Retinoid Metabolism in the Degeneration of Pten-Deficient Mouse Retinal Pigment Epithelium

• Published in: Molecules and cells Vol. 44; no. 8; pp. 613 - 622
• Main Authors: Kim, You-Joung, Park, Sooyeon, Ha, Taejeong, Kim, Seungbeom, Lim, Soyeon, You, Han, Kim, Jin Woo
• Format: Journal Article
• Language: English
• Published: United States Korean Society for Molecular and Cellular Biology 01.08.2021; 한국분자세포생물학회
• Subjects: Alcohol Oxidoreductases - metabolism; Aldehyde Dehydrogenase - metabolism; Animals; Diet; Forkhead Transcription Factors - metabolism; Mice, Transgenic; PTEN Phosphohydrolase - deficiency; PTEN Phosphohydrolase - metabolism; Retinal Degeneration - metabolism; Retinal Degeneration - pathology; Retinal Pigment Epithelium - metabolism; Retinal Pigment Epithelium - pathology; Retinoids - metabolism; Vitamin A - metabolism; 생물학; phosphoinositide 3-kinase-Akt pathway; phosphatase tensin homolog; retinal pigment epithelium; retinoids; forkhead box O
• ISSN: 1016-8478; 0219-1032
• DOI: 10.14348/molcells.2021.0138

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- -retinaldehyde (11- -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 ( )-deficient mouse RPE, which degenerates due to elevated ROL and that can be rescued by feeding a ROL-free diet. We also identified that gene expression is regulated by forkhead box O (FOXO) transcription factors, which are inactivated by hyperactive Akt in the -deficient mouse RPE. Together, our findings suggest that a homeostatic pathway comprising PTEN, FOXO, and RDH can protect the RPE from ROL toxicity.