Ultrastructural aging of the RPE-Bruch's membrane-choriocapillaris complex in the D-galactose-treated mouse.
OBJECTIVE
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.
Ida
Hisashi
H
Department of Ophthalmology, UC Davis, California, USA.
Ishibashi
Kazuki
K
Reiser
Karen
K
Hjelmeland
Leonard M
LM
Handa
James T
JT
D019588:Aging, Premature / Q000139:chemically induced / Q000473:pathology*; D000818:Animals; D016570:Bruch Membrane / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D002196:Capillaries / Q000648:ultrastructure; D002829:Choroid / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005690:Galactose / Q000633:toxicity*; D017127:Glycation End Products, Advanced / Q000378:metabolism; D015227:Lipid Peroxidation; D051379:Mice; D008810:Mice, Inbred C57BL; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D013050:Spectrometry, Fluorescence
D017127:Glycation End Products, Advanced; D005690:Galactose