dark controls) were quantified per sample. == Lipid peroxidation assays == The Lipid Peroxidation (MDA) Assay Package (Colorimetric/Fluorometric) (Abcam, Cat# ab118970) was used as per the manufacturers instructions. synergistic with dietary antioxidant supplementation. == Neuroscience: Vision is stress filled for aged flies == Paradoxically, light is essential to get vision, yet it also induces stress that damages the sensitive cells in the eye. Vikki Weake and her group at Purdue University analyzed how exposure to blue light causes damage to the retina in fruit flies. Blue light causes death of photoreceptors, the light-sensing neurons. Surprisingly, very young flies are resistant to blue light. Increasing levels BMS-983970 of a single protein, Cytochrome-b5, mimicked youthful resilience in older flies. Cytochrome-b5 is central to an ancient cellular defense system that protects membranes from oxidative damage. With expansive sensory membranes containing BMS-983970 specialized lipids, photoreceptors are especially sensitive to membrane lipid peroxidation, an emerging final common pathway for cell death in aging and disease. Research into preventing lipid peroxidation might help to develop therapies for age-related diseases such as age-related macular degeneration. == Introduction == During ageing, weakened antioxidant defenses allow accumulation of toxic reactive oxygen species (ROS) that contribute to ageing, and to multiple diseases, including cancer, neurodegeneration and age-related macular degeneration (AMD). 15Once initiated by any of several pathways, lipid peroxidation, oxidative damage of membrane lipids, spreads aggressively in a self-propagating chain reaction, amplifying oxidative damage. 6Lipid peroxides adversely alter membrane structure and function and generate highly reactive toxic secondary products that react with proteins and DNA, compromising normal BMS-983970 activity. 6The retina is uniquely at risk for lipid peroxidation because of its high concentration of peroxidation-sensitive polyunsaturated fatty acids, and energy-intensive, oxygen-rich environment. 4Multiple pathways, including photodynamic generation of ROS by rhodopsin and associated metabolites, translate light into retinal oxidative stress; 7constant light causing photoreceptor degeneration in rat retina generates lipid peroxides in photosensory outer segment membranes. 8Antioxidants that terminate radical propagation, such as vitamin E, or glutathione peroxidases that reduce lipid peroxides form the major defense mechanisms against lipid peroxidation6and antioxidant supplements are the standard of care to slow AMD progression. 9However, antioxidant supplements do not halt AMD progression, 9and antioxidant therapy has not shown positive results in intervention trials for other neurodegenerative diseases involving oxidative stress. 5, 10Identifying factors that enhance the ability of neurons to cope with oxidative stress could provide therapeutic avenues for age-related neurodegenerative diseases, including AMD. Here, we describe an acute phototoxicity model in the fruitfly, Drosophila melanogaster, in which blue light exposure induces phototransduction-dependent oxidative stress, lipid peroxidation and retinal degeneration. We identify Cyt-b5 as a neuroprotective factor that prevents retinal degeneration by suppressing light-stress-induced GMCSF lipid peroxidation. Cyt-b5 partners with Cyt-b5 reductase to form the plasma membrane redox system, an ancient front line defense against lipid peroxidation. 2Thus, potentiation of the plasma membrane redox system via targeted Cyt-b5 expression offers a strategy, potentially synergistic with dietary antioxidants, to delay the onset or progression of age-related neurodegenerative diseases involving lipid peroxidation. == Results == To establish conditions that reliably elicited photoreceptor degeneration in response to light stress, we exposed flies to regimes of varying light intensity and duration at different ages and examined their eyes post-exposure using confocal and electron microscopy (Fig. 1a). As flies lacking normal eye screening pigment are sensitized to light damage, 11we used white-eyed (w1118) flies. We found eight hours of strong blue light (= 465 nm) caused loss of the photosensory membrane organelle (rhabdomere) in fewer than 1% of photoreceptors in 1-day-old flies (1219 h post-eclosion), but 17% and 62% by 3 and 6 days of age respectively (Fig. 1b, c). We previously showed that exposure to similar intensities of red light did not induce retinal.