title: Potential protective function of the sterol regulatory element binding factor 1-fatty acid desaturase 1/2 axis in early-stage age-related macular degeneration.
abstract: Age-related macular degeneration (AMD) is the most common cause of vision loss in elderly individuals throughout the developed world. Inhibitors of vascular endothelial growth factor have been successfully used to treat choroidal neovascularization in late-stage AMD. The pathogenesis of early-stage AMD, however, remains largely unknown, impairing efforts to develop effective therapies that prevent progression to late-stage AMD. To address this, we performed comparative transcriptomics of macular and extramacular retinal pigmented epithelium-choroid (RPE-choroid) tissue from early-stage AMD patients. We found that expression of fatty acid desaturase 1 (FADS1),FADS2, and acetyl-CoA acetyltransferase 2 (ACAT2) is increased in macular but not extramacular tissue, possibly through activation of sterol regulatory element binding factor 1 (SREBF1). Consistent with this, we also found that expression ofFads1is increased in RPE-choroid in a mouse model of early-stage AMD. In zebrafish, deletion offads2, which encodes a protein that functions as both Fads1 and Fads2 in other species, enhanced apoptosis in the retina upon exposure to intense light. Similarly, pharmacological inhibition of Srebf1 enhanced apoptosis and reducedfads2expression in zebrafish exposed to intense light. These results suggest that the SREBF1-FADS1/2 axis may be activated in macular RPE-choroid as a protective response during early-stage AMD and could thus be a therapeutic target for early-stage AMD.
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ashikawa
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Tsu, Mie, Japan; Department of Systems Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie, Japan; Mie University Medical Zebrafish Research Center, Tsu, Mie, Japan; Department of Omics Medicine, Mie University Industrial Technology Innovation Institute, Tsu, Mie, Japan; Department of Bioinformatics, Mie University Life Science Research Center, Tsu, Mie, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Shiko
authors.initials: S
authors.lastname: Okabe
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Mizuki
authors.initials: M
authors.lastname: Yuge
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tada
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Miyao
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Soichiro
authors.initials: S
authors.lastname: Murakami
authors.affiliation: Department of Systems Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Koki
authors.initials: K
authors.lastname: Kawaguchi
authors.affiliation: Department of Systems Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Sasagawa
authors.affiliation: Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Tsu, Mie, Japan; Department of Systems Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie, Japan; Mie University Medical Zebrafish Research Center, Tsu, Mie, Japan; Department of Omics Medicine, Mie University Industrial Technology Innovation Institute, Tsu, Mie, Japan; Department of Bioinformatics, Mie University Life Science Research Center, Tsu, Mie, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Department of Systems Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie, Japan; Mie University Medical Zebrafish Research Center, Tsu, Mie, Japan; Department of Omics Medicine, Mie University Industrial Technology Innovation Institute, Tsu, Mie, Japan; Department of Bioinformatics, Mie University Life Science Research Center, Tsu, Mie, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Tanaka
keywords: Ophthalmology; Pharmaceutical science