AAV Gene Augmentation Therapy Rescues the Phenotype in the RDH5−/− Cat Model of Fundus Albipunctatus
7 affiliations
- 1Genetics and Genome Sciences, Michigan State University, East Lansing, Michigan, United States
- 2Small Animal Clinical Sciences, Michigan State University, East Lansing, Michigan, United States
- 3Department of Physiology and Biophysics, University of California, Irvine, Irvine, California, United States
- 4Brunson Center for Translational Vision Research, Department of Ophthalmology and Visual Sciences, University of California, Irvine, Irvine, California, United States
- 5Ophthalmology Services, Charles River Laboratories, Mattawan, Michigan, United States
- 6Department of Clinical Pharmacy Practice, School of Pharmacy and Pharmaceutical Sciences, University of California, Irvine, Irvine, California, United States
- 7Research Service, VA Long Beach Healthcare System, Long Beach, California, United States
Abstract
Purpose: Retinol dehydrogenase 5 (RDH5) catalyzes the final oxidation for visual pigment regeneration of 11-cis-retinal as part of the visual cycle in the retinal pigment epithelium (RPE). In humans, RDH5 mutations cause fundus albipunctatus characterized by night blindness, accumulation of white-yellowish fundus spots, and, in a subset of patients, macular degeneration. Currently, there is an unmet need for therapies for patients with RDH5 mutations. Using a large-animal cat model of RDH5-associated disease (RDH5−/−), this study aimed to meet these needs through development of a gene augmentation therapy able to rescue RDH5-associated retinopathies.
Methods: An adeno-associated virus serotype 2 with triple capsid mutations vector packaged with feline RDH5 cDNA (AAV-VMD2-fRDH5) was subretinally injected into 12 RDH5−/− cats. To assess expression and the impact of treatment on retinal function and structure, immunohistochemistry, high-performance liquid chromatography, rod and cone electroretinograms, spectral-domain optical coherence tomography, and semi-thin resin-embedded sectioning were performed.
Results: The expression of the RDH5 transgene improved rod and cone photoreceptor functional recovery following light exposure and shows promise in slowing/halting area centralis (analogous to the human macula) degeneration.
Conclusions: This gene augmentation therapy is a promising approach for the treatment of RDH5-associated retinopathies.
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BibTeX
@article{ford2026gene,
title = {{AAV Gene Augmentation Therapy Rescues the Phenotype in the RDH5−/− Cat Model of Fundus Albipunctatus}},
author = {Laura M. Ford and Kelian Sun and Laurence M. Occelli and Mary E. Enfield and Anahita Daruwalla and Ryan F. Boyd and Philip D. Kiser and Simon M. Petersen-Jones},
journal = {Investigative Ophthalmology \& Visual Science},
year = {2026},
month = oct,
doi = {10.1167/iovs.67.12.45},
url = {https://doi.org/10.1167/iovs.67.12.45},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - AAV Gene Augmentation Therapy Rescues the Phenotype in the RDH5−/− Cat Model of Fundus Albipunctatus
AU - Laura M. Ford
AU - Kelian Sun
AU - Laurence M. Occelli
AU - Mary E. Enfield
AU - Anahita Daruwalla
AU - Ryan F. Boyd
AU - Philip D. Kiser
AU - Simon M. Petersen-Jones
PY - 2026
DA - 2026/10/21
JO - Investigative Ophthalmology & Visual Science
DO - 10.1167/iovs.67.12.45
UR - https://doi.org/10.1167/iovs.67.12.45
AB - Purpose: Retinol dehydrogenase 5 (RDH5) catalyzes the final oxidation for visual pigment regeneration of 11-cis-retinal as part of the visual cycle in the retinal pigment epithelium (RPE). In humans, RDH5 mutations cause fundus albipunctatus characterized by night blindness, accumulation of white-yellowish fundus spots, and, in a subset of patients, macular degeneration. Currently, there is an unmet need for therapies for patients with RDH5 mutations. Using a large-animal cat model of RDH5-associated disease (RDH5−/−), this study aimed to meet these needs through development of a gene augmentation therapy able to rescue RDH5-associated retinopathies. Methods: An adeno-associated virus serotype 2 with triple capsid mutations vector packaged with feline RDH5 cDNA (AAV-VMD2-fRDH5) was subretinally injected into 12 RDH5−/− cats. To assess expression and the impact of treatment on retinal function and structure, immunohistochemistry, high-performance liquid chromatography, rod and cone electroretinograms, spectral-domain optical coherence tomography, and semi-thin resin-embedded sectioning were performed. Results: The expression of the RDH5 transgene improved rod and cone photoreceptor functional recovery following light exposure and shows promise in slowing/halting area centralis (analogous to the human macula) degeneration. Conclusions: This gene augmentation therapy is a promising approach for the treatment of RDH5-associated retinopathies.
SN - 0146-0404
SN - 1552-5783
ER -