ArticleNeuroscience letters2015
Unfolded protein response is activated in aged retinas.
Article in Neuroscience letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- The role of autophagy in ocular health: mechanisms, pathologies, and therapeutic strategies.Biology direct · 2026Pooled it
- Targeting of Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) Signaling Pathway in Age-Related Eye Diseases: Molecular Mechanisms and Opportunities for therapy.Journal of biochemical and molecular toxicology · 2026Review
- Age-dependent induction of ER stress in retinal pigment epithelium impairs phagocytosis via ADAM17-dependent MERTK shedding.The Journal of biological chemistry · 2026Article
- Endoplasmic reticulum stress and rhodopsin accumulation in an organoid model of Retinitis Pigmentosa carrying a RHO pathogenic variant.Stem cell research & therapy · 2025Article
- Mitochondria-Associated Membranes in Aging and Senescence.Aging and disease · 2024Review
- Metformin inhibits inflammatory response and endoplasmic reticulum stress to improve hypothalamic aging in obese mice.iScience · 2023Article
- AGAP1-associated endolysosomal trafficking abnormalities link gene-environment interactions in neurodevelopmental disorders.Disease models & mechanisms · 2023Article
- Cellular stress signaling and the unfolded protein response in retinal degeneration: mechanisms and therapeutic implications.Molecular neurodegeneration · 2022Review
- Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy.International journal of molecular sciences · 2021Review
- Aging of the Retina: Molecular and Metabolic Turbulences and Potential Interventions.Annual review of vision science · 2021Review
- 2,3,5,6-Tetramethylpyrazine protects retinal photoreceptors against endoplasmic reticulum stress by modulating ATF4-mediated inhibition of PRP aggregation.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Therapeutic effect of Keap1-Nrf2-ARE pathway-related drugs on age-related eye diseases through anti-oxidative stress.International journal of ophthalmology · 2021Review
- ER stress activates immunosuppressive network: implications for aging and Alzheimer's disease.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Effect of ER stress on sphingolipid levels and apoptotic pathways in retinal pigment epithelial cells.Redox biology · 2020Article
- Rhodopsin: A Potential Biomarker for Neurodegenerative Diseases.Frontiers in neuroscience · 2020Review
- Article
- Protein synthesis and quality control in aging.Aging · 2018Review
- The positive effect of chick embryo and nutrient mixture on bone marrow- derived mesenchymal stem cells from aging rats.Scientific reports · 2018Article
- Kinases of eIF2a Switch Translation of mRNA Subset during Neuronal Plasticity.International journal of molecular sciences · 2017Review
- Endoplasmic reticulum proteostasis impairment in aging.Aging cell · 2017Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
An unfolded protein response (UPR) in addition to oxidative stress and the inflammatory response is known to be activated in age-related ocular disorders, such as macular degeneration, diabetic retinopathy, glaucoma, and cataracts. Therefore, we aimed to investigate whether healthy aged retinas display UPR hallmarks, in order to establish a baseline for the activated UPR markers for age-related ocular diseases. Using western blotting, we determined that the hallmarks of the UPR PERK arm, phosphorylated (p) eIF2a, ATF4, and GADD34, were significantly altered in aged vs. young rat retinas. The cleaved pATF6 (50) and CHOP proteins were dramatically upregulated in the aged rodent retinas, indicating the activation of the ATF6 UPR arm. The UPR activation was associated with a drop in rhodopsin expression and in the NRF2 and HO1 levels, suggesting a decline in the anti-oxidant defense in aged retinas. Moreover, we observed down-regulation of anti-inflammatory IL-10 and IL-13 and upregulation of pro-inflammatory RANTES in the healthy aged retinas, as measured using the Bio-plex assay. Our results suggest that cellular homeostasis in normal aged retinas is compromised, resulting in the concomitant activation of the UPR, oxidative stress, and inflammatory signaling. This knowledge brings us closer to understanding the cellular mechanisms of the age-related retinopathies and ocular disorders characterized by an ongoing UPR, and highlight the UPR signaling molecules that should be validated as potential therapeutic targets.
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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.