Glycoxidized particles mimic lipofuscin accumulation in aging eyes: a new age-related macular degeneration model in rabbits.
OBJECTIVE
The biogenesis of drusen, a hallmark of age-related macular degeneration (AMD), is still unclear. Lipofuscin, which extensively accumulates with age in RPE cells, is hardly soluble, derived in part from oxidation byproducts of the photoreceptor outer segments. The purpose of the current study is to develop a new AMD model in rabbits using glycoxidized particles as imitation lipofuscin, and determine whether accumulation of lipofuscin as insoluble material may play a role in drusen biogenesis and other pathogenesis of AMD.


METHODS
To mimic the accumulation of insoluble lipofuscin, glycoxidized microspheres (glycox-MS) were made through a glycoxidation process with albumin and glycolaldehyde, alpha-hydroxy aldehyde. As a control, microspheres made with glutaraldehyde (cMS) and soluble glycoxidized (glycox-) albumin were prepared. Each material was implanted into the subretinal space in rabbits. The implanted area was assessed by funduscopy, fluorescein angiography, histology, and transmission electron microscopy (TEM).


RESULTS
Compared with control microspheres, glycox-MS stagnated for a prolonged period in the cytoplasm of RPE cells. Eyes implanted with glycox-MS produced drusen-like deposits at a significantly higher frequency, when compared with the controls. Glycox-MS were observed at the margin of or beneath the drusen-like deposits in all cases. In some eyes with glycox-MS, late-onset sub-RPE choroidal neovascularization was observed, while control groups did not have these findings.


CONCLUSIONS
These results suggest that the accumulation of indigestible granules such as lipofuscin in RPE or subsequent depositions toward Bruch's membrane may play a role in drusen biogenesis as a trigger of inflammation or via other mechanisms. This model of AMD may be useful to elucidate drusen biogenesis and pathogenesis of AMD.
Yasukawa
Tsutomu
T
Department of Ophthalmology and Eye Clinic, University of Leipzig Medical Faculty, Leipzig, Germany. yasukawa@med.nagoya-cu.ac.jp
Wiedemann
Peter
P
Hoffmann
Stefan
S
Kacza
Johannes
J
Eichler
Wolfram
W
Wang
Yu-Sheng
YS
Nishiwaki
Akiko
A
Seeger
Johannes
J
Ogura
Yuichiro
Y
D000375:Aging; D000818:Animals; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D017127:Glycation End Products, Advanced / Q000378:metabolism; D008062:Lipofuscin / Q000378:metabolism*; D008268:Macular Degeneration / Q000378:metabolism* / Q000473:pathology; D008863:Microspheres; D010084:Oxidation-Reduction; D011817:Rabbits; D012160:Retina / Q000378:metabolism* / Q000648:ultrastructure; D015593:Retinal Drusen / Q000378:metabolism / Q000473:pathology; D012709:Serum Albumin / Q000378:metabolism*; D000093423:Glycated Serum Albumin
D017127:Glycation End Products, Advanced; D008062:Lipofuscin; D012709:Serum Albumin; D000093423:Glycated Serum Albumin