ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Cone phosphodiesterase-6α' restores rod function and confers distinct physiological properties in the rod phosphodiesterase-6β-deficient rd10 mouse.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
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- Article
- AAV-mediated base-editing therapy ameliorates the disease phenotypes in a mouse model of retinitis pigmentosa.Nature communications · 2023Article
- Dark-reared rd10 mice experience rapid photoreceptor degeneration with short exposure to room-light during in vivo retinal imaging.Experimental eye research · 2022Article
- Sensory Transduction in Photoreceptors and Olfactory Sensory Neurons: Common Features and Distinct Characteristics.Frontiers in cellular neuroscience · 2021Review
- A kinetic analysis of mouse rod and cone photoreceptor responses.The Journal of physiology · 2020Article
- Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.Nature reviews. Drug discovery · 2019Review
- The PDE6 mutation in the rd10 retinal degeneration mouse model causes protein mislocalization and instability and promotes cell death through increased ion influx.The Journal of biological chemistry · 2018Article
- Cone Phosphodiesterase-6γ' Subunit Augments Cone PDE6 Holoenzyme Assembly and Stability in a Mouse Model Lacking Both Rod and Cone PDE6 Catalytic Subunits.Frontiers in molecular neuroscience · 2018Article
- The evolution of rod photoreceptors.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2017Review
- Why are rods more sensitive than cones?The Journal of physiology · 2016Review
- Exchange of Cone for Rod Phosphodiesterase 6 Catalytic Subunits in Rod Photoreceptors Mimics in Part Features of Light Adaptation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Targeted ablation of the Pde6h gene in mice reveals cross-species differences in cone and rod phototransduction protein isoform inventory.The Journal of biological chemistry · 2015Article
- Activation and quenching of the phototransduction cascade in retinal cones as inferred from electrophysiology and mathematical modeling.Molecular vision · 2015Article
- Molecular architecture of photoreceptor phosphodiesterase elucidated by chemical cross-linking and integrative modeling.Journal of molecular biology · 2014Article
- Functional architecture of the retina: development and disease.Progress in retinal and eye research · 2014Review
- Retinal gene therapy using adeno-associated viral vectors: multiple applications for a small virus.Human gene therapy · 2014Article
- Rip3 knockdown rescues photoreceptor cell death in blind pde6c zebrafish.Cell death and differentiation · 2014Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Phosphodiesterase-6 (PDE6) is the key effector enzyme of the vertebrate phototransduction pathway in rods and cones. Rod PDE6 catalytic core is composed of two distinct subunits, PDE6α and PDE6β, whereas two identical PDE6α' subunits form the cone PDE6 catalytic core. It is not known whether this difference in PDE6 catalytic subunit identity contributes to the functional differences between rods and cones. To address this question, we expressed cone PDE6α' in the photoreceptor cells of the retinal degeneration 10 (rd10) mouse that carries a mutation in rod PDEβ subunit. We show that adeno-associated virus-mediated subretinal delivery of PDE6α' rescues rod electroretinogram responses and preserves retinal structure, indicating that cone PDE6α' can couple effectively to the rod phototransduction pathway. We also show that restoration of light sensitivity in rd10 rods is attributable to assembly of PDE6α' with rod PDE6γ. Single-cell recordings revealed that, surprisingly, rods expressing cone PDE6α' are twofold more sensitive to light than wild-type rods, most likely because of the slower shutoff of their light responses. Unlike in wild-type rods, the response kinetics in PDE6α'-treated rd10 rods accelerated with increasing flash intensity, indicating a possible direct feedback modulation of cone PDE6α' activity. Together, these results demonstrate that cone PDE6α' can functionally substitute for rod PDEαβ in vivo, conferring treated rods with distinct physiological properties.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.