ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Pharmacological Modulation of Photoreceptor Outer Segment Degradation in a Human iPS Cell Model of Inherited Macular Degeneration.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed.
- Review of the clinical electrooculogram - Part 2: the bestrophinopathies and modified protocols.Documenta ophthalmologica. Advances in ophthalmology · 2026Review
- Canine Best disease as a translational model.Eye (London, England) · 2025Review
- Ion channels research in hPSC-RPE cells: bridging benchwork to clinical applications.Journal of translational medicine · 2024Review
- Machine learning-based 3D segmentation of mitochondria in polarized epithelial cells.Mitochondrion · 2024Article
- Multimodal imaging in Best Vitelliform Macular Dystrophy: Literature review and novel insights.European journal of ophthalmology · 2024Review
- Modeling inherited retinal diseases using human induced pluripotent stem cell derived photoreceptor cells and retinal pigment epithelial cells.Frontiers in medicine · 2024Review
- Fixation Location and Stability in Best Vitelliform Macular Dystrophy.Ophthalmology science · 2023Article
- Autophagy in the retinal pigment epithelium: a new vision and future challenges.The FEBS journal · 2022Review
- Human pluripotent stem cells for the modelling of retinal pigment epithelium homeostasis and disease: A review.Clinical & experimental ophthalmology · 2022Review
- Novel mutations in theInternational journal of ophthalmology · 2022Article
- Structure and Function of the Bestrophin family of calcium-activated chloride channels.Channels (Austin, Tex.) · 2021Review
- Extracellular vesicles released by human retinal pigment epithelium mediate increased polarised secretion of drusen proteins in response to AMD stressors.Journal of extracellular vesicles · 2021Article
- Differential Expression of Inflammasome-Related Genes in Induced Pluripotent Stem-Cell-Derived Retinal Pigment Epithelial Cells with or without History of Age-Related Macular Degeneration.International journal of molecular sciences · 2021Article
- Pluripotent Stem Cell-Based Organoid Technologies for Developing Next-Generation Vision Restoration Therapies of Blindness.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2021Review
- A human model of Batten disease shows role of CLN3 in phagocytosis at the photoreceptor-RPE interface.Communications biology · 2021Article
- Knockdown of Claudin-19 in the Retinal Pigment Epithelium Is Accompanied by Slowed Phagocytosis and Increased Expression of SQSTM1.Investigative ophthalmology & visual science · 2021Article
- Role of In Vitro Models for Development of Ophthalmic Delivery Systems.Critical reviews in therapeutic drug carrier systems · 2021Review
- Human iPSC Modeling Reveals Mutation-Specific Responses to Gene Therapy in a Genotypically Diverse Dominant Maculopathy.American journal of human genetics · 2020Article
- Mutation-Dependent Pathomechanisms Determine the Phenotype in the Bestrophinopathies.International journal of molecular sciences · 2020Article
- Selective Histone Deacetylase 6 Inhibitors Restore Cone Photoreceptor Vision or Outer Segment Morphology in Zebrafish and Mouse Models of Retinal Blindness.Frontiers in cell and developmental biology · 2020Article
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Authors and funding
11 authors.
Funding
Abstract
Degradation of photoreceptor outer segments (POS) by retinal pigment epithelium (RPE) is essential for vision, and studies have implicated altered POS processing in the pathogenesis of some retinal degenerative diseases. Consistent with this concept, a recently established hiPSC-RPE model of inherited macular degeneration, Best disease (BD), displayed reduced rates of POS breakdown. Herein we utilized this model to determine (i) if disturbances in protein degradation pathways are associated with delayed POS digestion and (ii) whether such defect(s) can be pharmacologically targeted. We found that BD hiPSC-RPE cultures possessed increased protein oxidation, decreased free-ubiquitin levels, and altered rates of exosome secretion, consistent with altered POS processing. Application of valproic acid (VPA) with or without rapamycin increased rates of POS degradation in our model, whereas application of bafilomycin-A1 decreased such rates. Importantly, the negative effect of bafilomycin-A1 could be fully reversed by VPA. The utility of hiPSC-RPE for VPA testing was further evident following examination of its efficacy and metabolism in a complementary canine disease model. Our findings suggest that disturbances in protein degradation pathways contribute to the POS processing defect observed in BD hiPSC-RPE, which can be manipulated pharmacologically. These results have therapeutic implications for BD and perhaps other maculopathies.
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