anand
    Department of Ophthalmology, F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6069, USA
    Vision Res 43:919-26. 2003
  8. 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
  9. pmc Safety and efficacy of gene transfer for Leber's congenital amaurosis
    Albert M Maguire
    Scheie Eye Institute, University of Pennsylvania, USA
    N Engl J Med 358:2240-8. 2008
  10. 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

Research Grants

  1. Animal Model for a Hereditary Macular Degeneration
    Jean Bennett; Fiscal Year: 2002
  2. Gene Therapy for Inherited Retinal Degeneration
    Jean Bennett; Fiscal Year: 2003
  3. Animal Model for a Hereditary Macular Degeneration
    Jean Bennett; Fiscal Year: 2003
  4. Gene Therapy for Inherited Retinal Degeneration
    Jean Bennett; Fiscal Year: 2004
  5. Animal Model for a Hereditary Macular Degeneration
    Jean Bennett; Fiscal Year: 2004
  6. Gene Therapy for Inherited Retinal Degeneration
    Jean Bennett; Fiscal Year: 2005
  7. Gene Therapy for Inherited Retinal Degeneration
    Jean Bennett; Fiscal Year: 2006
  8. Gene Therapy for Inherited Retinal Degeneration
    Jean Bennett; Fiscal Year: 2007
  9. AAV-mediated gene correction in retina
    Jean Bennett; Fiscal Year: 2007
  10. Gene Therapy for Usher Syndrome (USH1C)
    Jean Bennett; Fiscal Year: 2007

Detail Information

Publications86

  1. doi request reprint AAV2 gene therapy readministration in three adults with congenital blindness
    Jean Bennett
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 309 Stellar Chance Labs, 422 Curie Boulevard, Philadelphia, PA 19104, USA
    Sci Transl Med 4:120ra15. 2012
    ....
  2. pmc Pupillometric analysis for assessment of gene therapy in Leber Congenital Amaurosis patients
    Paolo Melillo
    Department of Ophthalmology, Second University of Naples, Naples, Italy
    Biomed Eng Online 11:40. 2012
    ....
  3. pmc Stable transgene expression in rod photoreceptors after recombinant adeno-associated virus-mediated gene transfer to monkey retina
    J Bennett
    Department of Ophthalmology, F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, 51 North 39th Street, Philadelphia, PA 19104, USA
    Proc Natl Acad Sci U S A 96:9920-5. 1999
    ..The findings further characterize the retinal cell tropism of rAAV. They also support the development of studies aimed ultimately at treating inherited retinal degeneration by using rAAV-mediated gene therapy...
  4. ncbi request reprint Commentary: an aye for eye gene therapy
    Jean Bennett
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Hum Gene Ther 17:177-9. 2006
  5. ncbi request reprint Gene therapy for retinitis pigmentosa
    J Bennett
    FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, PA 19104 6069, USA
    Curr Opin Mol Ther 2:420-5. 2000
    ..While much more progress needs to be made before moving from the laboratory to the clinic, gene therapy now holds much promise for slowing or even preventing blindness due to RP...
  6. pmc Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer
    Jeannette Bennicelli
    Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6069, USA
    Mol Ther 16:458-65. 2008
    ..The data demonstrate that AAV2.RPE65 delivers the RPE65 transgene efficiently and quickly to the appropriate target cells in vivo in animal models. This vector holds great promise for treatment of LCA due to RPE65 mutations...
  7. ncbi request reprint Gene therapy for choroideremia: in vitro rescue mediated by recombinant adenovirus
    Vibha Anand
    Department of Ophthalmology, F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104 6069, USA
    Vision Res 43:919-26. 2003
    ..Adenovirus-mediated delivery of REP-1 rescued the defective cells as assessed through protein and enzymatic assays. Ultimately, it may be possible to use virus-mediated delivery of REP-1 to evaluate disease intervention in vivo...
  8. 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...
  9. pmc Safety and efficacy of gene transfer for Leber's congenital amaurosis
    Albert M Maguire
    Scheie Eye Institute, University of Pennsylvania, USA
    N Engl J Med 358:2240-8. 2008
    ..Although the follow-up was very short and normal vision was not achieved, this study provides the basis for further gene therapy studies in patients with LCA...
  10. 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...
  11. doi request reprint Age-dependent effects of RPE65 gene therapy for Leber's congenital amaurosis: a phase 1 dose-escalation trial
    Albert M Maguire
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Lancet 374:1597-605. 2009
    ..We therefore did a phase 1 trial to assess the effect of gene therapy on retinal and visual function in children and adults with Leber's congenital amaurosis...
  12. ncbi request reprint Effect of over-expression of pigment epithelium derived factor (PEDF) on developing retinal vasculature in the mouse
    Wai T Wong
    F M Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia 19104 6069, USA
    Mol Vis 10:837-44. 2004
    ..This study aimed to determine whether over-expression of pigment epithelium derived factor alters the normal pattern of retinal vessel development...
  13. ncbi request reprint Long-term inducible gene expression in the eye via adeno-associated virus gene transfer in nonhuman primates
    Corinna Lebherz
    Gene Therapy Program, Department of Medicine, Division of Medical Genetics, University of Pennsylvania, Philadelphia, PA 19104, USA
    Hum Gene Ther 16:178-86. 2005
    ..5 years. The expression profiles were characterized by minimal basal expression in the absence of inducer and dose-responsive maximal expression in the presence of inducer drug...
  14. ncbi request reprint Systemic but not intraocular Epo gene transfer protects the retina from light-and genetic-induced degeneration
    Tonia S Rex
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Ther 10:855-61. 2004
    ..In conclusion, our data support Epo as a neuroprotective agent in some, but not all, retinal degenerations. Further, rescue is observed in specific models after systemic but not intraocular Epo gene transfer...
  15. ncbi request reprint Systemic rapamycin inhibits retinal and choroidal neovascularization in mice
    Nadine S Dejneka
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA
    Mol Vis 10:964-72. 2004
    ..VEGF plays a significant role in neovascular pathologies of the eye, thus we tested the possibility of using rapamycin to inhibit retinal and choroidal neovascularization (CNV)...
  16. doi request reprint Safety and efficacy of subretinal readministration of a viral vector in large animals to treat congenital blindness
    Defne Amado
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Sci Transl Med 2:21ra16. 2010
    ..Thus, subretinal readministration of rAAV2 in animals is safe and effective, even in the setting of preexisting immunity to the vector, a parameter that has been used to exclude patients from gene therapy trials...
  17. 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
    ....
  18. 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...
  19. ncbi request reprint The distribution, concentration, and toxicity of enhanced green fluorescent protein in retinal cells after genomic or somatic (virus-mediated) gene transfer
    Tonia S Rex
    F M Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Vis 11:1236-45. 2005
    ..The concentration of enhanced green fluorescent protein (EGFP) in individual photoreceptor cells of live mouse retina was quantified and correlated with physiological measurements of cell function...
  20. pmc Delivery of adeno-associated virus vectors to the fetal retina: impact of viral capsid proteins on retinal neuronal progenitor transduction
    Enrico M Surace
    F M Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, Scheie Eye Institute, 310 Stellar Chance Building, University of Pennsylvania, 422 Curie Boulevard, Philadelphia, PA 19104 6069, USA
    J Virol 77:7957-63. 2003
    ..The procedure is not detrimental to retinal development and function and therefore provides a safe delivery vehicle for potential therapeutic applications and a means of assessing the mechanisms of retina development and disease...
  21. pmc The human visual cortex responds to gene therapy-mediated recovery of retinal function
    Manzar Ashtari
    Diffusion Tensor Image Analyses and Brain Morphometry Center, Department of Radiology, Children s Hospital of Philadelphia CHOP, Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 121:2160-8. 2011
    ..In addition, these data suggest that gene therapy resulted in not only sustained and improved visual ability, but also enhanced contrast sensitivity...
  22. 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...
  23. 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...
  24. ncbi request reprint Light damage induced changes in mouse retinal gene expression
    Lin Chen
    F M Kirby Center for Molecular Ophthalmology Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Exp Eye Res 79:239-47. 2004
    ..The genes found upregulated by light damage may affect the survival of photoreceptors subjected to photo-oxidative stress...
  25. 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...
  26. pmc Novel AAV serotypes for improved ocular gene transfer
    Corinna Lebherz
    Gene Therapy Program, Division of Medical Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA
    J Gene Med 10:375-82. 2008
    ..We show here that AAV7 and 8 enable superior long-term transduction of retinal and also anterior chamber structures...
  27. 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...
  28. ncbi request reprint Persistent fetal ocular vasculature in mice deficient in bax and bak
    Paul Hahn
    Departments of Medicine, Pathology, and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, USA
    Arch Ophthalmol 123:797-802. 2005
    ..The ocular fetal vasculature normally regresses by apoptosis but for unknown reasons fails to regress in the human disease persistent fetal vasculature...
  29. pmc AAV9 targets cone photoreceptors in the nonhuman primate retina
    Luk H Vandenberghe
    Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 8:e53463. 2013
    ..We conclude AAV9 is an ideal candidate for strategies that require restoration of cone photoreceptor function...
  30. ncbi request reprint Gene transfer to ocular stem cells by early gestational intraamniotic injection of lentiviral vector
    Masayuki Endo
    The Children s Center for Fetal Research, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
    Mol Ther 15:579-87. 2007
    ..This model may be useful for the investigation of mechanisms of genetic and/or developmental ocular disease and for the development of prenatal gene therapy for specific ocular disorders...
  31. ncbi request reprint Spatial and temporal expression patterns of the choroideremia gene in the mouse retina
    Nicholas W Keiser
    Department of Ophthalmology, F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104 6069, USA
    Mol Vis 11:1052-60. 2005
    ..A study of the expression patterns of Chm and the related gene Chml in the mouse retina was undertaken in order to address this issue...
  32. ncbi request reprint Small interfering RNA (siRNA) targeting VEGF effectively inhibits ocular neovascularization in a mouse model
    Samuel J Reich
    F M Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia 19104, USA
    Mol Vis 9:210-6. 2003
    ..The purpose of this study was to demonstrate the feasibility of RNA interference mediated by siRNA in retinal cells in vitro and in the murine retina in vivo...
  33. ncbi request reprint Proapoptotic bcl-2 family members, Bax and Bak, are essential for developmental photoreceptor apoptosis
    Paul Hahn
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Philadelphia, Pennsylvania, USA
    Invest Ophthalmol Vis Sci 44:3598-605. 2003
    ..The purpose of this study was to characterize the roles in retinal development of the proapoptotic Bcl-2 family members Bax and Bak...
  34. ncbi request reprint Inhibition of retinal neovascularization by intraocular viral-mediated delivery of anti-angiogenic agents
    Alberto Auricchio
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Mol Ther 6:490-4. 2002
    ..All three vectors inhibited ischemia-induced neovascularization...
  35. ncbi request reprint AAV-mediated delivery of ciliary neurotrophic factor prolongs photoreceptor survival in the rhodopsin knockout mouse
    F Q Liang
    F. M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA
    Mol Ther 3:241-8. 2001
    ..This protection lasted through termination of the experiment (3 months). AAV-mediated delivery of CNTF may have implications for the treatment of human retinal degeneration...
  36. doi request reprint Dosage thresholds for AAV2 and AAV8 photoreceptor gene therapy in monkey
    Luk H Vandenberghe
    Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, and Center for Cellelar and Molecular Therapeutics, Children s Hospital of Philadelphia, Philadelphia, PA 19104, USA
    Sci Transl Med 3:88ra54. 2011
    ..These preclinical results provide guidance for optimal vector and dose selection in future human gene therapy trials to treat retinal diseases caused by loss of photoreceptors...
  37. ncbi request reprint Gene therapy for Leber congenital amaurosis
    Jean Bennett
    FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, 310 Stellar Chance Labs, 422 Curie Boulevard, Philadelphia, PA 19104 2689, USA
    Novartis Found Symp 255:195-202; discussion 202-7. 2004
    ..Preliminary results of studies in progress are described and the implications of these results with respect to developing human clinical trials for LCA and for other retinal degenerative diseases are discussed...
  38. ncbi request reprint In vivo delivery of recombinant viruses to the fetal murine cochlea: transduction characteristics and long-term effects on auditory function
    Jeffrey C Bedrosian
    FM Kirby Center and Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Mol Ther 14:328-35. 2006
    ..AAV2/1 promises to be useful in further studies evaluating differentiation pathways of cochlear cells in health and disease and for developing gene-based therapies for congenital and acquired forms of peripheral hearing loss...
  39. ncbi request reprint Adeno-associated viruses containing bFGF or BDNF are neuroprotective against excitotoxicity
    Frank Schuettauf
    Department of Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia, Pennsylvania, USA
    Curr Eye Res 29:379-86. 2004
    ..We tested the possibility of delivering these growth factors to retinal ganglion cells via an adeno-associated viral (AAV) vector and tested their efficacy in two models of excitotoxicity...
  40. ncbi request reprint Gene therapy for ocular neovascularization: a cure in sight
    Samuel J Reich
    FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, The University of Pennsylvania, 310 Stellar Chance Labs, 422 Curie Blvd, Philadelphia, Pennsylvania 19104 6069, USA
    Curr Opin Genet Dev 13:317-22. 2003
    ..A gene-therapy solution to the debilitating blindness caused by ocular neovascularization may be on the horizon...
  41. ncbi request reprint Phenotypic rescue after adeno-associated virus-mediated delivery of 4-sulfatase to the retinal pigment epithelium of feline mucopolysaccharidosis VI
    Thucanh T Ho
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA
    J Gene Med 4:613-21. 2002
    ..Retinal involvement is limited to the retinal pigment epithelium (RPE). This study aimed to determine whether recombinant adeno-associated virus (AAV)-mediated delivery of 4S would reverse the RPE pathology seen in MPS VI cats...
  42. ncbi request reprint Long-term protection of retinal structure but not function using RAAV.CNTF in animal models of retinitis pigmentosa
    F Q Liang
    F. M. Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Ther 4:461-72. 2001
    ..GFP. The discordance of functional and structural results, especially in the rat models, points to the need for a greater understanding of the mechanism of action of CNTF before human application can be considered...
  43. pmc Gene delivery to the retina: from mouse to man
    Jean Bennett
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania, USA
    Methods Enzymol 507:255-74. 2012
    ..The information presented here is designed to assist scientists and clinicians to use gene transfer to probe the biology of the retina and/or to move appropriate gene-based treatment studies from the bench to the clinic...
  44. ncbi request reprint Gene therapy for Leber congenital amaurosis
    Nadine S Dejneka
    University of Pennsylvania, Scheie Eye Institute, Philadelphia, PA 19104 6069, USA
    Adv Exp Med Biol 533:415-22. 2003
  45. pmc Imaging oxygen pressure in the rodent retina by phosphorescence lifetime
    David F Wilson
    Department of Biochemistry, Medical School, University of Pennsylvania, Philadelphia 19104, USA
    Adv Exp Med Biol 578:119-24. 2006
  46. ncbi request reprint A deviant immune response to viral proteins and transgene product is generated on subretinal administration of adenovirus and adeno-associated virus
    Vibha Anand
    Univeristy of Pennsylvania, F M Kirby Center for Molecular Ophthalmology, 310 Stellar Chance Labs, Scheie Eye Institute, 422 Curie Blvd, Philadelphia, Pennsylvania 19104 6069, USA
    Mol Ther 5:125-32. 2002
    ..This subsequently generates a population of immunosuppressive Th2-type, cytokine-secreting, splenic T cells. This response may be advantageous to the development of ocular gene therapy...
  47. pmc Tie2Cre-mediated inactivation of plexinD1 results in congenital heart, vascular and skeletal defects
    Ying Zhang
    Department of Cell and Developmental Biology, Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Dev Biol 325:82-93. 2009
    ..These results demonstrate an important role for PlexinD1 in embryonic and adult vasculature...
  48. ncbi request reprint Pigment epithelium-derived factor expression in the developing mouse eye
    K C Behling
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia 19104 6069, USA
    Mol Vis 8:449-54. 2002
    ..Because of the potential importance of normal PEDF expression patterns in controlling ocular blood vessel growth in health and disease, we characterized these patterns over the period of retinal vascular development in the mouse...
  49. ncbi request reprint Pharmacological regulation of protein expression from adeno-associated viral vectors in the eye
    Alberto Auricchio
    Institute for Human Gene Therapy, The Wistar Institute, Department of Molecular and Cellular Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Mol Ther 6:238-42. 2002
    ..The rapamycin inducible system promises to be useful for developing gene therapies for inherited retinal degeneration and ocular neovascularization...
  50. ncbi request reprint Exchange of surface proteins impacts on viral vector cellular specificity and transduction characteristics: the retina as a model
    A Auricchio
    Institute for Human Gene Therapy, Department of Molecular and Cellular Engineering, The Wistar Institute, Philadelphia, PA, USA
    Hum Mol Genet 10:3075-81. 2001
    ..We conclude that pseudotyping provides a useful means to manipulate viral vector cell targeting specificity as well as retinal transduction characteristics of vectors containing the same genome...
  51. ncbi request reprint Efficient trans-splicing in the retina expands the utility of adeno-associated virus as a vector for gene therapy
    S J Reich
    F M Kirby Center for Molecular Ophthalmology, Department of Ophthalmology, Scheie Eye Institute, Philadelphia, PA 19104, USA
    Hum Gene Ther 14:37-44. 2003
    ..The use of AAV2/5 also increases the efficiency of trans-splicing in photoreceptors. Selection of the appropriate AAV serotype is likely to affect efficiency of trans-splicing in other organ systems as well...
  52. pmc AAV-mediated gene therapy for choroideremia: preclinical studies in personalized models
    Vidyullatha Vasireddy
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 8:e61396. 2013
    ..The gene transfer is efficient and the preliminary safety data are encouraging. These studies pave the way for a human clinical trial of gene therapy for CHM...
  53. ncbi request reprint Retinal ganglion cell loss induced by acute optic neuritis in a relapsing model of multiple sclerosis
    Kenneth S Shindler
    Department of Ophthalmology, University of Pennsylvania, Scheie Eye Institute, 51 N 39th Street, Philadelphia, PA 19104, USA
    Mult Scler 12:526-32. 2006
    ..8% by day 18. No RGC loss occurred in eyes without optic neuritis. The fact that inflammation precedes RGC loss suggests that neuronal loss during optic neuritis occurs secondary to the inflammatory process...
  54. pmc Herpes simplex virus type 1 glycoprotein e is required for axonal localization of capsid, tegument, and membrane glycoproteins
    Fushan Wang
    Department of Medicine, Division of Infectious Diseases, 502 Johnson Pavilion, University of Pennsylvania, Philadelphia, PA 19104 6073, USA
    J Virol 79:13362-72. 2005
    ..The requirement for gE in axonal targeting and retrograde spread highlights intriguing similarities and differences between HSV-1 and pseudorabies virus gE...
  55. ncbi request reprint Gene therapy and animal models for retinal disease
    Nadine S Dejneka
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA
    Dev Ophthalmol 37:188-98. 2003
    ..We will describe the animal models used to study these disorders and emphasize the progress that has been made in using gene therapy for the treatment of retinal disease...
  56. pmc Oxygen distribution and vascular injury in the mouse eye measured by phosphorescence-lifetime imaging
    David F Wilson
    Department of Biochemistry, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Appl Opt 44:5239-48. 2005
    ..High-resolution maps of oxygen distribution in the retina can provide greater understanding of the role of oxygen and vascular function in diseases of the eye...
  57. ncbi request reprint Retinal progenitor cells--timing is everything
    Jean Bennett
    Scheie Eye Institute, University of Pennsylvania, Philadelphia, USA
    N Engl J Med 356:1577-9. 2007
  58. ncbi request reprint Photoreceptor cell rescue in retinal degeneration (rd) mice by in vivo gene therapy
    J Bennett
    Department of Ophthalmology, F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia 19104, USA
    Nat Med 2:649-54. 1996
    ..The findings demonstrate cell rescue by in vivo gene transfer, thus supporting the feasibility of treating an inherited retinal degeneration by somatic gene therapy...
  59. 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)...
  60. ncbi request reprint Localization of pigment epithelium derived factor (PEDF) in developing and adult human ocular tissues
    P C Karakousis
    F M Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA
    Mol Vis 7:154-63. 2001
    ..To localize pigment epithelium-derived factor (PEDF) in developing and adult human ocular tissues...
  61. ncbi request reprint Pharmacologically regulated gene expression in the retina following transduction with viral vectors
    N S Dejneka
    Department of Ophthalmology, Scheie Eye Institute, Institute for Human Gene Therapy, University of Pennsylvania, Philadelphia, PA 19104-6069, USA
    Gene Ther 8:442-6. 2001
    ..This mode of delivery and regulation offers a unique way to evaluate gene function in the eye and represents a novel method for introducing therapeutic proteins into the retina...
  62. 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...
  63. ncbi request reprint Dissecting the axoneme interactome: the mammalian orthologue of Chlamydomonas PF6 interacts with sperm-associated antigen 6, the mammalian orthologue of Chlamydomonas PF16
    Zhibing Zhang
    Center for Research on Reproduction and Women s Health and the Department of Ophthalmology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA
    Mol Cell Proteomics 4:914-23. 2005
    ..Thus, PF6, SPAG6, and PF20 form a newly identified network that links together components of the axoneme central apparatus and presumably participates in its dynamic regulation of ciliary and flagellar beat...
  64. ncbi request reprint Immune response following intraocular delivery of recombinant viral vectors
    J Bennett
    FM Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104 6069, USA
    Gene Ther 10:977-82. 2003
    ..Neither AAV nor lentivirus, however, elicit a cell-mediated response and are thus promising vectors for treatment of chronic ocular (retinal) diseases...
  65. doi request reprint Novel mathematical algorithm for pupillometric data analysis
    Matthew C Canver
    Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, United States F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, United States
    Comput Methods Programs Biomed 113:221-5. 2014
    ..Furthermore, it will be instrumental in the assessment of functional visual recovery in humans and pre-clinical models of retinal degeneration and optic nerve disease following pharmacological or gene-based therapies...
  66. doi request reprint Seeing the light
    Adam P Wojno
    F M Kirby Center for Molecular Ophthalmology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Sci Transl Med 5:175fs8. 2013
    ..One-time gene therapy resulted in multiyear visual improvement, and new approaches were used to evaluate effects on retinal structure...
  67. doi request reprint The bionic retina: a small molecule with big potential for visual restoration
    Theodore G Drivas
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Neuron 75:185-7. 2012
    ..Results show that, with the appropriate illumination, AAQ restores light sensitivity and visual behavior...
  68. ncbi request reprint Increased expression of ceruloplasmin in the retina following photic injury
    Lin Chen
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA, USA
    Mol Vis 9:151-8. 2003
    ..The purpose of this study was to determine whether retinal ceruloplasmin is upregulated following photo-oxidation, to localize ceruloplasmin protein, and to determine which ceruloplasmin isoform is present in the retina...
  69. 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...
  70. ncbi request reprint Adenovirus-mediated delivery of catalase to retinal pigment epithelial cells protects neighboring photoreceptors from photo-oxidative stress
    T S Rex
    F M Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA 19104, USA
    Hum Gene Ther 15:960-7. 2004
    ..The data provide a paradigm for antioxidant gene therapy with catalase, designed to protect not only transduced cells, but also neighboring cells...
  71. ncbi request reprint Gene therapy and retinitis pigmentosa: advances and future challenges
    N S Dejneka
    F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia 19104-6069, USA
    Bioessays 23:662-8. 2001
    ..Future challenges include confirming therapeutic effects in animal models with eyes more anatomically similar to those of humans and demonstrating long-term rescue with minimal toxicity...
  72. ncbi request reprint CEP290 and the primary cilium
    Theodore G Drivas
    Cell and Molecular Biology Department, 404 Anatomy and Chemistry, University of Pennsylvania Perelman School of Medicine, 3620 Hamilton Walk, 19104, Philadelphia, PA, USA
    Adv Exp Med Biol 801:519-25. 2014
    ..Here we discuss many of these diverse aspects of CEP290 biology and pathology in an attempt to link what we know about the molecular mechanisms of CEP290 function with what we know about CEP290-associated disease...
  73. pmc Adeno-Associated Virus-Mediated Gene Transfer to Renal Tubule Cells via a Retrograde Ureteral Approach
    Daniel C Chung
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA, USA
    Nephron Extra 1:217-23. 2011
    ..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...
  74. pmc Spectrum of mutations in the RPGR gene that are identified in 20% of families with X-linked retinitis pigmentosa
    M Buraczynska
    Department of Ophthalmology, W K Kellogg Eye Center, University of Michigan, Ann Arbor 48105, USA
    Am J Hum Genet 61:1287-92. 1997
    ..The reported studies will be beneficial in establishing genotype-phenotype correlations and should lead to further investigations seeking to understand the mechanism of disease pathogenesis...
  75. ncbi request reprint Strain-dependent anterior segment neovascularization following intravitreal gene transfer of basic fibroblast growth factor (bFGF)
    A R Gupta
    Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA
    J Gene Med 3:252-9. 2001
    ..Genetic modifiers may contribute to and/or prevent neovascularization induced by bFGF...
  76. ncbi request reprint Melatonin delays photoreceptor degeneration in the rds/rds mouse
    F Q Liang
    Department of Ophthalmology, Scheie Eye Institute, University of Pennsylvania School of Medicine, Philadelphia 19104, USA
    Neuroreport 12:1011-4. 2001
    ..Melatonin treatment significantly delayed photoreceptor loss and reduced the number of apoptotic photoreceptors. Further studies should determine if melatonin will have potential for the treatment of certain human retinal degenerations...
  77. ncbi request reprint Lateral connectivity and contextual interactions in macaque primary visual cortex
    Dan D Stettler
    The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Neuron 36:739-50. 2002
    ..These findings suggest that V1 intrinsic horizontal connections provide a more likely substrate for contour integration...
  78. 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...
  79. ncbi request reprint Imaging oxygen pressure in the retina of the mouse eye
    David F Wilson
    Adv Exp Med Biol 566:159-65. 2005
    ....
  80. ncbi request reprint Eye movement recordings as an effectiveness indicator of gene therapy in RPE65-deficient canines: implications for the ocular motor system
    Jonathan B Jacobs
    Daroff Dell Osso Ocular Motility Laboratory, Veterans Affairs Medical Center, Department of Neurology, Case Western Reserve University and University Hospital of Cleveland, OH 44106, USA
    Invest Ophthalmol Vis Sci 47:2865-75. 2006
    ..To perform ocular motility recordings of infantile nystagmus (IN) in RPE65-deficient canines and determine whether they can be used as a motor indicator of restored retinal function to investigate the effects of gene therapy...
  81. ncbi request reprint Müller cell transduction by AAV2 in normal and degenerative retinas
    Fong Qi Liang
    Retina Foundation of the Southwest, 9900 N Central Expressway, Suite 400, Dallas, TX 75231, USA
    Adv Exp Med Biol 533:439-45. 2003
  82. pmc Serotype-dependent packaging of large genes in adeno-associated viral vectors results in effective gene delivery in mice
    Mariacarmela Allocca
    Telethon Institute of Genetics and Medicine TIGEM, Naples, Italy
    J Clin Invest 118:1955-64. 2008
    ..The possibility of packaging large genes in AAV greatly expands the therapeutic potential of this vector system...
  83. ncbi request reprint Adeno-associated virus encoding green fluorescent protein as a label for retinal pigment epithelium
    Kathleen A Hansen
    Institute of Ophthalmology and Visual Science, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 01701, USA
    Invest Ophthalmol Vis Sci 44:772-80. 2003
    ..To determine whether transduction with adeno-associated virus encoding green fluorescent protein (AAV-GFP) is useful for labeling transplanted retinal pigment epithelial cells (RPE)...
  84. ncbi request reprint Strategies for delivery of rod-derived cone viability factor
    Jean Bennett
    Ophthalmology, Cell and Developmental Biology at the University of Pennsylvania School of Medicine in Philadelphia, PA, USA
    Retina 25:S47. 2005
  85. ncbi request reprint Accelerated mortality from hydrocephalus and pneumonia in mice with a combined deficiency of SPAG6 and SPAG16L reveals a functional interrelationship between the two central apparatus proteins
    Zhibing Zhang
    Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia 23298, USA
    Cell Motil Cytoskeleton 64:360-76. 2007
    ..The findings also demonstrate that SPAG6 and SPAG16L have related roles in controlling the function of cilia in the brain and lung...

Research Grants24

  1. Animal Model for a Hereditary Macular Degeneration
    Jean Bennett; Fiscal Year: 2002
    ..These studies aim to reveal specific biological pathways relevant to the pathology in this animal model. Any such pathways could potentially be manipulated in the future to slow/prevent the disease process. ..
  2. Gene Therapy for Inherited Retinal Degeneration
    Jean Bennett; Fiscal Year: 2003
    ..The ability to rescue photoreceptors in the PDEbeta or abcr -based animal models could ultimately pave the way for genetic therapy as a treatment for blinding retinal diseases. ..
  3. Animal Model for a Hereditary Macular Degeneration
    Jean Bennett; Fiscal Year: 2003
    ..These studies aim to reveal specific biological pathways relevant to the pathology in this animal model. Any such pathways could potentially be manipulated in the future to slow/prevent the disease process. ..
  4. Gene Therapy for Inherited Retinal Degeneration
    Jean Bennett; Fiscal Year: 2004
    ..The ability to rescue photoreceptors in the PDEbeta or abcr -based animal models could ultimately pave the way for genetic therapy as a treatment for blinding retinal diseases. ..
  5. Animal Model for a Hereditary Macular Degeneration
    Jean Bennett; Fiscal Year: 2004
    ..These studies aim to reveal specific biological pathways relevant to the pathology in this animal model. Any such pathways could potentially be manipulated in the future to slow/prevent the disease process. ..
  6. Gene Therapy for Inherited Retinal Degeneration
    Jean Bennett; Fiscal Year: 2005
    ..The ability to rescue photoreceptors in the PDEbeta or abcr -based animal models could ultimately pave the way for genetic therapy as a treatment for blinding retinal diseases. ..
  7. Gene Therapy for Inherited Retinal Degeneration
    Jean Bennett; Fiscal Year: 2006
    ..The ability to rescue photoreceptors in the PDEbeta or abcr -based animal models could ultimately pave the way for genetic therapy as a treatment for blinding retinal diseases. ..
  8. Gene Therapy for Inherited Retinal Degeneration
    Jean Bennett; Fiscal Year: 2007
    ..The ability to rescue photoreceptors in the PDEbeta or abcr -based animal models could ultimately pave the way for genetic therapy as a treatment for blinding retinal diseases. ..
  9. AAV-mediated gene correction in retina
    Jean Bennett; Fiscal Year: 2007
    ....
  10. Gene Therapy for Usher Syndrome (USH1C)
    Jean Bennett; Fiscal Year: 2007
    ....
  11. GENETIC THERAPY FOR HEREDITARY RETINAL DEGENERATIONS
    Jean Bennett; Fiscal Year: 2002
    ..The ability to rescue photoreceptors in the betaPDE or rhodopsin-based animal models could ultimately pave the way for genetic therapy as a treatment for blinding and currently incurable inherited retinal degenerations such as RP. ..
  12. GENETIC THERAPY FOR HEREDITARY RETINAL DEGENERATIONS
    Jean Bennett; Fiscal Year: 2001
    ..The ability to rescue photoreceptors in the betaPDE or rhodopsin-based animal models could ultimately pave the way for genetic therapy as a treatment for blinding and currently incurable inherited retinal degenerations such as RP. ..
  13. GENETIC THERAPY FOR HEREDITARY RETINAL DEGENERATIONS
    Jean Bennett; Fiscal Year: 1999
    ..The ability to rescue photoreceptors in the betaPDE or rhodopsin-based animal models could ultimately pave the way for genetic therapy as a treatment for blinding and currently incurable inherited retinal degenerations such as RP. ..
  14. ANIMAL MODELS FOR A HEREDITARY MACULAR DEGENERATON
    Jean Bennett; Fiscal Year: 1999
    ..The characterization of the pathogenic basis of SFD could suggest therapeutic approaches for treating this disease and other forms of macular degeneration. ..
  15. GENETIC THERAPY FOR HEREDITARY RETINAL DEGENERATIONS
    Jean Bennett; Fiscal Year: 2000
    ..The ability to rescue photoreceptors in the betaPDE or rhodopsin-based animal models could ultimately pave the way for genetic therapy as a treatment for blinding and currently incurable inherited retinal degenerations such as RP. ..
  16. ANIMAL MODELS FOR A HEREDITARY MACULAR DEGENERATON
    Jean Bennett; Fiscal Year: 2000
    ..The characterization of the pathogenic basis of SFD could suggest therapeutic approaches for treating this disease and other forms of macular degeneration. ..
  17. GENETIC THERAPY FOR HEREDITARY RETINAL DEGENERATIONS
    Jean Bennett; Fiscal Year: 2000
    ..The ability to rescue photoreceptors in the betaPDE or rhodopsin-based animal models could ultimately pave the way for genetic therapy as a treatment for blinding and currently incurable inherited retinal degenerations such as RP. ..
  18. Animal Model for a Hereditary Macular Degeneration
    Jean Bennett; Fiscal Year: 2001
    ..These studies aim to reveal specific biological pathways relevant to the pathology in this animal model. Any such pathways could potentially be manipulated in the future to slow/prevent the disease process. ..