The klotho-overexpressing mouse, EFmKL46, is an animal model of insulin resistance that is not hyperglycemic. In this study, the retinopathy associated with altered insulin signaling in this transgenic animal is evaluated.
In four young (8-16 weeks) and 12 aged (70-80 weeks) EFmKL46 mice and age/ sex matched wild type controls, the retinal vasculature was visualized by fluorescence angiography and fundus photography. Photoreceptor function was evaluated by electroretinography (ERG). Tissue sections from post-mortem retinas were histologically examined for retinal layer anomalies and degeneration. Immunohistochemisty was used to visualize the klotho protein in mouse retinas and human retinal pigment epithelium (RPE) cells. Aged EFmKL46 mice had abnormal retinal vasculature including tortuous veins, hemorrhages, and microaneurysms. Hypo/hyperpigmentation of the retina and possible retinal scarring and exudates were observed. ERG analysis showed decreased a/b-wave amplitudes. Histological examination showed a wavy photoreceptor-RPE interface and photoreceptor degeneration which ranged from outer segment loss to the complete deterioration of the photoreceptor layer. In aged EFmKL46 mice with complete photoreceptor loss, the RPE was thickened and showed areas of proliferation. Outer retinal layers were destroyed. Antibodies indicated klotho was present throughout the retina and human RPE cells. No retinal anomalies were observed in young EFmKL46 and young and aged wild type mice. In conclusion, the nonhyperglycemic, klotho-overexpressing mouse has retinal pathologies consistent with those seen in other animal models of insulin-dependent and insulin-resistant diabetes and is a promising tool for more detailed studies of pathologies associated with insulin signaling dysfunction.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-07202006-091901 |
| Date | 20 July 2006 |
| Creators | Lee, Brittany Celeste |
| Contributors | Dr. Patricia K. Russ, Dr. Frederick R. Haselton |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-07202006-091901/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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