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A. Lipski, M. Endres, S. Skosyrski, D. Biniszkiewicz, K. Rüther; Impaired Mouse ERG Caused by DNA Repair Deficiency and Folate Restriction. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3056.
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To demonstrate the influence of DNA integrity on mouse ERG responses. The abundantly expressed enzyme uracil-DNA-glycosylase (UNG) initiates Base Excision Repair (BER) of aberrant Uracil residues in mitochondrial and nuclear DNA. In the retina, misincorporation of uracil into DNA or oxidative cytosine deamination to uracil may lead to faulty transcripts and thus to impaired protein function. For the purpose to examine the impact of altered DNA base metabolism on retinal function, we conducted electroretinograms in UNG-deficient (UNG-/-) and wildtype (UNG+/+) mice.
Ganzfeld electroretinograms were performed in UNG-/- and UNG+/+ mice. Because folate depletion is known to further increase levels of uracil in DNA, we exposed both mouse strains either to an experimental folate-deficient or control diet for 3 months before examination. Multivariance analysis was performed on the resulting ERG data.
Whereas folate restriction compared to control diet caused a significant attenuation of the ERG a-, b-, and c-wave response amplitudes, UNG-/- mice revealed a significant decrease in c-wave amplitudes compared to UNG+/+ littermates. Differences in amplitudes were most imposing between UNG+/+/control diet and UNG-/-/folate-depleted mice. Furthermore, c-wave implicit times revealed significant differences between UNG+/+/folate-deficient and UNG-/-/folate-deficient mice or UNG-/-/folate-fed mice, respectively.
Significantly different c-wave amplitudes and implicit times in UNG-/- and UNG+/+ mice point to the relevancy of DNA repair for the light-evoked changes of transmembraneous potentials at the retinal pigment epithelium. Additionally, experimental folate depletion results in pronounced attenuation of major ERG components. Further analysis of DNA repair-deficient mouse strains may uncover the probable role for DNA repair in maintaining neurosensory retinal function.
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