title: Glycoxidized particles mimic lipofuscin accumulation in aging eyes: a new age-related macular degeneration model in rabbits.
abstract: 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.
authors.affiliation: Department of Ophthalmology and Eye Clinic, University of Leipzig Medical Faculty, Leipzig, Germany. yasukawa@med.nagoya-cu.ac.jp
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yasukawa
authors.forename: Peter
authors.initials: P
authors.lastname: Wiedemann
authors.forename: Stefan
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Johannes
authors.initials: J
authors.lastname: Kacza
authors.forename: Wolfram
authors.initials: W
authors.lastname: Eichler
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Wang
authors.forename: Akiko
authors.initials: A
authors.lastname: Nishiwaki
authors.forename: Johannes
authors.initials: J
authors.lastname: Seeger
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Ogura
mesh_terms: 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
chemical_list: D017127:Glycation End Products, Advanced; D008062:Lipofuscin; D012709:Serum Albumin; D000093423:Glycated Serum Albumin