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P.K. Russ, B.C. Lee, M. Chang, M. Kuro–o, F.R. Haselton; Retinal Pathology in EFmKL46 Klotho Overexpressing Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5778.
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The purpose of this work is to characterize the retinal pathology present in EFmKL46 kloth overexpressing mice. Klotho is a novel protein that has recently been shown to inhibit insulin/IGF–1 signaling (H. Kurosu, et al., Science, 2005 Sep 16), and when overexpressed in mice extends the animals' lifespan. However, the EFmKL46 mice also have significant retinal degeneration when compared to age and sex matched wild type animals.
EFmKL46 klotho overexpressing mice provided by Dr. Kuro–o were initially screened for retinal vascular pathology using fluorescein angiography. Fundus photography was used to identify non–vascular lesions, and electroretinograms were performed to assess function. Finally, histological sections were examined to confirm the pathology observed with the in vivo assays.
Fundus photography showed areas of retinal hyper and hypopigmentation as well as possible scarring and exudates. Fluorescein angiography revealed significant vascular abnormalities. There were small hemorhages, retinal branch vein occlusions, and possible areas of neovascularization. Electroretinograms indicated a significant loss of function. Histological sections indicate that this is likely due to the loss of photoreceptors as well as significant loss in the outer nuclear layer.
These klotho overexpressing mice have significant retinal pathology which needs to be further studied to determine the underlying cause of the observed pathology.
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