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KMID : 0578320210440080613
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Molecules and Cells
2021 Volume.44 No. 8 p.613 ~ p.622
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Retinoid Metabolism in the Degeneration of Pten-Deficient Mouse Retinal Pigment Epithelium
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Kim You-Joung
Park Soo-Yeon
Ha Tae-Jeong
Kim Seung-Beom
Lim So-Yeon
You Han
Kim Jin-Woo
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Abstract
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In vertebrate eyes, the retinal pigment epithelium (RPE) provides structural and functional homeostasis to the retina. The RPE takes up retinol (ROL) to be dehydrogenated and isomerized to 11-cis-retinaldehyde (11-cis-RAL), which is a functional photopigment in mammalian photoreceptors. As excessive ROL is toxic, the RPE must also establish mechanisms to protect against ROL toxicity. Here, we found that the levels of retinol dehydrogenases (RDHs) are commonly decreased in phosphatase tensin homolog (Pten)-deficient mouse RPE, which degenerates due to elevated ROL and that can be rescued by feeding a ROL-free diet. We also identified that RDH gene expression is regulated by forkhead box O (FOXO) transcription factors, which are inactivated by hyperactive Akt in the Pten-deficient mouse RPE. Together, our findings suggest that a homeostatic pathway comprising PTEN, FOXO, and RDH can protect the RPE from ROL toxicity.
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KEYWORD
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forkhead box O, phosphatase tensin homolog, phosphoinositide 3-kinase-Akt pathway, retinal pigment epithelium, retinoids
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