This proposal addresses 2 of the program objectives of the NEI Retinal Diseases Panel: - "Explore the topographical and regional differences of the retina and the relationship of this topography to disease progression". - "Continue to develop and apply noninvasive technologies such as functional magnetic resonance imaging (fMRI), ocular coherence tomography, adaptive optics, and confocal imaging to better understand retinal function and changes in disease states". The overall purpose of this proposal is to characterize the topography of the cone mosaic in normal and diseased retinae, to examine the factors that might govern this topography, and to assess photoreceptor function in these mosaics. I have discovered novel cone degeneration mechanisms linked to mutations in the cone photopigments. The experiments in this proposal will help clarify the deleterious effects of disruptions in cone pigment expression, both on the appearance of the cone mosaic and on visual performance. This proposal is the first step in an effort to build a research program that will contribute to the understanding of fundamental biological processes underlying cone vision and vision disorders. By examining how topographical disruptions in the cone mosaic affect visual function (contrast sensitivity, acuity, sensitivity), I will gain novel insight into the structure-function relationship on a cellular level. Moreover, the methodological approach developed in this proposal will be translatable to other retinal diseases that are more complex in nature. Through a unique collaborative effort, I propose to combine psychophysical, electrophysiological, and genetic techniques with in vivo imaging techniques (such as optical coherence tomography &adaptive-optics ophthalmoscopy) to address the following aims:
Specific Aim 1 - Characterize the S-cone submosaic in normal and tritan subjects and its relationship to the overall topography of the retina.
Specific Aim 2 - Examine the effects of mutations in the L/M-photopigment gene array on the viability of the cones and the organization of the photoreceptor mosaic.
Specific Aim 3 - Determine the consequences of cone-opsin mutations and disorganization of the cone mosaic for cone and visual system function.
The majority of our visual activity relies on the cone photoreceptors in the retina. This proposal employs a multidisciplinary approach (using high-resolution retinal imaging, genetic analysis, and electrophysiological tests) to investigate how mutations in the cone pigments affect cone-photoreceptor structure &function. The work in this proposal will serve as the foundation for translation of this same approach to the future study of other retinal degenerations, which will accelerate progress for the effective implementation of novel therapies.
|Patterson, Emily J; Wilk, Melissa; Langlo, Christopher S et al. (2016) Cone Photoreceptor Structure in Patients With X-Linked Cone Dysfunction and Red-Green Color Vision Deficiency. Invest Ophthalmol Vis Sci 57:3853-63|
|Abozaid, Mortada A; Langlo, Christopher S; Dubis, Adam M et al. (2016) Reliability and Repeatability of Cone Density Measurements in Patients with Congenital Achromatopsia. Adv Exp Med Biol 854:277-83|
|Cooper, Robert F; Wilk, Melissa A; Tarima, Sergey et al. (2016) Evaluating Descriptive Metrics of the Human Cone Mosaic. Invest Ophthalmol Vis Sci 57:2992-3001|
|Langlo, Christopher S; Patterson, Emily J; Higgins, Brian P et al. (2016) Residual Foveal Cone Structure in CNGB3-Associated Achromatopsia. Invest Ophthalmol Vis Sci 57:3984-95|
|Cunefare, David; Cooper, Robert F; Higgins, Brian et al. (2016) Automatic detection of cone photoreceptors in split detector adaptive optics scanning light ophthalmoscope images. Biomed Opt Express 7:2036-50|
|Sun, Lynn W; Johnson, Ryan D; Langlo, Christopher S et al. (2016) Assessing Photoreceptor Structure in Retinitis Pigmentosa and Usher Syndrome. Invest Ophthalmol Vis Sci 57:2428-42|
|Cooper, Robert F; Sulai, Yusufu N; Dubis, Adam M et al. (2016) Effects of Intraframe Distortion on Measures of Cone Mosaic Geometry from Adaptive Optics Scanning Light Ophthalmoscopy. Transl Vis Sci Technol 5:10|
|Razeen, Moataz M; Cooper, Robert F; Langlo, Christopher S et al. (2016) Correlating Photoreceptor Mosaic Structure to Clinical Findings in Stargardt Disease. Transl Vis Sci Technol 5:6|
|Scoles, Drew; Sulai, Yusufu N; Cooper, Robert F et al. (2016) PHOTORECEPTOR INNER SEGMENT MORPHOLOGY IN BEST VITELLIFORM MACULAR DYSTROPHY. Retina :|
|Cooper, Robert F; Lombardo, Marco; Carroll, Joseph et al. (2016) Methods for investigating the local spatial anisotropy and the preferred orientation of cones in adaptive optics retinal images. Vis Neurosci 33:E005|
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