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(Investigative Ophthalmology and Visual Science. 2004;45:2348-2354.)
© 2004 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.03-1337
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Ultrastructural Aging of the RPE–Bruch’s Membrane–Choriocapillaris Complex in the D-Galactose–Treated Mouse

Hisashi Ida,1 Kazuki Ishibashi,2 Karen Reiser,3 Leonard M. Hjelmeland,1,4 and James T. Handa2

1From the Departments of Ophthalmology, 3Neurological Surgery, and 4Molecular and Cellular Biology, UC Davis, Davis, California, and 2Michael Panitch Macular Degeneration Laboratory, Wilmer Eye Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland.

PURPOSE. Low-dose D-galactose treatment in mice induces accelerated aging due to advanced glycation endproduct (AGEs) formation. The purpose of this study was to identify ultrastructural aging in the retinal pigment epithelium (RPE)–Bruch’s membrane–choriocapillaris.

METHODS. Five-month-old C57Bl6 mice were injected daily with D-galactose or control buffer for 8 weeks. Eighteen-month-old mice were also treated with control buffer for 8 weeks. Eyes were prepared for electron microscopy and AGE-specific fluorescence at ex = 370 nm/em = 440 nm and ex = 330 nm/ex = 390 nm.

RESULTS. D-Galactose treatment induced AGE-specific fluorescence in lens and RPE/choroid compared to buffer-treated controls. In D-galactose–treated animals, the RPE had dilated and fewer basolateral infoldings. Bruch’s membrane had alterations that included significant thickening, sub-RPE and prominent outer collagenous layer deposits, and choriocapillaris basement membrane duplication/splitting and thickening. The choriocapillaris endothelium displayed fenestration loss.

CONCLUSIONS. Ultrastructural aging to the RPE–Bruch’s membrane–choriocapillaris developed in mice treated with low-dose D-galactose. These changes could contribute to age-related changes that promote early age-related disease.




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