ArticleCell death & disease2018
Translational attenuation and retinal degeneration in mice with an active integrated stress response.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Ubap1l Knockout Mice Model Recapitulates Retinal Degeneration Phenotype Observed in Patients and Exhibits Irregular Photoreceptor Morphology.Investigative ophthalmology & visual science · 2025Article
- Effect of Dync1h1 on Phototransduction Protein Transport and the Development and Maintenance of Photoreceptor Cells in Zebrafish.Investigative ophthalmology & visual science · 2025Article
- Development of TRIB3-Based Therapy as a Gene-Independent Approach to Treat Retinal Degenerative Disorders.International journal of molecular sciences · 2024Article
- 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
- Molecular mechanisms underlying inherited photoreceptor degeneration as targets for therapeutic intervention.Frontiers in cellular neuroscience · 2024Review
- Methods for In Vivo Characterization of Proteostasis in the Mouse Retina.Advances in experimental medicine and biology · 2023Article
- GADD34 Ablation Exacerbates Retinal Degeneration in P23H RHO Mice.International journal of molecular sciences · 2022Article
- Circadian rhythm disruption results in visual dysfunction.FASEB bioAdvances · 2022Article
- mTORC1 regulates high levels of protein synthesis in retinal ganglion cells of adult mice.The Journal of biological chemistry · 2022Article
- Tsc2 knockout counteracts ubiquitin-proteasome system insufficiency and delays photoreceptor loss in retinitis pigmentosa.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Widespread translational control regulates retinal development in mouse.Nucleic acids research · 2021Article
- Tribbles homolog 3-mediated targeting the AKT/mTOR axis in mice with retinal degeneration.Cell death & disease · 2021Article
- Endoplasmic reticulum stress: New insights into the pathogenesis and treatment of retinal degenerative diseases.Progress in retinal and eye research · 2020Review
- Role of Translational Attenuation in Inherited Retinal Degeneration.Investigative ophthalmology & visual science · 2019Article
- Delineating the role of eIF2α in retinal degeneration.Cell death & disease · 2019Article
- Endoplasmic reticulum stress and liver diseases.Liver research (Beijing, China) · 2019Article
- Lutein and Zeaxanthin Isomers Reduce Photoreceptor Degeneration in theBioMed research international · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
An integrated stress response (ISR), identified in several different animal models of inherited retinal degeneration (IRD), is activated following various cellular stresses. The ISR results in the phosphorylation of eIF2α (p-eIF2α) and a consequent halt in protein synthesis. Although generally protective, persistent elevations in p-eIF2α could lead to cell demise. Therefore, we aimed to determine whether ISR activation is associated with diminished translation rates in mice with IRD. Retinal protein extracts from rd16 mice at different time points were analyzed and the retinal levels of protein synthesis were assessed using the SUnSET method. We found that rd16 mice experience persistent ISR activation: p-eIF2α, ATF4, and CHOP were significantly upregulated at P15 and P20. In agreement with ISR activation, we found that rd16 mice experience translational attenuation at P15. Similar to rd16, other IRD models, T17M RHO, and rd10 also demonstrated a decline in protein synthesis, correlating with p-eIF2α elevation. We then assessed the role of PERK and eIF2α in translational attenuation in rd16 using a PERK inhibitor, GSK2606414. We found that while the treatment significantly reduced p-eIF2α, it did not cause a complete recovery in translation. This suggests that eIF2α is not the only or even the primary point of translational control in IRD, and a second node of translational regulation comprising AKT and mTOR should be evaluated. Surprisingly, we found that AKT-mTOR signaling was diminished in rd16 and rd10 retinas, suggesting a potential link between AKT-mTOR and translational inhibition. Therefore, for the first time, this study shows translation attenuation in IRD models, and highlights the potential roles of eIF2α kinases and AKT-mTOR signaling that could grant valuable insight into the potential treatments for IRD.
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