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 Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY013203-02
Application #
6384918
Study Section
Visual Sciences C Study Section (VISC)
Program Officer
Dudley, Peter A
Project Start
2000-08-05
Project End
2004-07-31
Budget Start
2001-08-01
Budget End
2002-07-31
Support Year
2
Fiscal Year
2001
Total Cost
$198,125
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Beltran, William A; Cideciyan, Artur V; Boye, Shannon E et al. (2017) Optimization of Retinal Gene Therapy for X-Linked Retinitis Pigmentosa Due to RPGR Mutations. Mol Ther 25:1866-1880
Strauss, Rupert W; Ho, Alex; Muñoz, Beatriz et al. (2016) The Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) Studies: Design and Baseline Characteristics: ProgStar Report No. 1. Ophthalmology 123:817-28
Matsui, Rodrigo; McGuigan Iii, David B; Gruzensky, Michaela L et al. (2016) SPATA7: Evolving phenotype from cone-rod dystrophy to retinitis pigmentosa. Ophthalmic Genet 37:333-8
Cideciyan, Artur V; Swider, Malgorzata; Jacobson, Samuel G (2015) Autofluorescence imaging with near-infrared excitation:normalization by reflectance to reduce signal from choroidal fluorophores. Invest Ophthalmol Vis Sci 56:3393-406
Zhang, Ning; Tsybovsky, Yaroslav; Kolesnikov, Alexander V et al. (2015) Protein misfolding and the pathogenesis of ABCA4-associated retinal degenerations. Hum Mol Genet 24:3220-37
Matsui, Rodrigo; Cideciyan, Artur V; Schwartz, Sharon B et al. (2015) Molecular Heterogeneity Within the Clinical Diagnosis of Pericentral Retinal Degeneration. Invest Ophthalmol Vis Sci 56:6007-18
Beltran, William A; Cideciyan, Artur V; Iwabe, Simone et al. (2015) Successful arrest of photoreceptor and vision loss expands the therapeutic window of retinal gene therapy to later stages of disease. Proc Natl Acad Sci U S A 112:E5844-53
Cideciyan, Artur V; Swider, Malgorzata; Schwartz, Sharon B et al. (2015) Predicting Progression of ABCA4-Associated Retinal Degenerations Based on Longitudinal Measurements of the Leading Disease Front. Invest Ophthalmol Vis Sci 56:5946-55
Beltran, William A; Cideciyan, Artur V; Guziewicz, Karina E et al. (2014) Canine retina has a primate fovea-like bouquet of cone photoreceptors which is affected by inherited macular degenerations. PLoS One 9:e90390
Huang, Wei Chieh; Cideciyan, Artur V; Roman, Alejandro J et al. (2014) Inner and outer retinal changes in retinal degenerations associated with ABCA4 mutations. Invest Ophthalmol Vis Sci 55:1810-22

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