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D. W. Leung, G. P. Vissvesvaran, L. A. Lindlief, M. Kamat, K. Murata, R. Kubota, A. Fawzi; Effect of the Aroylhydrazone Class of Iron Chelators on Photoreceptor and Retinal Pigment Epithelial Cells Against Light, A2E or Oxidative Stress. Invest. Ophthalmol. Vis. Sci. 2007;48(13):43.
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© ARVO (1962-2015); The Authors (2016-present)
Iron accumulation in retina has been indicated to play a role in the pathogenesis of age-related macular degeneration (AMD). Salicylaldehyde isonicotinoyl hydrazone has been found to be the most effective iron chelator in protecting retinal pigment epithelial (RPE) cells against oxidative stress (Amado et al., ARVO 2006). The aim of the present study is to determine if this class of aroylhydrazone molecules are also effective in protecting primary photoreceptors in culture from light or oxidative stress and RPE cells from A2E plus light stress.
Primary retinal cell cultures (10-14 days in culture) prepared from Bovine retinas were pretreated with different concentrations of aroylhydrazone compounds overnight, cells were then treated with 1 mM tertiary butyl hydroperoxide (tBOOH) or exposed to blue light (500 lux, 420 nm, 1.1 mW/cm2) for 20 hours. Cells were stained with Sytox Green to assess the extent of cell death. Photoreceptor cells were counted after immunolabeling with recoverin antibodies. ARPE-19 cells were preloaded with 10 µM A2E, pretreated with test compounds and exposed to light prior to assays for cell death.
1 mM tBOOH induced 100% death of photoreceptors, whereas twenty hours exposure to blue light at 500 lux induced 70% death of photoreceptors in bovine retinal cell cultures. Some aroylhydrazones protected 100% of photoreceptors against tBOOH induced oxidative stress at < 10 µM. However, none of the compounds at similar concentrations were able to protect retinal photoreceptors against blue-light-mediated damage by > 30%. A few of these compounds were found to protect by > 50% ARPE-19 cells pretreated with 10 µM A2E and exposed to blue light.
These data show that some aroylhydrazone compounds are effective in protecting photoreceptor cells against oxidative stress, but not against light stress, suggesting that the mechanism of cell death induced by these two stresses are somewhat different. These compounds were more effective in protecting ARPE-19 cells pretreated with A2E than photoreceptors against light stress. As it is known that protection of RPE cells can lead to protection of photoreceptors in vivo, aroylhydrazone compounds may be viable candidates for AMD indications.
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