ArticleAging2021
Pharmacologic activation of autophagy without direct mTOR inhibition as a therapeutic strategy for treating dry macular degeneration.
Article in Aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- Autophagy in Sensorineural Hearing Loss: Jekyll or Hyde?International journal of molecular sciences · 2026Review
- Synergistic Autophagy-Related Mechanisms of Protection Against Brain Aging and AD: Cellular Pathways and Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Targeting Lysosomal Dysfunction and Oxidative Stress in Age-Related Macular Degeneration.Antioxidants (Basel, Switzerland) · 2025Review
- Hallmarks of aging in age-related macular degeneration and age-related neurological disorders: novel insights into common mechanisms and clinical relevance.Eye (London, England) · 2025Review
- The retinal pigment epithelium: Functions and roles in ocular diseases.Fundamental research · 2024Review
- Reassessing retinal pigment epithelial ketogenesis: Enzymatic assays for ketone body levels provide inaccurate results.Experimental eye research · 2024Article
- Article
- Medium Depth Influences O2 Availability and Metabolism in Human RPE Cultures.Investigative ophthalmology & visual science · 2023Article
- Improved Lipofuscin Models and Quantification of Outer Segment Phagocytosis Capacity in Highly Polarized Human Retinal Pigment Epithelial Cultures.Journal of visualized experiments : JoVE · 2023Article
- Precision Medicines for Retinal Lipid Metabolism-Related Pathologies.Journal of personalized medicine · 2023Review
- Article
- Knockout of AMD-associated geneAging · 2023Article
- Autophagy in age-related macular degeneration.Autophagy · 2023Review
- Curcumin as a Perspective Protection for Retinal Pigment Epithelium during Autophagy Inhibition in the Course of Retinal Degeneration.Current neuropharmacology · 2023Article
- Photooxidation of A2E by Blue Light Regulates Heme Oxygenase 1 Expression via NF-κB and Lysine Methyltransferase 2A in ARPE-19 Cells.Life (Basel, Switzerland) · 2022Article
- Activation of autophagy reverses progressive and deleterious protein aggregation in PRPF31 patient-induced pluripotent stem cell-derived retinal pigment epithelium cells.Clinical and translational medicine · 2022Article
- New Retinal Pigment Epithelial Cell Model to Unravel Neuroprotection Sensors of Neurodegeneration in Retinal Disease.Frontiers in neuroscience · 2022Article
- Role of Nuclear Factor of Activated T Cells (NFAT) Pathway in Regulating Autophagy and Inflammation in Retinal Pigment Epithelial Cells.International journal of molecular sciences · 2021Article
- Brown bowel syndrome: a systematic review.Annals of gastroenterologyReview
- Targeting Lipid Metabolism for the Treatment of Age-Related Macular Degeneration: Insights from Preclinical Mouse Models.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and TherapeuticsReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Dry age-related macular degeneration (AMD) is marked by the accumulation of extracellular and intracellular lipid-rich deposits within and around the retinal pigment epithelium (RPE). Inducing autophagy, a conserved, intracellular degradative pathway, is a potential treatment strategy to prevent disease by clearing these deposits. However, mTOR inhibition, the major mechanism for inducing autophagy, disrupts core RPE functions. Here, we screened autophagy inducers that do not directly inhibit mTOR for their potential as an AMD therapeutic in primary human RPE culture. Only two out of more than thirty autophagy inducers tested reliably increased autophagy flux in RPE, emphasizing that autophagy induction mechanistically differs across distinct tissues. In contrast to mTOR inhibitors, these compounds preserved RPE health, and one inducer, the FDA-approved compound flubendazole (FLBZ), reduced the secretion of apolipoprotein that contributes to extracellular deposits termed drusen. Simultaneously, FLBZ increased production of the lipid-degradation product β-hydroxybutyrate, which is used by photoreceptor cells as an energy source. FLBZ also reduced the accumulation of intracellular deposits, termed lipofuscin, and alleviated lipofuscin-induced cellular senescence and tight-junction disruption. FLBZ triggered compaction of lipofuscin-like granules into a potentially less toxic form. Thus, induction of RPE autophagy without direct mTOR inhibition is a promising therapeutic approach for dry AMD.
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What Socratic holds
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 Socratic graph.