LIGHT-INDUCED PHOTORECEPTOR AND RPE DEGENERATION: PROTECTION BY PYRUVATE, NICOTINAMIDE, OR CYCLIC LIGHT AGANIST ZINC TOXICITY
Document Type
Presentation
Start Date
22-10-2010 10:45 AM
End Date
22-10-2010 12:00 PM
Description
Purpose: Light-induced retinal damage (LO) can be a problem after surgery, and sun exposure. Intense light which serves as a oxidative model causes preferential photoreceptor death in the superior central retina of albino mice and rats, Previous work on retinal ischemia induced neuronal death suggests the involvement of Zn2+ toxicity in the death of retinal cell layers, and demonstrates the efficacy of pyruvate. Here, we show a role for Zn2+ in oxidative stress and light induced damage in vitro and in vivo.
Methods: Muller, ARPE-19 cells and a cone photoreceptor-derived 'line were exposed to Zn2+, and oxidative stress (OS) and the efficacy of pyruvate, nicotinamide, and NAO+ were determined. Spague-Dawley albino rats were exposed to 18klux of white fluorescent light for 1-4 hours in the presence or absence of pyruvate, nicotinamide, lactate, or cyclic light. The intracellular free zinc concentration, ([Zn2+]1), and cell damage were assessed after certain time.
Results: We show that Zn2+, and OS results in increased [Zn2+]1, and that Zn2+ therapeutic compounds (pyruvate, nicotinamide, and NAO+) and inhibitors of previously implicated pathways (sirtuin) are efficacious in vitro. In vivo, exposure to 18 klux of cool white fluorescent light for 1 hour induced a large increase in Zn2+ staining at 4-14 hours which was prior to cell death at 36-48 hours, particularly in the superior outer nuclear layer (ONL) and RPE of dark-maintained Sprague-Dawley albino rats; 4 hours of light was required to induce similar damage in cyclic lightmaintained rats. Nicotinamide and pyruvate (i.p.), but not lactate, attenuated this death, as measured using Optical Coherence Tomography (OCT) and confirmed by counting photoreceptor nuclei.
Conclusions: Zn2+ plays a role in this injury, as suggested by the increased Zn2+ staining and the efficacy of Zn2+ therapeutics. These results suggest that cyclic light maintenance, Zn2+ chelation, pyruvate, and nicotinamide promote RPE and photoreceptor survival after injury, and could be effective for various forms of retinal neurodegeneration. These results could have immediate clinical applications in surgery-, or sun exposure-induced light damage to the retina.
Recommended Citation
Bai, Shi; Sheline, C. T.; and Zhou, Y., "LIGHT-INDUCED PHOTORECEPTOR AND RPE DEGENERATION: PROTECTION BY PYRUVATE, NICOTINAMIDE, OR CYCLIC LIGHT AGANIST ZINC TOXICITY" (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 3.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/poster1/3
LIGHT-INDUCED PHOTORECEPTOR AND RPE DEGENERATION: PROTECTION BY PYRUVATE, NICOTINAMIDE, OR CYCLIC LIGHT AGANIST ZINC TOXICITY
Purpose: Light-induced retinal damage (LO) can be a problem after surgery, and sun exposure. Intense light which serves as a oxidative model causes preferential photoreceptor death in the superior central retina of albino mice and rats, Previous work on retinal ischemia induced neuronal death suggests the involvement of Zn2+ toxicity in the death of retinal cell layers, and demonstrates the efficacy of pyruvate. Here, we show a role for Zn2+ in oxidative stress and light induced damage in vitro and in vivo.
Methods: Muller, ARPE-19 cells and a cone photoreceptor-derived 'line were exposed to Zn2+, and oxidative stress (OS) and the efficacy of pyruvate, nicotinamide, and NAO+ were determined. Spague-Dawley albino rats were exposed to 18klux of white fluorescent light for 1-4 hours in the presence or absence of pyruvate, nicotinamide, lactate, or cyclic light. The intracellular free zinc concentration, ([Zn2+]1), and cell damage were assessed after certain time.
Results: We show that Zn2+, and OS results in increased [Zn2+]1, and that Zn2+ therapeutic compounds (pyruvate, nicotinamide, and NAO+) and inhibitors of previously implicated pathways (sirtuin) are efficacious in vitro. In vivo, exposure to 18 klux of cool white fluorescent light for 1 hour induced a large increase in Zn2+ staining at 4-14 hours which was prior to cell death at 36-48 hours, particularly in the superior outer nuclear layer (ONL) and RPE of dark-maintained Sprague-Dawley albino rats; 4 hours of light was required to induce similar damage in cyclic lightmaintained rats. Nicotinamide and pyruvate (i.p.), but not lactate, attenuated this death, as measured using Optical Coherence Tomography (OCT) and confirmed by counting photoreceptor nuclei.
Conclusions: Zn2+ plays a role in this injury, as suggested by the increased Zn2+ staining and the efficacy of Zn2+ therapeutics. These results suggest that cyclic light maintenance, Zn2+ chelation, pyruvate, and nicotinamide promote RPE and photoreceptor survival after injury, and could be effective for various forms of retinal neurodegeneration. These results could have immediate clinical applications in surgery-, or sun exposure-induced light damage to the retina.