ArticleThe Journal of clinical investigation2011
mTOR-mediated dedifferentiation of the retinal pigment epithelium initiates photoreceptor degeneration in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 225 papers, 2 of them syntheses that pooled it.
What it found
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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.
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
225 citing papers in PubMed, 2 syntheses or guidelines pooled it, 310 citations in OpenAlex.
- Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)Autophagy · 2021Guideline
- Autophagy modulation in animal models of corneal diseases: a systematic review.Molecular and cellular biochemistry · 2020Pooled it
- Intravitreal sirolimus for the treatment of geographic atrophy: results of a phase I/II clinical trial.Investigative ophthalmology & visual science · 2014Trial
- Early proteomic and metabolic signatures of liver and eye in OAT-deficient mice.Experimental eye research · 2026Article
- Supramolecular Nrf2-activating peptide nanotherapeutics enable deep retinal penetration and RPE targeting for dry age-related macular degeneration.Materials today. Bio · 2026Article
- Physiological Hypoxia and Pharmacological HIF Stabilization Induce Distinct but Overlapping Responses in Retinal Pigment Epithelial Cells.Pharmaceuticals (Basel, Switzerland) · 2026Article
- DAPL1 restrains RPE PANoptosis in experimental AMD by inhibiting GRP75-mediated mitochondria-associated endoplasmic reticulum membranes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Selective deletion ofiScience · 2026Article
- Small intracellular vesicles outperform small extracellular vesicles in uptake, drug delivery and retinal neuroprotection.Nature biomedical engineering · 2026Article
- Assessing mitochondrial phenotypes in a cybrid model of dry age-related macular degeneration.Molecular vision · 2026Article
- The intersection of mitochondria, lipids, and ferroptosis: a new avenue for dry age-related macular degeneration.Apoptosis : an international journal on programmed cell death · 2025Review
- Nutrient supplementation mitigates retinal dysfunction in Acox1 knockout mice with impaired peroxisomal fatty acid oxidation.Journal of advanced research · 2025Article
- Metabolic dysfunction promoted by mitochondrial DNA mutation burden drives retinal degeneration.bioRxiv : the preprint server for biology · 2025Article
- Article
- Age-Related Macular Degeneration: Cellular and Molecular Signaling Mechanisms.International journal of molecular sciences · 2025Review
- Intraretinal variation in disease severity in the OatExperimental eye research · 2025Article
- Activated mTOR Signaling in the RPE Drives EMT, Autophagy, and Metabolic Disruption, Resulting in AMD-Like Pathology in Mice.Aging cell · 2025Article
- How crosstalk between mitochondria, lysosomes, and other organelles can prevent or promote dry age-related macular degeneration.Experimental eye research · 2025Review
- The Importance of Differentiated RPE Cultures for studying Cell Biological Processes.Advances in experimental medicine and biology · 2025Review
- Eye on the horizon: The metabolic landscape of the RPE in aging and disease.Progress in retinal and eye research · 2025Review
165 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Retinal pigment epithelial (RPE) cell dysfunction plays a central role in various retinal degenerative diseases, but knowledge is limited regarding the pathways responsible for adult RPE stress responses in vivo. RPE mitochondrial dysfunction has been implicated in the pathogenesis of several forms of retinal degeneration. Here we have shown that postnatal ablation of RPE mitochondrial oxidative phosphorylation in mice triggers gradual epithelium dedifferentiation, typified by reduction of RPE-characteristic proteins and cellular hypertrophy. The electrical response of the retina to light decreased and photoreceptors eventually degenerated. Abnormal RPE cell behavior was associated with increased glycolysis and activation of, and dependence upon, the hepatocyte growth factor/met proto-oncogene pathway. RPE dedifferentiation and hypertrophy arose through stimulation of the AKT/mammalian target of rapamycin (AKT/mTOR) pathway. Administration of an oxidant to wild-type mice also caused RPE dedifferentiation and mTOR activation. Importantly, treatment with the mTOR inhibitor rapamycin blunted key aspects of dedifferentiation and preserved photoreceptor function for both insults. These results reveal an in vivo response of the mature RPE to diverse stressors that prolongs RPE cell survival at the expense of epithelial attributes and photoreceptor function. Our findings provide a rationale for mTOR pathway inhibition as a therapeutic strategy for retinal degenerative diseases involving RPE stress.
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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.