Age-related macular degeneration (AMD) is the leading cause of severe vision loss in patients over 50 years of age in the United States. Evidence suggests that heritable factors cause a significant fraction of AMD. Inherited macular dystrophies provide a useful model for the study of the interaction between the photoreceptor and retinal pigment epithelium (RPE) in macular disease. Clinically, inherited macular dystrophies appear to be primarily RPE diseases, but the discovery of causative genes has shown that in certain macular dystrophies, the defective proteins localize to the photoreceptors. While advances in genetics have been powerful in identifying the molecular causes of some macular diseases, the progression from molecular defects to vision loss remains poorly understood. Adaptive optics can play a major role in providing a view of disease progression at a cellular level in living patients, helping to fill the scientific void between genes and blindness. Our hypothesis is that photoreceptor degeneration precedes RPE cell death in certain macular dystrophies, while lipofuscin accumulation in the RPE is the first pathologic change in other macular dystrophies, including an important subset of age-related macular degeneration associated with mutations in the fibulin-5 gene. We will test this hypothesis by applying in vivo adaptive optics imaging of the photoreceptor and RPE cells in patients identified with genetic mutations known to cause specific macular dystrophies and in descendants of cuticular drusen patients who carry fibulin-5 gene mutations. The candidate will conduct this study by creating a collaboration between the Center for Visual Science at Rochester, using the high resolution, in vivo imaging capabilities of the Rochester Adaptive Optics Ophthalmoscope (David Williams, PhD, mentor), and the Molecular Ophthalmology Laboratory at the University of Iowa (Edwin Stone, MD, PhD, co-mentor). ? ?
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