ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
Loss of Otx2 in the adult retina disrupts retinal pigment epithelium function, causing photoreceptor degeneration.
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. An erratum has been issued. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 77 citations in OpenAlex.
- A robust cis-regulatory network ensures Otx2 expression during retinal development.Development (Cambridge, England) · 2026Article
- Article
- Single-cell transcriptomics reveals the molecular basis of human iPS cell differentiation into ectodermal ocular lineages.Communications biology · 2024Article
- IGF2BP2 Maintains Retinal Pigment Epithelium Homeostasis by Stabilizing PAX6 and OTX2.Investigative ophthalmology & visual science · 2024Article
- MiR-497-5p ameliorates the oxyhemoglobin-induced subarachnoid hemorrhage injury in vitro by targeting orthodenticle homeobox protein 1 (Otx1) to activate the Nrf2/HO-1 pathway.Molecular genetics and genomics : MGG · 2024Article
- Benefits and Caveats in the Use of Retinal Pigment Epithelium-Specific Cre Mice.International journal of molecular sciences · 2024Review
- SWI/SNF complexes are required for retinal pigmented epithelium differentiation and for the inhibition of cell proliferation and neural differentiation programs.Development (Cambridge, England) · 2023Article
- Chromatin Remodeling Enzyme Snf2h Is Essential for Retinal Cell Proliferation and Photoreceptor Maintenance.Cells · 2023Article
- The LHX2-OTX2 transcriptional regulatory module controls retinal pigmented epithelium differentiation and underlies genetic risk for age-related macular degeneration.PLoS biology · 2023Article
- Disease-causing mutations in genes encoding transcription factors critical for photoreceptor development.Frontiers in molecular neuroscience · 2023Review
- Cell fate decisions, transcription factors and signaling during early retinal development.Progress in retinal and eye research · 2022Review
- Mutations inScience advances · 2022Article
- Functional analysis of the Vsx2 super-enhancer uncovers distinct cis-regulatory circuits controlling Vsx2 expression during retinogenesis.Development (Cambridge, England) · 2022Article
- A Stage-Specific OTX2 Regulatory Network and Maturation-Associated Gene Programs Are Inherent Barriers to RPE Neural Competency.Frontiers in cell and developmental biology · 2022Article
- New Retinal Pigment Epithelial Cell Model to Unravel Neuroprotection Sensors of Neurodegeneration in Retinal Disease.Frontiers in neuroscience · 2022Article
- Fine Tuning of an Oxidative Stress Model with Sodium Iodate Revealed Protective Effect of NF-κB Inhibition and Sex-Specific Difference in Susceptibility of the Retinal Pigment Epithelium.Antioxidants (Basel, Switzerland) · 2021Article
- OTX2 signaling in retinal dysfunction, degeneration and regeneration.Neural regeneration research · 2021Article
- Immunological Aspects of Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2021Article
- Article
- Cell type- and stage-specific expression of Otx2 is regulated by multiple transcription factors andDevelopment (Cambridge, England) · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Photoreceptors are specialized neurons of the retina that receive nursing from the adjacent retinal pigment epithelium (RPE). Frequent in the elderly, photoreceptor loss can originate from primary dysfunction of either cell type. Despite intense interest in the etiology of these diseases, early molecular actors of late-onset photoreceptor degeneration remain elusive, mostly because of the lack of dedicated models. Conditional Otx2 ablation in the adult mouse retina elicits photoreceptor degeneration, providing a new model of late-onset neuronal disease. Here, we use this model to identify the earliest events after Otx2 ablation. Electroretinography and gene expression analyses suggest a nonautonomous, RPE-dependent origin for photoreceptor degeneration. This is confirmed by RPE-specific ablation of Otx2, which results in similar photoreceptor degeneration. In contrast, constitutive Otx2 expression in RPE cells prevents degeneration of photoreceptors in Otx2-ablated retinas. We use chromatin immunoprecipitation followed by massive sequencing (ChIP-seq) analysis to identify the molecular network controlled in vivo by Otx2 in RPE cells. We uncover four RPE-specific functions coordinated by Otx2 that underpin the cognate photoreceptor degeneration. Many direct Otx2 target genes are associated with human retinopathies, emphasizing the significance of the model. Importantly, we report a secondary genetic response after Otx2 ablation, which largely precedes apoptosis of photoreceptors, involving inflammation and stress genes. These findings thus provide novel general markers for clinical detection and prevention of neuronal cell death.
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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.