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C. King, P. Krajacic, Y. Qian, T. Dentchev, N. Ligato, P. Hahn, J.L. Dunaief; Retinal Degeneration and Neovascularization in Iron Overloaded Cp/Heph Deficient Mice is Exacerbated by Bright Light Exposure and Aging . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2592.
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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 the cell 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 exposure exacerbates the retinal degeneration. Further, to determine whether the retinal degeneration would worsen with age, we studied retinas of the oldest surviving Cp/Heph–deficient mouse, which was one year old.
C57BL/6 Cp/Heph–deficient and control mice, all 5 months old, were exposed for either 7 hours or 7 days to 10,000 lux constant cool white fluorescent light in a well–ventilated apparatus. Mice were euthanized 10 days after light damage and eyes were prepared for plastic and cryo sectioning. Retinas from the one year old Cp/Heph–deficient mouse were also studied histologically.
Several foci of subretinal neovascularization were present in Cp/Heph–deficient but not control C57BL6 mice exposed to 7 hrs of bright light. Age–matched Cp/Heph–deficient mice not exposed to light had no subretinal neovascularization. 7 days of light exposure resulted in significant photoreceptor thinning in Cp/Heph–deficient but not control mice. The one year old Cp/Heph–deficient mouse displayed multiple foci of subretinal neovascularization, photoreceptor layer thinning, and RPE hypertrophy. Cellular infiltrate was also found in the photoreceptor layer of the one year old mouse.
These preliminary data imply that light exposure may hasten the retinal degeneration seen in aging Cp/Heph–deficient mice. Light exposure may potentiate iron induced oxidative stress. Additional experiments will be performed to measure the levels of oxidative stress in Cp/Heph–deficient retinas at different ages and following bright light exposure. Immunohistochemistry will be performed to ascertain the identity of the infiltrating cells.
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