Gene augmentation therapy to rescue degenerative photoreceptors in a Cwc27 mutant mouse model.

TitleGene augmentation therapy to rescue degenerative photoreceptors in a Cwc27 mutant mouse model.
Publication TypeJournal Article
Year of Publication2023
AuthorsLu, J, Zheng, KQ, Bertrand, RElaine, Quinlan, J, Ferdous, S, Srinivasan, T, Oh, S, Wang, K, Chen, R
JournalExp Eye Res
Date Published2023 Sep
KeywordsAnimals, Disease Models, Animal, Electroretinography, Genetic Therapy, Genetic Vectors, Mice, Retina, Retinal Cone Photoreceptor Cells, Retinal Degeneration

Previous reports have demonstrated that defects in the spliceosome-associated protein CWC27 can lead to the degeneration of retinal cells in Cwc27 mutant mouse models. However, it is unknown whether gene replacement therapy can rescue this phenotype. The purpose of this study was to evaluate whether AAV based gene therapy could rescue the retinal degeneration observed in Cwc27 mutant mice. By 6 months of age, Cwc27 mutant mice show a retinal degenerative phenotype, including morphological and functional abnormalities, primarily driven by the death of photoreceptors. We hypothesize that subretinal injection of AAV8 to drive exogenous CWC27 protein expression will improve the retinal phenotype. We evaluated these improvements after gene therapy with electroretinography (ERG) and histology, either hematoxylin and eosin (H&E) or immunostaining. In this study, we demonstrated that subretinal injection of AAV8-GRK-Cwc27-FLAG in mutant mice can improve the functionality and morphology of the retina. Immunostaining analyses revealed a notable decrease in photoreceptor degeneration, including cone cell degeneration, in the AAV-injected eyes compared to the PBS-injected eyes. Based on these results, gene replacement therapy could be a promising method for treating retinal degeneration caused by mutations in Cwc27.

Alternate JournalExp Eye Res
PubMed ID37479075
Grant ListR01 EY022356 / EY / NEI NIH HHS / United States
R01 EY020540 / EY / NEI NIH HHS / United States

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