Autophagy supports color vision
Open accessAbstract
Cones comprise only a small portion of the photoreceptors in mammalian retinas. However, cones are vital for color vision and visual perception, and their loss severely diminishes the quality of life for patients with retinal degenerative diseases. Cones function in bright light and have higher demand for energy than rods; yet, the mechanisms that support the energy requirements of cones are poorly understood. One such pathway that potentially could sustain cones under basal and stress conditions is macroautophagy. We addressed the role of macroautophagy in cones by examining how the genetic block of this pathway affects the structural integrity, survival, and function of these neurons. We found that macroautophagy was not detectable in cones under normal conditions but was readily observed following 24 h of fasting. Consistent with this, starvation induced phosphorylation of AMPK specifically in cones indicating cellular starvation. Inhibiting macroautophagy in cones by deleting the essential macroautophagy gene Atg5 led to reduced cone function following starvation suggesting that cones are sensitive to systemic changes in nutrients and activate macroautophagy to maintain their function. ATG5-deficiency rendered cones susceptible to light-induced damage and caused accumulation of damaged mitochondria in the inner segments, shortening of the outer segments, and degeneration of all cone types, revealing the importance of mitophagy in supporting cone metabolic needs. Our results demonstrate that macroautophagy supports the function and long-term survival of cones providing for their unique metabolic requirements and resistance to stress. Targeting macroautophagy has the potential to preserve cone-mediated vision during retinal degenerative diseases.
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Fasting for 24 h significantly enhanced GFP-LC3 puncta and decreased SQSTM1 in RPE, suggesting fasting induced autophagy in the RPE.
“Under fed conditions, GFP-LC3 was diffuse throughout the cytoplasm (Fig. 4A, Left panel); however, following 24 h of fasting GFP-LC3 puncta were significantly enhanced (Fig. 4A, right panel, arrows) and we simultaneously observed decreased SQSTM1 (Fig. 4B) further suggesting that fasting mice induced autophagy in the RPE.”
From RUBCN/rubicon and EGFR regulate lysosomal degradative processes in the retinal pigment epithelium (RPE) of the eye (2017) · cites this paper as [33]
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Autophagy in major human diseases
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- Authors
- Zhou, Z., Vinberg, F., Schottler, F., Doggett, T. A., Kefalov, V. J., & Ferguson, T. A.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Ferguson, Thomas A
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2015-10-03
- Volume
- 11
- Issue
- 10
- Pages
- 1821-1832
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- PMC
- PMC4824586
- OpenAlex
- W1928243159
- Cited by
- 40
- References
- 62
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 1 · 2023: 3 · 2022: 7 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 2 · 2015: 1
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Figshare (cc-by)
- Funders
- Research to Prevent Blindness (EY02687)
- BrightFocus Foundation
- National Institutes of Health (EY02687)
- National Eye Institute (EY 02687, P30EY002687, R01EY019312, EY 015570, EY019312, R01EY015570)
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Keywords
- macroautophagy, cone photoreceptors, color vision, ATG5, mitophagy, AMPK phosphorylation, starvation, retinal degeneration, mitochondrial damage, photoreceptor survival, retinal energy metabolism
- MeSH terms
- Animals, Autophagy, Color, Light, Mice, Transgenic, Retina, Retinal Degeneration, Starvation, Retinal Rod Photoreceptor Cells, Retinal Cone Photoreceptor Cells, Color Vision
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