1. Medical College of Wisconsin Receives NIH Grant for Assessing Photoreceptor Structure and Function in Normal and Diseased Retinae

    Medical College of Wisconsin Receives NIH Grant for Assessing Photoreceptor Structure and Function in Normal and Diseased Retinae

    Medical College of Wisconsin Receives a 2017 NIH Grant for $545,415 for Assessing Photoreceptor Structure and Function in Normal and Diseased Retinae. The principal investigator is Josepth Carroll. The program began in 2008 and ends in 2021. Below is a summary of the proposed work.

    Inherited retinal degenerations affect approximately 1 in 1,500 individuals in the US, and given the extreme genotypic and phenotypic heterogeneity, the prospect of treating these devastating diseases is a formidable task. Nevertheless, trials examining novel therapeutic strategies are underway. An important key to success in the early phases of such trials is selection of patients with reasonable therapeutic potential – for example, a retina with no remaining cone photoreceptors would not be the best target for a gene therapy approach aiming to restore cone function. In addition, current clinical tools for assessing retinal structure are relatively insensitive and macroscopic, limiting the ability to monitor therapeutic response in these patients. As such, there is a need for sensitive, noninvasive, high-resolution techniques to assess photoreceptor structure. The Advanced Ocular Imaging Program has made significant advances on this front – advancing innovative adaptive-optics (AO) imaging instrumentation for probing photoreceptor inner- and outer-segment structure with single-cell resolution, creating software for extracting quantitative metrics of the photoreceptor mosaic, and developing tools for making accurate and reliable measurements of photoreceptor structure from optical coherence tomography (OCT) images of the retina. From a clinical perspective, these tools are in relative infancy, thus we propose to help accelerate their translation through the following specific aims: 1) Define the variability in the remnant cone population in human patients with achromatopsia (ACHM), 2) Characterize the integrity of the photoreceptor mosaic in individuals with L/M opsin mutations, and 3) Elucidate the rod/cone contribution to the photoreceptor layers in OCT images. The specific diseases being studied have a wide range of rod/cone involvement, are current or emerging targets for treatment efforts, and continue to represent a major strength of our multidisciplinary research team. This work is expected to have a significant positive impact, with the high-resolution genotype-phenotype relationships identified here providing a better understanding of the therapeutic potential in patients with inherited retinal degenerations as well as producing validated tools for assessing photoreceptor structure in emerging clinical trials. Our proposal addresses two emerging needs identified in the NEI Publication “Vision Research: Needs, Gaps, and Opportunities”: “Characterize the macula and perifoveal regions of the retina to better understand the predilection of the macula for disease,” and “Translate high-resolution retinal imaging technologies, like adaptive optics, into cost-effective and easy-to-use platforms for routine clinical use.”

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