ArticlePloS one2014
Natural history of cone disease in the murine model of Leber congenital amaurosis due to CEP290 mutation: determining the timing and expectation of therapy.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Recovery of cone-mediated vision in Lebercilin associated retinal ciliopathy after gene therapy: One-year results of a phase I/II trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Trial
- Gene Editing forThe New England journal of medicine · 2024Trial
- Gene therapy rescues cone function inMolecular therapy. Advances · 2026Article
- Gene therapy rescues cone function in an all-cone retina mouse model with the most common cone opsin C203R missense mutation.PloS one · 2026Article
- The Role of Visual Electrophysiology in Systemic Hereditary Syndromes.International journal of molecular sciences · 2025Review
- Gene editing and its applications in biomedicine.Science China. Life sciences · 2022Review
- The Next Generation of Molecular and Cellular Therapeutics for Inherited Retinal Disease.International journal of molecular sciences · 2021Review
- Spectrum of Disease Severity in Nonsyndromic Patients With Mutations in the CEP290 Gene: A Multicentric Longitudinal Study.Investigative ophthalmology & visual science · 2021Article
- Bardet-Biedl syndrome-7 (Ophthalmic genetics · 2021Article
- Metabolic and Redox Signaling of the Nucleoredoxin-Like-1 Gene for the Treatment of Genetic Retinal Diseases.International journal of molecular sciences · 2020Review
- Insights into photoreceptor ciliogenesis revealed by animal models.Progress in retinal and eye research · 2019Review
- Treatment Potential for Macular Cone Vision in Leber Congenital Amaurosis Due to CEP290 or NPHP5 Mutations: Predictions From Artificial Intelligence.Investigative ophthalmology & visual science · 2019Article
- Leber Congenital Amaurosis (LCA): Potential for Improvement of Vision.Investigative ophthalmology & visual science · 2019Article
- Development of a gene-editing approach to restore vision loss in Leber congenital amaurosis type 10.Nature medicine · 2019Article
- A CEP290 C-Terminal Domain Complements the Mutant CEP290 of Rd16 Mice In Trans and Rescues Retinal Degeneration.Cell reports · 2018Article
- Pupillary Light Reflexes in Severe Photoreceptor Blindness Isolate the Melanopic Component of Intrinsically Photosensitive Retinal Ganglion Cells.Investigative ophthalmology & visual science · 2017Article
- CRISPR/Cas9-Mediated Genome Editing as a Therapeutic Approach for Leber Congenital Amaurosis 10.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- Retinal Structure and Gene Therapy Outcome in Retinoschisin-Deficient Mice Assessed by Spectral-Domain Optical Coherence Tomography.Investigative ophthalmology & visual science · 2016Article
- In vitro and in vivo rescue of aberrant splicing in CEP290-associated LCA by antisense oligonucleotide delivery.Human molecular genetics · 2016Article
- Identification and Correction of Mechanisms Underlying Inherited Blindness in Human iPSC-Derived Optic Cups.Cell stem cell · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundMutations in the CEP290 (cilia-centrosomal protein 290 kDa) gene in Leber congenital amaurosis (LCA) cause early onset visual loss but retained cone photoreceptors in the fovea, which is the potential therapeutic target. A cone-only mouse model carrying a Cep290 gene mutation, rd16;Nrl-/-, was engineered to mimic the human disease. In the current study, we determined the natural history of retinal structure and function in this murine model to permit design of pre-clinical proof-of-concept studies and allow progress to be made toward human therapy. Analyses of retinal structure and visual function in CEP290-LCA patients were also performed for comparison with the results in the model.
methodsRd16;Nrl-/- mice were studied in the first 90 days of life with optical coherence tomography (OCT), electroretinography (ERG), retinal histopathology and immunocytochemistry. Structure and function data from a cohort of patients with CEP290-LCA (n = 15; ages 7-48) were compared with those of the model.
resultsCEP290-LCA patients retain a central island of photoreceptors with normal thickness at the fovea (despite severe visual loss); the extent of this island declined slowly with age. The rd16;Nrl-/- model also showed a relatively slow photoreceptor layer decline in thickness with ∼80% remaining at 3 months. The number of pseudorosettes also became reduced. By comparison to single mutant Nrl-/- mice, UV- and M-cone ERGs of rd16;Nrl-/- were at least 1 log unit reduced at 1 month of age and declined further over the 3 months of monitoring. Expression of GNAT2 and S-opsin also decreased with age.
conclusionsThe natural history of early loss of photoreceptor function with retained cone cell nuclei is common to both CEP290-LCA patients and the rd16;Nrl-/- murine model. Pre-clinical proof-of-concept studies for uniocular therapies would seem most appropriate to begin with intervention at P35-40 and re-study after one month by assaying interocular difference in the UV-cone ERG.
Indexed as
Identifiers
What OpenQuestion holds
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.