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Glycoxidized particles mimic lipofuscin accumulation in aging eyes: a new age-related macular degeneration model in rabbits

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Abstract

Purpose

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, α-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.

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Acknowledgements

Tsutomu Yasukawa, MD, conducted the present study as an Alexander von Humboldt Foundation scholar. We thank Grit Müller for help with animal surgery and Ute Weinbrecht, Karin Bartholomäus, and Silke Jantzen for technical assistance.

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Authors and Affiliations

  1. Department of Ophthalmology and Eye Clinic, University of Leipzig Medical Faculty, Leipzig, Germany

    Tsutomu Yasukawa, Peter Wiedemann, Stefan Hoffmann, Wolfram Eichler, Yu-Sheng Wang & Akiko Nishiwaki

  2. Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya-shi, Aichi, 467-8601, Japan

    Tsutomu Yasukawa, Akiko Nishiwaki & Yuichiro Ogura

  3. Institute of Veterinary Anatomy, University of Leipzig, Leipzig, Germany

    Johannes Kacza & Johannes Seeger

  4. Department of Ophthalmology, the Xijing Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China

    Yu-Sheng Wang

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  1. Tsutomu Yasukawa
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  2. Peter Wiedemann
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Correspondence to Tsutomu Yasukawa.

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Supported in part by German Research Community (DFG) grant WI 880/9-1.

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Yasukawa, T., Wiedemann, P., Hoffmann, S. et al. Glycoxidized particles mimic lipofuscin accumulation in aging eyes: a new age-related macular degeneration model in rabbits. Graefes Arch Clin Exp Ophthalmol 245, 1475–1485 (2007). https://doi.org/10.1007/s00417-007-0571-z

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