1273: Molecular Ophthalmology of Progressive Retinal Atrophy

Grant Status: Closed

Grant Amount: $219,874
Gustavo D. Aguirre, VMD, PhD; Cornell University
July 28, 1997 - July 27, 2000


Breed(s): Briard, Siberian Husky, Samoyed
Research Program Area: Ophthalmology
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Project Summary

The major aim of this project was to identify genes responsible for the different breed-specific forms of progressive retinal atrophy (PRA) and related diseases. In order to accomplish this, researchers laid important groundwork by identifying and cloning many of the genes that are present in the retina and known to cause disease in other species. Major accomplishments of this project included identifying the gene and the specific mutation that causes congenital stationary night blindness in Briards. As a result, a genetic test was developed for this recessive gene and now carriers can be identified and bred to normal dogs without producing affected progeny. Subsequent to the identification of this gene, gene therapy researchers at the University of Pennsylvania inserted this gene into the eyes of blind puppies and restored their sight. This is the first time this therapy has been successful in a mammal larger than a mouse. This finding may also have gene therapy potential for application in blind children. In addition, the researchers mapped the gene that causes X-linked PRA in Samoyeds and Siberian Huskies. This groundbreaking work allowed the development of a DNA test to identify carriers.


Aguirre, G D, Baldwin, V., Weeks, K. M., Acland, G. M., & Ray, K. (1999). Frequency of the Codon 807 Mutation in the cGMP Phosphodiesterase ?-Subunit Gene in Irish Setters and Other Dog Breeds with Hereditary Retinal Degeneration. The Journal of Heredity, 90(1), 143–147. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/9987922
Aguirre, Gustavo D, Baldwin, V., Pearce-Kelling, S., & NarfstrÃ, K. (n.d.). Congenital Stationary Night Blindness in the Dog: Common Mutation in the RPE65 Gene Indicates Founder Effect. Molecular Vision, 4(23). Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/9808841
Akhmedov, N B, Piriev, N. I., Pearce-Kelling, S., Acland, G. M., Aguirre, G., & Farber, D. (1998). Canine cone transducin-γ gene and cone degeneration in the cd dog. Investigative Ophthalmology & Visual Science, 39, 1775–1781. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/9727399
Akhmedov, Novrouz B, Baldwin, V., Zangerl, B., Kijas, J. K., Hunter, L. S., Minoofar, K. D., … Aguirre, G. D. (2002). Cloning and Characterization of the Canine Photoreceptor Specific Cone-Rod Homeobox (CRX) Gene and Evaluation as a Candidate for Early Onset Photoreceptor Diseases in the Dog. Molecular Vision, 8, 79–84. Retrieved from http://www.molvis.org/molvis/v8/a11/
Gu, W. (1999). Individual DNA bands obtained by RAPD analysis of canine genomic DNA often contain multiple DNA sequences. Journal of Heredity, 90(1), 96–98. https://doi.org/10.1093/jhered/90.1.96
Gu, Weikuan, & Ray, K. (1998). Detection of Single-Nucleotide Polymorphism. BioTechniques, 24, 836–837.
Ray, K. (1999). Strategies for identification of mutations causing hereditary retinal diseases in dogs: Evaluation of opsin as a candidate gene. Journal of Heredity, 90(1), 133–137. https://doi.org/10.1093/jhered/90.1.133
Wang, W., Acland, G. M., Ray, K., & Aguirre, G. D. (1999). Evaluation of cGMP-Phosphodiesterase (PDE) Subunits for Causal Association with Rod–Cone Dysplasia 2 (rcd2), a Canine Model of Abnormal Retinal cGMP Metabolism. Experimental Eye Research, 69(4), 445–453. https://doi.org/10.1006/exer.1999.0720
Zeiss, C. J. (2000). Mapping of X-linked progressive retinal atrophy (XLPRA), the canine homolog of retinitis pigmentosa 3 (RP3). Human Molecular Genetics, 9(4), 531–537. https://doi.org/10.1093/hmg/9.4.531
Zeiss, C. J, Acland, G. M., Aguirre, G. D., & Kunal Ray. (1998). TIMP-1 expression is increased in X-linked progressive retinal atrophy despite its exclusion as a candidate gene. Gene, 225(1–2), 67–75. https://doi.org/10.1016/S0378-1119(98)00521-6
Zeiss, C. J., Aguirre, G. D., & Ray, K. (1998). A highly polymorphic RFLP marker in the canine retinitis pigmentosa GTPase regulator (RPGR) gene. Animal Genetics, 29(5), 409.
Zeiss, C. J., Trepanier, L. A., Aguirre, G. D., & Ray, K. (1998). A highly conserved microsatellite in the dystrophin gene of diverse mammalian species. Animal Genetics, 29(3), 224–227.
Zeiss, Caroline J, Acland, G. M., & Aguirre, G. D. (1999). Retinal Pathology of Canine X-linked Progressive Retinal Atrophy, the Locus Homologue of RP3. Investigative Ophthalmology & Visual Science, 40(13), 13.

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