ArticlePloS one2016
Limited ATF4 Expression in Degenerating Retinas with Ongoing ER Stress Promotes Photoreceptor Survival in a Mouse Model of Autosomal Dominant Retinitis Pigmentosa.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
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- Anti-TNFα and Anti-IL-1β Monoclonal Antibodies Preserve BV-2 Microglial Homeostasis Under Hypoxia by Mitigating Inflammatory Reactivity and ATF4/MAPK-Mediated Apoptosis.Antioxidants (Basel, Switzerland) · 2025Article
- Effect of Dync1h1 on Phototransduction Protein Transport and the Development and Maintenance of Photoreceptor Cells in Zebrafish.Investigative ophthalmology & visual science · 2025Article
- Mechanisms of Rhodopsin-Related Inherited Retinal Degeneration and Pharmacological Treatment Strategies.Cells · 2025Review
- The Involvement of Unfolded Protein Response in the Mechanism of Nitrogen Mustard-Induced Ocular Toxicity.The Journal of pharmacology and experimental therapeutics · 2024Article
- The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease.Progress in retinal and eye research · 2024Review
- Endoplasmic reticulum stress: molecular mechanism and therapeutic targets.Signal transduction and targeted therapy · 2023Review
- PERK Inhibition Suppresses Neovascularization and Protects Neurons During Ischemia-Induced Retinopathy.Investigative ophthalmology & visual science · 2023Article
- PERK prevents rhodopsin degradation during retinitis pigmentosa by inhibiting IRE1-induced autophagy.The Journal of cell biology · 2023Article
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- Retinal injury mouse model and pathophysiological assessment of the effect of arsenical vesicants.Experimental eye research · 2023Article
- Increased H3K27 trimethylation contributes to cone survival in a mouse model of cone dystrophy.Cellular and molecular life sciences : CMLS · 2022Article
- Inherited Retinal Dystrophies: Role of Oxidative Stress and Inflammation in Their Physiopathology and Therapeutic Implications.Antioxidants (Basel, Switzerland) · 2022Review
- Cellular stress signaling and the unfolded protein response in retinal degeneration: mechanisms and therapeutic implications.Molecular neurodegeneration · 2022Review
- A protein-trap allele reveals roles for Drosophila ATF4 in photoreceptor degeneration, oogenesis and wing development.Disease models & mechanisms · 2022Article
- Targeting Endoplasmic Reticulum Stress as an Effective Treatment for Alcoholic Pancreatitis.Biomedicines · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
T17M rhodopsin expression in rod photoreceptors leads to severe retinal degeneration and is associated with the activation of ER stress related Unfolded Protein Response (UPR) signaling. Here, we show a novel role of a UPR transcription factor, ATF4, in photoreceptor cellular pathology. We demonstrated a pro-death role for ATF4 overexpression during autosomal dominant retinitis pigmentosa (ADRP). Based on our results in ATF4 knockout mice and adeno-associated viral (AAV) delivery of ATF4 to the retina, we validated a novel therapeutic approach targeting ATF4 over the course of retinal degeneration. In T17M rhodopsin retinas, we observed ATF4 overexpression concomitantly with reduction of p62 and elevation of p53 levels. These molecular alterations, together with increased CHOP and caspase-3/7 activity, possibly contributed to the mechanism of photoreceptor cell loss. Conversely, ATF4 knockdown retarded retinal degeneration in 1-month-old T17M Rhodopsin mice and promoted photoreceptor survival, as measured by scotopic and photopic ERGs and photoreceptor nuclei row counts. Similarly, ATF4 knockdown also markedly delayed retinal degeneration in 3-month-old ADRP animals. This delay was accompanied by a dramatic decrease in UPR signaling, the launching of anti-oxidant defense, initiation of autophagy, and improvement of rhodopsin biosynthesis which together perhaps combat the cellular stress associated with T17M rhodopsin. Our data indicate that augmented ATF4 signals during retinal degeneration plays a cytotoxic role by triggering photoreceptor cell death. Future ADRP therapy regulating ATF4 expression can be developed to treat retinal degenerative disorders associated with activated UPR.
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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.