ArticleThe Journal of biological chemistry2015
Di-retinoid-pyridinium-ethanolamine (A2E) Accumulation and the Maintenance of the Visual Cycle Are Independent of Atg7-mediated Autophagy in the Retinal Pigmented Epithelium.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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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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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- The role of autophagy in ocular health: mechanisms, pathologies, and therapeutic strategies.Biology direct · 2026Pooled it
- Exploiting autophagy and related pathways: pioneering new horizons in cataract therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- PHOSPHO1 Suppresses Ferroptosis in Retinal Pigment Epithelial Cells by Reducing the Levels of Phosphatidylethanolamine Molecular Species.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Myelinosome organelles in pathological retinas: ubiquitous presence and dual role in ocular proteostasis maintenance.Neural regeneration research · 2023Review
- Article
- AUTOPHAGY IN THE EYE: FROM PHYSIOLOGY TO PATHOPHYSOLOGY.Autophagy reports · 2023Article
- Autophagy in the retinal pigment epithelium: a new vision and future challenges.The FEBS journal · 2022Review
- The effect of A2E on lysosome membrane permeability during blue light-induced human RPEs apoptosis.BMC ophthalmology · 2022Article
- Complement activation, lipid metabolism, and mitochondrial injury: Converging pathways in age-related macular degeneration.Redox biology · 2020Review
- The cell biology of the retinal pigment epithelium.Progress in retinal and eye research · 2020Review
- Clinical Course and Electron Microscopic Findings in Lymphocytes of Patients withInternational journal of molecular sciences · 2020Article
- Autophagy in Age-Related Macular Degeneration: A Regulatory Mechanism of Oxidative Stress.Oxidative medicine and cellular longevity · 2020Review
- Autophagy resists EMT process to maintain retinal pigment epithelium homeostasis.International journal of biological sciences · 2019Article
- Autophagy and Age-Related Eye Diseases.BioMed research international · 2019Review
- Autophagy Dysfunction, Cellular Senescence, and Abnormal Immune-Inflammatory Responses in AMD: From Mechanisms to Therapeutic Potential.Oxidative medicine and cellular longevity · 2019Review
- Lipocalin 2 Plays an Important Role in Regulating Inflammation in Retinal Degeneration.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- A2E-associated cell death and inflammation in retinal pigmented epithelial cells from human induced pluripotent stem cells.Stem cell research · 2018Article
- Adaptations in rod outer segment disc membranes in response to environmental lighting conditions.Biochimica et biophysica acta. Molecular cell research · 2017Article
- Absence of DJ-1 causes age-related retinal abnormalities in association with increased oxidative stress.Free radical biology & medicine · 2017Article
- Early AMD-like defects in the RPE and retinal degeneration in aged mice with RPE-specific deletion ofMolecular vision · 2017Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Autophagy is an evolutionarily conserved catabolic mechanism that relieves cellular stress by removing/recycling damaged organelles and debris through the action of lysosomes. Compromised autophagy has been implicated in many neurodegenerative diseases, including retinal degeneration. Here we examined retinal phenotypes resulting from RPE-specific deletion of the autophagy regulatory gene Atg7 by generating Atg7(flox/flox);VMD2-rtTA-cre+ mice to determine whether autophagy is essential for RPE functions including retinoid recycling. Atg7-deficient RPE displayed abnormal morphology with increased RPE thickness, cellular debris and vacuole formation indicating that autophagy is important in maintaining RPE homeostasis. In contrast, 11-cis-retinal content, ERGs and retinal histology were normal in mice with Atg7-deficient RPE in both fasted and fed states. Because A2E accumulation in the RPE is associated with pathogenesis of both Stargardt disease and age-related macular degeneration (AMD) in humans, deletion of Abca4 was introduced into Atg7(flox/flox);VMD2-rtTA-cre+ mice to investigate the role of autophagy during A2E accumulation. Comparable A2E concentrations were detected in the eyes of 6-month-old mice with and without Atg7 from both Abca4(-/-) and Abca4(+/+) backgrounds. To identify other autophagy-related molecules involved in A2E accumulation, we performed gene expression array analysis on A2E-treated human RPE cells and found up-regulation of four autophagy related genes; DRAM1, NPC1, CASP3, and EIF2AK3/PERK. These observations indicate that Atg7-mediated autophagy is dispensable for retinoid recycling and A2E deposition; however, autophagy plays a role in coping with stress caused by A2E accumulation.
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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.