Abstract
218 Efficacy of subretinal gene therapy in moderately advanced retinal degeneration in the Bardet-Biedl syndrome type 10 mouse
Journal of AAPOS, Vol.29(4), 104500
08/2025
DOI: 10.1016/j.jaapos.2025.104500
Abstract
Introduction
Bardet-Biedl syndrome (BBS) is a pleiotropic disease caused by mutations in at least 28 genes. Bardet-Biedl syndrome type 10 (BBS10) causes rapid retinal degeneration. Our lab previously demonstrated photoreceptor rescue in Bbs10−/− mice through subretinal gene augmentation at 1-month-old (∼ 3 years in humans). This study examines efficacy of subretinal gene therapy in Bbs10−/− mice at 3 months old, closer to the typical patient presentation age (∼8-10 years).
Methods
The mouse Bbs10 gene was cloned into a shuttle plasmid containing a CMV promoter and packaged into an AAV2/Anc80 viral vector (L. Vandenberghe). Three-month-old Bbs10-/- mice (n = 13) were subretinally injected with 2 μL of AAV2/Anc80-Bbs10 at either 1.6E9 vg/eye or 8E9 vg/eye. Optical coherence tomography (OCT), electroretinography (ERG), and a visually guided swim assay were utilized to assess efficacy at multiple time points up to one year post-treatment.
Results
Eyes treated at 3 months old had thicker outer nuclear layers on OCT compared to untreated eyes at 3 months post treatment (P = 0.0109, 0.0062). ERG rod b-wave amplitudes were significantly higher in eyes treated with 8E9 vg/eye compared to untreated eyes (P = 0.037). Cone ERG showed no difference between treated and untreated eyes. Treated mice showed a trend toward improved visually guided dark swim times.
Conclusion/Relevance
In Bbs10−/− mice, treatment at 1 month rescued rods and cones, while treatment at 3 months only rescued rods. This suggests that later BBS10 treatment may rescue ambulatory vision, while early treatment is needed for detailed acuity. Early diagnosis will be crucial when gene therapy becomes available.
Details
- Title: Subtitle
- 218 Efficacy of subretinal gene therapy in moderately advanced retinal degeneration in the Bardet-Biedl syndrome type 10 mouse
- Creators
- Brianna LobeckYing HsuSarah StanleyJoseph LairdEmily KalmanekEthan BrandauerArlene Drack
- Resource Type
- Abstract
- Publication Details
- Journal of AAPOS, Vol.29(4), 104500
- DOI
- 10.1016/j.jaapos.2025.104500
- ISSN
- 1091-8531
- Language
- English
- Date published
- 08/2025
- Academic Unit
- Stead Family Department of Pediatrics; Biochemistry and Molecular Biology; Ophthalmology and Visual Sciences
- Record Identifier
- 9984964237002771
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