Autophagy protects the retina from light-induced degeneration
Open accessAbstract
Autophagy is a conserved feature of lysosome-mediated intracellular degradation. Dysregulated autophagy is implicated as a contributor in neurodegenerative diseases; however, the role of autophagy in retinal degeneration remains largely unknown. Here, we report that the photo-activated visual chromophore, all-trans-retinal, modulated autophagosome formation in ARPE19 retinal cells. Increased formation of autophagosomes in these cells was observed when incubated with 2.5 μM all-trans-retinal, a condition that did not cause cell death after 24 h in culture. However, autophagosome formation was decreased at concentrations, which caused cell death. Increased expression of activating transcription factor 4 (Atf4), which indicates the activation of oxidative stress, was recorded in response to light illumination in retinas of Abca4(-/-)Rdh8(-/-) mice, which showed delayed clearance of all-trans-retinal after light exposure. Expression of autophagosome marker LC3B-II and mitochondria-specific autophagy, mitophagy, regulator Park2, were significantly increased in the retinas of Abca4(-/-)Rdh8(-/-) mice after light exposure, suggesting involvement of autophagy and mitophagy in the pathogenesis of light-induced retinal degeneration. Deletion of essential genes required for autophagy, including Beclin1 systemically or Atg7 in only rod photoreceptors resulted in increased susceptibility to light-induced retinal damage. Increased photoreceptor cell death was observed when retinas lacking the rod photoreceptor-specific Atg7 gene were coincubated with 20 μM all-trans-retinal. Park2(-/-) mice also displayed light-induced retinal degeneration. Ultra-structural analyses showed mitochondrial and endoplasmic reticulum impairment in retinas of these model animals after light exposure. Taken together, these observations provide novel evidence implicating an important role of autophagy and mitophagy in protecting the retina from all-trans-retinal- and light-induced degeneration.
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Autophagy is upregulated in the RPE as an early stress response after exposure to varied insults such as intense light, oxidative stress, mitochondrial poisons, and cigarette smoke.
“Like most other tissues, autophagy is upregulated in the RPE as an early stress response after exposure to varied insults such as intense light, oxidative stress, mitochondrial poisons, and cigarette smoke (Reme et al., 1999; Kunchithapautham and Rohrer, 2007; Chen et al., 2013; Wang et al., 2014).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Chen et al., 2013
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- Authors
- Chen, Y., Sawada, O., Kohno, H., Le, Y.-Z., Subauste, C., Maeda, T., & Maeda, A.
- Affiliations
- Shanghai University of Traditional Chinese Medicine (CN)
- Case Western Reserve University (US)
- University of Oklahoma Health Sciences Center (US)
- Corresponding author
- Maeda, Akiko
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 288
- Issue
- 11
- Pages
- 7506-7518
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3597791
- OpenAlex
- W2052550497
- Cited by
- 152
- References
- 41
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 4 · 2023: 10 · 2022: 12 · 2021: 17 · 2020: 16 · 2019: 13 · 2018: 11 · 2017: 8 · 2016: 11 · 2015: 13 · 2014: 12 · 2013: 7
- FWCI
- 6.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Research to Prevent Blindness
- Ohio Lions Eye Research Foundation
- National Institutes of Health
- Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning
- National Eye Institute (R01EY022658, K08EY019880, K08EY019031, R24EY021126, R01EY018341, P30EY011373)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- autophagy, mitophagy, light-induced retinal degeneration, all-trans-retinal, retinal degeneration, photoreceptor cell death, ATG7, PARK2, ABCA4, LC3B, oxidative stress, ATF4, mitochondrial damage, endoplasmic reticulum damage, Beclin-1, rod photoreceptors
- MeSH terms
- Beclin-1, Autophagy-Related Protein 7, Alcohol Dehydrogenase, Alcohol Oxidoreductases, Animals, Autophagy, Cell Line, Humans, Light, Lysosomes, Membrane Proteins, Mice, Transgenic, Microtubule-Associated Proteins, Photic Stimulation, Retina, Retinal Degeneration, Rhodopsin, Vitamin A, Cell Death, Apoptosis, ATP-Binding Cassette Transporters, Ubiquitin-Activating Enzymes, Ubiquitin-Protein Ligases, Apoptosis Regulatory Proteins, Mice
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