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S.-H. Min, R. Miller, Y.-K. Choi, S. Song, V. Chiodo, M. Kuro-O, W. W. Hauswirth; Expression of Klotho and Its Possible Role in a Visual Function of Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):784. doi: https://doi.org/.
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A deficit in Klotho gene expression in the knock-out mouse (KL(-/-)) results in a multiple age-related disorders, including a short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis and emphysema. Many of these symptoms are also seen in the aging human. The gene encodes both secreted and membrane-associated forms, and the membrane form is found in multiple tissues, particularly in the kidney. Given the fact that Klotho has a potential role in the aging process of multiple organs, we tested whether and where this gene is expressed in retina, one of the most age-sensitive organs.
Retinas of KL(-/-) mice were harvested and Klotho RNA analyzed by RT-PCR using primers specific for both membrane and secreted forms of the protein. The retina was also subjected to immunohistochemical analysis using monoclonal antibody against the membrane form. Finally, ERG analysis was carried out on KL(-/-) mice at 1, 2, and 3 months of age to elucidate a possible role for Klotho in the aging retina.
RT-PCR showed that both secreted- and membrane associated forms of Klotho were expressed in retinas of KL(-/-) mice. Immunohistochemical analysis revealed the presence of the membrane-bound protein in several layers of the retina, most abundantly within retinal ganglion cells (RGCs) and photoreceptors. ERG analysis demonstrated that both scotopic a-and b-wave amplitudes were severely decreased in Klotho-KO mice relative to wild type mice as they age, with an almost unrecordable ERG response by 3 months of age.
We were able to detect expression of both secreted and membrane-associated Klotho in the mouse retina. with immunohistochemical studies showing Klotho present predominantly in RGCs and photoreceptors. These observations raise the possibility that the Klotho gene may possess a functional role in the retina. Consistent with this suggestion, the rod-mediated ERG response in KL(-/-) mice was substantially decreased at all ages up to 3 months relative to normal mice. At that age KL(-/-) mice are near the end of their life and exhibit only a residual ERG signal.
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