Peroxisome turnover and diurnal modulation of antioxidant activity in retinal pigment epithelia utilizes microtubule-associated protein 1 light chain 3B (LC3B)
Open accessPublished version of a preprint
Abstract
Abstract The retinal pigment epithelium (RPE) supports the outer retina through essential roles in the retinoid the visual cycle, nutrient supply, ion exchange and waste removal. Each day the RPE removes the oldest ∼10% of photoreceptor outer segments through phagocytic uptake, which peaks in a synchronous burst following light onset. Impaired degradation of phagocytosed OS material by the RPE can lead to toxic accumulation of lipids, oxidative tissue damage, inflammation and cell death. OSs are rich in very long chain fatty acids which are preferentially catabolized in peroxisomes. Despite the importance of lipid degradation in RPE function, the regulation of peroxisome number and activity relative to diurnal OS ingestion is relatively unexplored. Using immunohistochemistry, immunoblotting and catalase activity assays, we investigated peroxisome abundance and activity at 6 am, 7 am (at lights on), 8 am, and 3 pm, in WT mice and mice lacking microtubule-associated protein 1 light chain 3B (LC3B), that have impaired degradation of phagosomes. We found that catalase activity, but not protein expression, is 50% higher in the morning compared with 3 pm, in RPE of WT but not LC3B -/- mice. Surprisingly, we found that peroxisome abundance was stable during the day, however numbers are elevated overall in LC3B -/- mice, implicating LC3B in autophagic organelle turnover in RPE. Our data suggest that RPE peroxisome function is regulated in coordination with phagocytosis, possibly through direct enzyme regulation, and may serve to prepare RPE peroxisomes for daily surges in ingested lipid-rich OS.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Despite diurnal peaks in phagocytosis, peroxisome numbers are stable throughout the day in mouse RPE; however, catalase activity is elevated during the early morning hours when ingested phagosomes are highest, suggesting enzyme induction.
“Surprisingly, despite diurnal peaks in phagocytosis and therefore peaks in substrate availability for β-oxidation, peroxisome numbers are stable throughout the day in mouse RPE. However, activity of the peroxisome antioxidant catalase is elevated during the early morning hours when numbers of ingested phagosomes are highest, suggesting enzyme induction (Daniele et al., 2019).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Daniele et al., 2019
Impaired degradation rather than proliferation is suggested by elevated peroxisome numbers in mice lacking expression of LC3B.
“The possibility of impaired degradation rather than proliferation is suggested by a recent finding of elevated peroxisome numbers in mice lacking expression of LC3B (Daniele et al., 2019).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Daniele et al., 2019
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 82 · Cited by 16
- Authors
- Daniele, L. L., Caughey, J., Volland, S., Sharp, R. C., Dhingra, A., Williams, D. S., Philp, N. J., & Boesze-Battaglia, K.
- Affiliations
- University of Pennsylvania (US)
- University of California, Los Angeles (US)
- Thomas Jefferson University (US)
- Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
- ORCID
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2019-12-01
- Volume
- 317
- Issue
- 6
- Pages
- C1194-C1204
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- PMC
- PMC6962520
- OpenAlex
- W2977885645
- Cited by
- 16
- References
- 82
- Citations by year
- 2026: 3 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 2
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ScholarlyCommons (University of Pennsylvania) (submittedVersion)
- Funders
- HHS | NIH | National Eye Institute (EY010420-21, EY026525-02, P30EY000331, R01EY027442)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Keywords
- retinal pigment epithelium, LC3B, autophagy, photoreceptor outer segment phagocytosis, diurnal cycle, antioxidant activity, catalase activity, very long chain fatty acids, lipid degradation
- MeSH terms
- Animals, Autophagy, Catalase, Circadian Rhythm, Fatty Acids, Female, Gene Expression Regulation, Humans, Light, Male, Mice, Inbred C57BL, Microtubule-Associated Proteins, Oxidation-Reduction, Phagocytosis, Mice, Knockout, Peroxisomes, Mice, Retinal Pigment Epithelium, Light Signal Transduction
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
