May 2016
Volume 57, Issue 6
Open Access
Research Highlight  |   May 2016
RACking Up Retinal Oxidative Stress
Author Affiliations
  • Joshua L. Dunaief
    Adele Niessen Professor of Ophthalmology University of Pennsylvania, Philadelphia, Pennsylvania, United States;
Investigative Ophthalmology & Visual Science May 2016, Vol.57, 2876. doi:
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      Joshua L. Dunaief; RACking Up Retinal Oxidative Stress. Invest. Ophthalmol. Vis. Sci. 2016;57(6):2876. doi:

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      © ARVO (1962-2015); The Authors (2016-present)

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It is well established that oxidative stress can potentiate retinal disease and that antioxidants and iron chelators can be protective, but in this issue, Song et al.1 present a novel mechanism of retinal oxidative stress. They show using in vivo mouse overexpression studies that the small GTPase RAC1 (Ras-related C3 botulinum toxin substrate 1) can induce photoreceptor death by increasing oxidative stress. RAC1 is a known activator of NOX (NADPH oxidases), which in turn produce superoxide. In rho-RAC1 transgenic mice, oxidative stress is increased, as measured with Dihydroethidium (DHE) labeling and protein carbonyl measurement in Western analysis. Photoreceptors subsequently degenerate, but can be rescued with daily intraperitoneal injections of the NOX inhibitor apocyanin. Also, adeno-associated virus (AAV)-rho-RAC1 induces photoreceptor death when injected into adult mouse eyes. This study, in combination with other recent publications implicating NOX-induced ROS in light damage,2 hereditary retinal degeneration,3 and retinal neovascularization,4 suggests that NOX or RAC inhibition could be therapeutically fruitful. 
Song H, Vijayasarathy C, Zeng Y, et al. NADPH oxidase contributes to photoreceptor degeneration in constitutively active RAC1 mice. Invest Ophthalmol Vis Sci. 2016; 57: 2864–2875.
Roehlecke C, Schumann U, Ader M, et al. Stress reaction in outer segments of photoreceptors after blue light irradiation. PLoS One. 2013; 8: e71570.
Usui S, Oveson BC, Lee SY, et al. NADPH oxidase plays a central role in cone cell death in retinitis pigmentosa. J Neurochem. 2009; 110: 1028–1037.
Chan EC, van Wijngaarden P, Liu GS, Jiang F, Peshavariya H, Dusting GJ. Involvement of Nox2 NADPH oxidase in retinal neovascularization. Invest Ophthalmol Vis Sci. 2013; 54: 7061–7067.

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