Journal
BIOLOGY OPEN
Volume 10, Issue 11, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/bio.058600
Keywords
Vitamin A; Retina; A2E; Age-related macular degeneration; Stargardt disease
Categories
Funding
- U.S. National Institutes of Health, National Eye Institute [1R01EY021207]
- Research to Prevent Blindness (RPB) Inc., NY, USA
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The study found that the vitamin A byproduct A2E alone is sufficient to cause retinal damage and functional decline, potentially being the root cause of retinal diseases. Delaying the formation of vitamin A byproducts could help prevent retinal diseases.
In the most prevalent retinal diseases, including Stargardt disease and age-related macular degeneration (AMD), byproducts of vitamin A form in the retina abnormally during the vitamin A cycle. Despite evidence of their toxicity, whether these vitamin A cycle byproducts contribute to retinal disease, are symptoms, beneficial, or benign has been debated. We delivered a representative vitamin A byproduct, A2E, to the rat's retina and monitored electrophysiological, histological, proteomic, and transcriptomic changes. We show that the vitamin A cycle byproduct is sufficient alone to damage the RPE, photoreceptor inner and outer segments, and the outer plexiform layer, cause the formation of sub-retinal debris, alter transcription and protein synthesis, and diminish retinal function. The presented data are consistent with the theory that the formation of vitamin A byproducts during the vitamin A cycle is neither benign nor beneficial but may be sufficient alone to cause the most prevalent forms of retinal disease. Retarding the formation of vitamin A byproducts could potentially address the root cause of several retinal diseases to eliminate the threat of irreversible blindness for millions of people.
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