Abstract

Age-related macular degeneration (AMD) is the most common cause of severe visual loss in the developed world, affecting more than 10 million people in the United States alone. Approximately 1 in 3 people over the age of 75 are affected to some degree. A significant fraction of this disease is genetic, with major genetic risk factors on chromosomes 1 and 10. In this study, we will take advantage of molecular genetics, state of the art computer-assisted image analysis, large patient populations, well characterized donor eye tissue, induced pluripotent stem cells and CRISPR based genome editing to determine the molecular basis of how variations in AMD loci increase risk of AMD. These studies will provide new insight into the pathophysiologic mechanisms of AMD that will be valuable for the development of more specific diagnostic methods and more effective therapies.

Public Health Relevance

Age-related macular degeneration (AMD) is the most common cause of heritable blindness in the developed world. In this research study we will investigate the mechanism by which genetic mutations cause AMD in patients, donated eyes, and stem cells, so that more specific diagnostic methods and better treatments can be developed.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY026087-01A1
Application #
9174310
Study Section
Diseases and Pathophysiology of the Visual System Study Section (DPVS)
Program Officer
Shen, Grace L
Project Start
2016-09-01
Project End
2020-08-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
1
Fiscal Year
2016
Total Cost
$495,753
Indirect Cost
$170,669

  Institution

Name
University of Iowa
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
062761671
City
Iowa City
State
IA
Country
United States
Zip Code
52246

  Publications

Mullins, Robert F; McGwin Jr, Gerald; Searcey, Karen et al. (2018) The ARMS2 A69S Polymorphism Is Associated with Delayed Rod-Mediated Dark Adaptation in Eyes at Risk for Incident Age-Related Macular Degeneration. Ophthalmology :
Chirco, Kathleen R; Lewis, Carly J; Scheetz, Todd E et al. (2018) Evaluation of sFLT1 protein levels in human eyes with the FLT1 rs9943922 polymorphism. Ophthalmic Genet 39:68-72
Chirco, Kathleen R; Flamme-Wiese, Miles J; Wiley, Jill S et al. (2018) Evaluation of serum and ocular levels of membrane attack complex and C-reactive protein in CFH-genotyped human donors. Eye (Lond) 32:1740-1742
Songstad, Allison E; Worthington, Kristan S; Chirco, Kathleen R et al. (2017) Connective Tissue Growth Factor Promotes Efficient Generation of Human Induced Pluripotent Stem Cell-Derived Choroidal Endothelium. Stem Cells Transl Med 6:1533-1546