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H Ida, N Miyamura, S Honda, TM Blankenship, JT Handa, LM Hjelmeland; Ultrastructural Aging of Bruch's Membrane in D-galactose Induced Aging Mouse Model . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2790.
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Purpose:Our laboratory has demonstrated advanced glycation endproduct (AGE) mediated aging to the retinal pigment epithelium (RPE) and Bruch's membrane as it relates to age-related macular degeneration (AMD). Subcutaneous D-galactose injections below a level that simulates diabetes mellitus induce AGE-related systemic aging to C57BL/6J mice. The purpose of this study was to identify in this model, ultrastructural aging to the RPE-Bruch's membrane complex. Methods:5 or 18 month C57BL/6J mice were given daily 50 mg/kg D-galactose or PBS subcutaneous injections for 8 weeks. Immediately (n=5), 1 (n=5), and 2 (n=5) months after treatment, mice were sacrificed. Eyes were fixed in 2.5% glutaraldehyde, 2.0% paraformaldehyde in 0.08M cacodylate, post-fixed in 1% osmium tetroxide/0.1M cacodylate, embedded in epoxy resin, and ultrathin sections were prepared for transmission electron microscopy. Results:The RPE-Bruch's membrane complex of PBS-treated 5 month mice had normal morphological and ultrastructural characteristics. The RPE-Bruch's membrane complex of D-galactose treated mice showed progressive changes with time. Immediately after treatment, mildly increased RPE basolateral infoldings, small basal laminar deposits (BlamD; deposits between the RPE and RPE basement membrane), and abnormal appearing collagen in the collagenous layers were seen. These changes were more prominent one and two months after treatment. The changes seen 2 months post-treatment were similar to 20 month old PBS treated controls. Conclusion:Low dose D-galactose injections induce aging related changes to the RPE and Bruch's membrane that could simulate changes seen in age-related macular degeneration.
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