Purchase this article with an account.
C. King, T. Dentchev, D. Praticò, J. L. Dunaief; Oxidative Stress-Mediated Retinal Degeneration in Cp/Heph Deficient Mice Is Exacerbated by Bright Light-Exposure. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3029.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Age-related macular degeneration (AMD) is the most common cause of vision loss in the United States in those 50 or older. Iron, which can generate free radicals through the Fenton reaction, is increased in the retinal pigment epithelium (RPE), Bruch’s membrane, and photoreceptors of AMD patients. In addition, mice that lack both Ceruloplasmin (Cp) and Hephaestin (Heph), two ferroxidases necessary for cellular export of iron, display retinal iron overload and retinal degeneration with features of AMD. Since the mechanism of retinal degeneration in Cp/Heph deficient mice is most likely iron induced oxidative stress, and since light can cause photo-oxidative damage, we tested whether bright light can exacerbate retinal degeneration in Cp/Heph deficient and in Cp deficient mice. In addition, we measured isoprostane levels, which are an indicator of oxidative stress, to determine if iron can act synergistically with bright light to generate oxidative stress in vivo.
C57BL6 Cp/Heph and Cp deficient mice and wild-type mice, all 6 months old, were exposed for 5 days to 10,000 lux constant cool white fluorescent light in a well-ventilated apparatus. The mice that were used for the retinal degeneration study were euthanized 10 days after light damage and eyes were prepared for plastic and cryo sectioning. For the oxidative stress study, the mice were euthanized 24 hours after light damage and the neurosensory retinas were isolated for analysis of isoprostane levels by mass spectrometry.
5 days of light exposure resulted in significant photoreceptor thinning in Cp/Heph deficient mice but not wild-type mice. Significant increases in the number of TUNEL positive photoreceptors, presumably undergoing apoptosis, were also seen in the retinas of the Cp/Heph deficient mice after light exposure compare to the wild-type mice. The retinal isoprostane levels from the Cp/Heph deficient mice were significantly higher than in wild-type mice.
These data imply that light exposure can potentiate iron induced retinal degeneration, and that iron may act synergistically with bright light to cause oxidative stress and retinal degeneration in vivo. Strategies to decrease the levels of labile iron may prove useful in amelioration of retinal degeneration.
This PDF is available to Subscribers Only