Hereditary retinal degenerations are an important cause of blindness in young people, and frequently are due to genetic abnormalities in photoreceptor cells of the retina. No current therapies exist to slow down progression of these diseases or to restore vision. This research seeks to understand the role of a specific gene, Arap1, which is required for healthy photoreceptor functioning. Determining the role of this gene in photoreceptors expands the basic understanding of retinal physiology, and also opens new avenues of potential therapy for this important group of our patient population who currently do not enjoy any beneficial therapies from modern medicine. This proposal seeks to determine how photoreceptor development and function is regulated, in particular by protein sorting, targeting and trafficking, with a focus on the most abundant, most important and best-studied protein in the outer segment, Rhodopsin (RHO). To study the role of RHO trafficking to the connecting cilium, we generated mice with a targeted deletion in the Arf GAP Arap1 from the U.C. Davis Knockout Mouse Project (KOMP). We have found that Arap1-/- mice exhibit features reminiscent of Retinitis Pigmentosa (RP) in humans: optic nerve pallor, vascular attenuation, pigmentary changes, and outer retinal thinning. The goal of this proposal is to define the natural history of this retinal degeneration, determine the molecular and cellular mechanisms underlying the photoreceptor damage, and to determine the suitability of this mouse as an animal model of recessive RP in humans. As an academic clinician-scientist and vitreoretinal specialist, I have both clinical and research interests in understanding the mechanisms of retinal diseases. With a strong background in retinal developmental biology and clinical treatment of retinal diseases, I am enthusiastically prepared to pursue basic and translational research to study the pathogenesis and treatment of hereditary retinal degenerations. UC Davis offers a world- class faculty and facilities that has the potential to facilitate my training in areas of molecular biology and biochemistry, live animal ocular imaging, and fundamental photoreceptor physiology. The mentoring and skills acquired with this grant proposal will enable me to attain expertise in translational hereditary retinal degeneration research.
Hereditary retinal degenerations are an important cause of blindness in young people, and frequently are due to genetic abnormalities in photoreceptor cells of the retina. No current therapies exist to slow down progression of these diseases or to restore vision. This research seeks to understand the role of a specific gene, Arap1, which is required for healthy photoreceptor functioning. Determining the role of this gene in photoreceptors expands the basic understanding of retinal physiology, and also opens new avenues of potential therapy for this important group of our patient population who currently do not enjoy any beneficial therapies from modern medicine.
| Moore, Bret A; Roux, Michel J; Sebbag, Lionel et al. (2018) A Population Study of Common Ocular Abnormalities in C57BL/6N rd8 Mice. Invest Ophthalmol Vis Sci 59:2252-2261 |
| Wong, Sophia S; Vuong, Vivian S; Cunefare, David et al. (2017) Macular Fluid Reduces Reproducibility of Choroidal Thickness Measurements on Enhanced Depth Optical Coherence Tomography. Am J Ophthalmol 184:108-114 |
| Moshiri, Ala; Humpal, Devin; Leonard, Brian C et al. (2017) Arap1 Deficiency Causes Photoreceptor Degeneration in Mice. Invest Ophthalmol Vis Sci 58:1709-1718 |
