Journal article
Increased H3K27 trimethylation contributes to cone survival in a mouse model of cone dystrophy
Cellular and Molecular Life Sciences, Vol.79(8), Art. 409
2022
Abstract
Inherited retinal diseases (IRDs) are a heterogeneous group of blinding disorders, which result in dysfunction or death of the light-sensing cone and rod photoreceptors. Despite individual IRDs (Inherited retinal disease) being rare, collectively, they affect up to 1:2000 people worldwide, causing a significant socioeconomic burden, especially when cone-mediated central vision is affected. This study uses the Pde6ccpfl1 mouse model of achromatopsia, a cone-specific vision loss IRD (Inherited retinal disease), to investigate the potential gene-independent therapeutic benefits of a histone demethylase inhibitor GSK-J4 on cone cell survival. We investigated the effects of GSK-J4 treatment on cone cell survival in vivo and ex vivo and changes in cone-specific gene expression via single-cell RNA sequencing. A single intravitreal GSK-J4 injection led to transcriptional changes in pathways involved in mitochondrial dysfunction, endoplasmic reticulum stress, among other key epigenetic pathways, highlighting the complex interplay between methylation and acetylation in healthy and diseased cones. Furthermore, continuous administration of GSK-J4 in retinal explants increased cone survival. Our results suggest that IRD (Inherited retinal disease)-affected cones respond positively to epigenetic modulation of histones, indicating the potential of this approach in developing a broad class of novel therapies to slow cone degeneration.
Details
- Title
- Increased H3K27 trimethylation contributes to cone survival in a mouse model of cone dystrophy
- Authors/Creators
- A.L. Miller (Author/Creator) - Lions Eye InstituteP.I. Fuller-Carter (Author/Creator) - Lions Eye InstituteK. Masarini (Author/Creator) - University of TübingenM. Samardzija (Author/Creator) - University of ZurichK.W. Carter (Author/Creator) - Analytical Computing Solutions, Willetton, WA, 6155, Australia.R. Rashwan (Author/Creator) - Lions Eye InstituteX.R. Lim (Author/Creator) - Lions Eye InstituteA.A. Brunet (Author/Creator) - Lions Eye InstituteA. Chopra (Author/Creator) - Murdoch UniversityR. Ram (Author/Creator) - Murdoch UniversityC. Grimm (Author/Creator) - University of ZurichM. Ueffing (Author/Creator) - University of TübingenL.S. Carvalho (Author/Creator) - Lions Eye InstituteD. Trifunović (Author/Creator) - University of Tübingen
- Publication Details
- Cellular and Molecular Life Sciences, Vol.79(8), Art. 409
- Publisher
- Birkhauser Verlag Basel
- Identifiers
- 991005540103107891
- Copyright
- © 2022 The Authors.
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.36 Ophthalmology
- 1.36.212 Genetic Retinopathies
- Web Of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- ESI research areas
- Molecular Biology & Genetics