The application proposes continuation of a resource project that has been continuously managed by the principal investigators for over 16 years. The project purpose has 2 parts. The first is to serve as a central research resource for production and distribution, to other independent research investigators, of 4 canine mutant models of the hereditary retinal degenerations affecting humans. The need for these canine mutants 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. Each such collaborative study is peer reviewed, separately, as part of the collaborative investigators' research protocols. Four strains of dogs, each transmitting a different gene for well characterized hereditary retinal degenerations (rod-cone dysplasia type 1 rcd1, progressive rod-cone degeneration prcd, early retinal degeneration erd, cone degeneration cd), 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 mutations for cd, erd and prcd; determine and compare the role of programmed cell death genes in cd,erd, prcd, and rcd1; define the cause of abnormalities in docosahexanoic 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 retinal implant.
| 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 |
Showing the most recent 10 out of 203 publications
