This application's purpose is to make available to the research community certain canine strains affected with hereditary retinal degenerations, in order to facilitate research into the causes and cures of such diseases in people. This resource project, continuously managed by the principal investigators for the past 20 years, has 3 broad aspects. The first is to serve as a center for production and distribution, primarily to other independent research investigators, of 5 canine mutant models of hereditary retinal degenerations affecting humans. The need for these animals in research is addressed, as is the importance of maintaining them in a centralized breeding and distribution facility. The second objective is to continue collaborative studies already established to clone the genes for these diseases, investigate the cellular and molecular biology of these diseases, and develop methods for therapeutic intervention. The third aspect is to make available the physical and personnel resources supported by this project for instituting and conducting therapeutic trials as initiated by independent research investigators, either from academic or industrial organizations. Each such collaborative study is peer reviewed, separately, as part of the collaborative investigators' research protocols. Five strains of dogs, each transmitting a different gene for well characterized hereditary retinal degenerations (rod-cone dysplasia type 1 rcdl, progressive rod-cone degeneration prcd, early retinal degeneration erd, cone degeneration cd, and the newly available RPE65 mutant dog strain), together with appropriate nonaffected control dogs, will be bred and maintained. The progeny of these dogs will be distributed to research investigators, either directly or by collection, processing and distribution of requested tissues. Utilization of these mutants will be promoted by solicitation of requests from investigators. Assistance will be offered to investigators in development and implementation of specific protocols for optimal utilization of these mutants. Specific collaborative research includes programs to: identify, clone, and characterize the gene in cd, erd, prcd, and rcdl; cd, erd and prcd; determine and compare the role of programmed cell death genes in cd, erd, prcd, and rcdl; define the cause of abnormalities in docosaehexanoic acid transport & metabolism in prcd and identify candidate genes responsible for these deficiencies; further develop therapies for hereditary retinal degenerations including vector mediated gene transfer into canine photoreceptors; photoreceptor and retinal pigment epithelial cell transplantation into canine retina; and application of a visual-prosthetic silicon chip retinal implant.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Application #
Study Section
Special Emphasis Panel (ZEY1-VSN (04))
Program Officer
Dudley, Peter A
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Cornell University
Veterinary Sciences
Schools of Veterinary Medicine
United States
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Guziewicz, Karina E; McTish, Emily; Dufour, Valerie L et al. (2018) Underdeveloped RPE Apical Domain Underlies Lesion Formation in Canine Bestrophinopathies. Adv Exp Med Biol 1074:309-315
Guziewicz, Karina E; Cideciyan, Artur V; Beltran, William A et al. (2018) BEST1 gene therapy corrects a diffuse retina-wide microdetachment modulated by light exposure. Proc Natl Acad Sci U S A 115:E2839-E2848
Cideciyan, Artur V; Sudharsan, Raghavi; Dufour, Valérie L et al. (2018) Mutation-independent rhodopsin gene therapy by knockdown and replacement with a single AAV vector. Proc Natl Acad Sci U S A 115:E8547-E8556
Miyadera, Keiko (2018) Mapping of Canine Models of Inherited Retinal Diseases. Adv Exp Med Biol 1074:257-264
Hardcastle, Alison J; Sieving, Paul A; Sahel, José-Alain et al. (2018) Translational Retinal Research and Therapies. Transl Vis Sci Technol 7:8
Sudharsan, Raghavi; Elliott, Michael H; Dolgova, Natalia et al. (2018) Photoreceptor Outer Segment Isolation from a Single Canine Retina for RPE Phagocytosis Assay. Adv Exp Med Biol 1074:593-601
Das, Rueben G; Marinho, Felipe Pompeo; Iwabe, Simone et al. (2017) Variabilities in retinal function and structure in a canine model of cone-rod dystrophy associated with RPGRIP1 support multigenic etiology. Sci Rep 7:12823
Yeh, Connie Y; Koehl, Kristin L; Harman, Christine D et al. (2017) Assessment of Rod, Cone, and Intrinsically Photosensitive Retinal Ganglion Cell Contributions to the Canine Chromatic Pupillary Response. Invest Ophthalmol Vis Sci 58:65-78
Sudharsan, Raghavi; Beiting, Daniel P; Aguirre, Gustavo D et al. (2017) Involvement of Innate Immune System in Late Stages of Inherited Photoreceptor Degeneration. Sci Rep 7:17897
Ye, Guo-Jie; Komáromy, András M; Zeiss, Caroline et al. (2017) Safety and Efficacy of AAV5 Vectors Expressing Human or Canine CNGB3 in CNGB3-Mutant Dogs. Hum Gene Ther Clin Dev 28:197-207

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