Genotype phenotype associations in inherited retinal degeneration

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Abstract This is an application for a K99/R00 NIH Pathway to Independence award. I am a postdoctoral fellow at the Retina Foundation of the Southwest. With the help of my sponsor, David Birch, PhD, I am establishing myself as a young investigator in clinical research of inherited retinal disease. This K99 award will provide me with the support necessary to accomplish the following goals: (1) to become proficient at examination of retinal structure in people with retinitis pigmentosa; (2) to become an expert in patient testing skills and methodology; and (3) to obtain theoretical understanding of psychophysics. To achieve this, I have assembled an advisory team comprised of a primary sponsor, Dr. Birch, Scientific Director, who conducts patient-oriented research on genetic eye disease, and 3 advisors: Dr. Rand Spencer, a vitreo-retinal specialist at Texas Retina Associates; Dr. Joost Felius, an expert in biostatistical analysis and computer programming; and Dr. Donald Hood, who is an expert in mathematical modeling of the phototransduction cascade and specializes in retinal diseases and clinical testing. Retinitis pigmentosa is characterized by retinal degeneration primarily affecting rod photoreceptors. My research will focus on measuring rod function in patients with retinitis pigmentosa who have known genetic mutations to look for patterns of rod visual field loss in the peripheral retina (Aim 1) and compare this novel method of evaluating rod function with traditional measures of rod function (Aim 2). Finally, studies comparing anatomical features with psychophysical testing will be performed (Aim 3). I will use the existing Southwest Eye Registry database at the Retina Foundation of the Southwest to enroll and track degenerative changes in 50 patients with retinitis pigmentosa who have known genetic mutations. In Aim 1, I will determine if a newly- developed wide-field, dark-adapted, two-color perimeter is reliable and if patients with RP have distinctive rod- mediated visual field loss. Aim 2 will identify the most sensitive and reliable method of monitoring rod function over time in retinitis pigmentosa and Aim 3 will relate photoreceptor function with corresponding locations of retinal structure. This research will form the basis of future measures of rod function and will generate the data that will be used for an RO1 grant application before the end of the R00 award.