Best disease, or vitelliform macular dystrophy, is a human macular degenerative disorder characterized by progressive and irreversible central vision loss. The disease is caused by a host of different (largely missense) mutations in the gene BEST1. Currently there is no treatment or cure for this condition. In this multicenter, multi-PI proposal, we will evaluate the pathophysiology of Best disease using RPE cells derived from induced pluripotent stem cells (iPSCs) from patients with known BEST1 mutations. Preliminary data show that these cells recapitulate at least some the phenotypes of human RPE cells with Best disease. We propose multidisciplinary experiments that will lead to a better understanding of this blinding disease, and that include: determining the pathology of Best disease patient-derived RPE cell chloride conductance and cellular electrophysiology; determining the pathological relationship between different mutations, and between dominant and recessive forms of Best disease; and evaluating gene therapy/genome editing as a potential treatment for Best disease. These important studies will pave the way for new treatments for this disorder.

Public Health Relevance

Best disease (BD) is a human macular degenerative disorder characterized by progressive and irreversible central vision loss. The disease is caused by a host of different (largely missense) mutations in the gene BEST1. Currently there is no treatment or cure for this condition. We propose multidisciplinary experiments that will lead to a better understanding of this blinding disease and pave the way for new treatments for this disorder.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY024588-03
Application #
9310286
Study Section
Diseases and Pathophysiology of the Visual System Study Section (DPVS)
Program Officer
Neuhold, Lisa
Project Start
2015-09-01
Project End
2019-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
3
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Iowa
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52242
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