Genomes and Genes
VISUAL CYCLE IN HUMAN PHOTORECEPTOR AND RPE DISEASE
Principal Investigator: ARTUR CIDECIYAN
Affiliation: University of Pennsylvania
Abstract: DESCRIPTION (Adapted from applicant's abstract): Biochemical and physiological studies in vitro and in retina-specific ABC transporter (ABCR) -/- knockout mice suggest that ABCR accelerates recovery of rod photoreceptor resensitization after intense light exposure by transporting isomerized chromphore, all-trans-retinal, across the rod outer segment disk membrane. The current proposal is to test hypotheses about the role of ABCR in human disease as follows: (1) Study the visual cycle abnormalities in patients with retinopathy due to ABCR mutations with the goals of dissecting the contributions of primary rod effects vs. secondary disease consequences and learning the relationship between primary rod abnormalities and the genotype; (2) Investigate the basis of rod visual loss in these patients by testing the hypothesis that desensitization by equivalent light contributes to the visual loss, and determine if short term trial of unilateral light reduction can alter rod sensitivity and select mutations; (3) Test whether heterozygotes of ABCR mutations show visual cycle abnormalities and to approach from the visual function perspective the issue of ABCR sequence variance as risk factors in age related macular degeneration.
Funding Period: 2000-08-05 - 2005-01-31
more information: NIH RePORT
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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...
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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...
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Molecular Genetics Laboratory, Institute for Ophthalmic Research, Centre for Ophthalmology, University Tübingen, Tubingen, Germany
Invest Ophthalmol Vis Sci 49:5015-23. 2008..The present study was a comprehensive screening of the GUCY2D gene in 27 adCD and adCRD unrelated families of these rare disorders...
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Institute for Ophthalmic Research, Centre for Ophthalmology, University Tübingen, Tubingen, Germany
Eur J Hum Genet 16:812-9. 2008....
- 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....
- 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...
- 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...
- 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....
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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...