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Bogale Aredo, Hua Lu, Kaiyan Zhang, Cynthia Wang, Rafael Ufret-Vincenty; Effect Of Hydroquinone And Increased Light Exposure On The CfhTg Model Of Early Amd. Invest. Ophthalmol. Vis. Sci. 2011;52(14):965.
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The 402H variant of complement factor H (Cfh; a key regulator of complement activation) increases the risk of AMD up to 7-fold. Cigarette smoking is a major environmental risk factor for AMD. In this study, we are determining the effect of hydroquinone (HQ, a major component in cigarette smoke), alone or in combination with light exposure, on the AMD-like changes in Cfh transgenic (CfhTg) mice expressing the 402H variant. We hypothesize that the interaction between this Cfh-genotype and pro-oxidative environmental insults can lead to the development of an AMD-like phenotype.
We generated a transgene consisting of human Cfh SCR6-8 flanked by mouse Cfh SCR1-5 and SCR9-20 (under the ApoE promoter). The resulting chimeric CfhTg mice were crossed to mCfhKO mice (deficient on mouse Cfh). We fed grain-based rodent diet containing 0.8% HQ (Sigma) to 24 CfhTg/mCfhKO mice and 26 age-matched B6 mice. Of these, 15 CfhTg/mCfhKO and 16 B6 mice were kept under increased light (special room with direct illumination at 5000-Lux) while the rest were kept under regular light intensity. Control mice that received control diet and normal illumination included 9 transgenic and 9 B6 mice. All mice were on a 12 h light-12 h dark cycle. Analysis of retinal fundus photos, RPE/choroid flat mounts, immunohistochemistry and electron microscopy (EM) was done.
Fundus photographs were obtained at an early time-point (2 m after starting the diet/light exposure) and surprisingly, the transgenic mice showed a significantly higher number of yellow spots in their retinas. We will report and compare the 6 month results on the fundus appearance (yellow spots and pigmentary changes), histopathology, immunohistochemistry (C3d deposition), and EM (basal laminar deposits) in CfhTg/mCfhKO vs. B6 mice that have been exposed to HQ and increased light.
Exposure of CfhTg/mCfhKO mice to HQ and increased light may lead to a model for early AMD based on relevant genetic and environmental risk factors.
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