Faith A Kwa1,2, Nabeela K Dulull1, Ute Roessner3, Daniel A Dias1, Thusitha W Rupasinghe3. 1. Discipline of Laboratory Medicine, School of Health and Biomedical Sciences, Royal Melbourne Institute of Technology University, Bundoora, Victoria, 3083, Australia. 2. Department of Health Sciences and Biostatistic, School of Health and Biomedical Sciences, Swinburne University of Technology, Victoria 3122, Australia. 3. Metabolomics Australia, School of BioSciences, The University of Melbourne, Parkville, Victoria, 3010, Australia.
Abstract
Background: Age-related macular degeneration (AMD) is a leading cause of blindness in the ageing population. Without effective treatment strategies that can prevent disease progression, there is an urgent need for novel therapeutic interventions to reduce the burden of vision loss and improve patients' quality of life. Dysfunctional innate immune responses to oxidative stress observed in AMD can be caused by the formation of oxidised lipids, whilst polyunsaturated fatty acids have shown to increase the risk of AMD and disease progression in affected individuals. Previously, our laboratory has shown that the vegetable-derived isothiocyanate, L-sulforaphane (LSF), can protect human adult pigment epithelial cells from oxidative damage by upregulating gene expression of the oxidative stress enzyme Glutathione-S-Transferase µ1. This study aims to validate the protective effects of LSF on human retinal cells under oxidative stress conditions and to reveal the key players in fatty acid and lipid metabolism that may facilitate this protection. Methods: The in vitro oxidative stress model of AMD was based on the exposure of an adult retinal pigment epithelium-19 cell line to 200µM hydrogen peroxide. Percentage cell proliferation following LSF treatment was measured using tetrazolium salt-based assays. Untargeted fatty acid profiling was performed by gas chromatography-mass spectrometry. Untargeted lipid profiling was performed by liquid chromatography-mass spectrometry. Results: Under hydrogen peroxide-induced oxidative stress conditions, LSF treatment induced dose-dependent cell proliferation. The key fatty acids that were increased by LSF treatment of the retinal cells include oleic acid and eicosatrienoic acid. LSF treatment also increased levels of the lipid classes phosphatidylcholine, cholesteryl ester and oxo-phytodienoic acid but decreased levels of phosphatidylethanolamine lipids. Conclusions: We propose that retinal cells at risk of oxidative damage and apoptosis can be pre-conditioned with LSF to regulate levels of selected fatty acids and lipids known to be implicated in the pathogenesis and progression of AMD. Copyright:
Background: Age-related macular degeneration (AMD) is a leading cause of blindness in the ageing population. Without effective treatment strategies that can prevent disease progression, there is an urgent need for novel therapeutic interventions to reduce the burden of vision loss and improve patients' quality of life. Dysfunctional innate immune responses to oxidative stress observed in AMD can be caused by the formation of oxidised lipids, whilst polyunsaturated fatty acids have shown to increase the risk of AMD and disease progression in affected individuals. Previously, our laboratory has shown that the vegetable-derived isothiocyanate, L-sulforaphane (LSF), can protect human adult pigment epithelial cells from oxidative damage by upregulating gene expression of the oxidative stress enzyme Glutathione-S-Transferase µ1. This study aims to validate the protective effects of LSF on human retinal cells under oxidative stress conditions and to reveal the key players in fatty acid and lipid metabolism that may facilitate this protection. Methods: The in vitro oxidative stress model of AMD was based on the exposure of an adult retinal pigment epithelium-19 cell line to 200µM hydrogen peroxide. Percentage cell proliferation following LSF treatment was measured using tetrazolium salt-based assays. Untargeted fatty acid profiling was performed by gas chromatography-mass spectrometry. Untargeted lipid profiling was performed by liquid chromatography-mass spectrometry. Results: Under hydrogen peroxide-induced oxidative stress conditions, LSF treatment induced dose-dependent cell proliferation. The key fatty acids that were increased by LSF treatment of the retinal cells include oleic acid and eicosatrienoic acid. LSF treatment also increased levels of the lipid classes phosphatidylcholine, cholesteryl ester and oxo-phytodienoic acid but decreased levels of phosphatidylethanolaminelipids. Conclusions: We propose that retinal cells at risk of oxidative damage and apoptosis can be pre-conditioned with LSF to regulate levels of selected fatty acids and lipids known to be implicated in the pathogenesis and progression of AMD. Copyright:
Authors: Yuko Yamada; Jane Tian; Yanqin Yang; Roy G Cutler; Tinghuai Wu; Richard S Telljohann; Mark P Mattson; James T Handa Journal: J Neurochem Date: 2008-01-07 Impact factor: 5.372
Authors: Alan D Dangour; Elizabeth Allen; Diana Elbourne; Nicky Fasey; Astrid E Fletcher; Pollyanna Hardy; Graham E Holder; Rosemary Knight; Louise Letley; Marcus Richards; Ricardo Uauy Journal: Am J Clin Nutr Date: 2010-04-21 Impact factor: 7.045
Authors: Elisabeth M van Leeuwen; Eszter Emri; Benedicte M J Merle; Johanna M Colijn; Eveline Kersten; Audrey Cougnard-Gregoire; Sascha Dammeier; Magda Meester-Smoor; Frances M Pool; Eiko K de Jong; Cécile Delcourt; Eduardo Rodrigez-Bocanegra; Marc Biarnés; Philip J Luthert; Marius Ueffing; Caroline C W Klaver; Everson Nogoceke; Anneke I den Hollander; Imre Lengyel Journal: Prog Retin Eye Res Date: 2018-05-04 Impact factor: 21.198