gms | German Medical Science

102. Jahrestagung der DOG

Deutsche Ophthalmologische Gesellschaft e. V.

23. bis 26.09.2004, Berlin

Transport and accumulation of Lipofuscin fluorophore A2-E in RPE

Meeting Abstract

  • corresponding author F. Schütt - Department of Ophthalmology, University of Heidelberg, Germany
  • E. Kämmerer - Department of Molecular Pathology, University of Heidelberg, Germany
  • F. G. Holz - Department of Ophthalmology, University of Bonn, Germany
  • H. E. Völcker - Department of Ophthalmology, University of Heidelberg, Germany
  • J. Kopitz - Department of Molecular Pathology, University of Heidelberg, Germany

Evidenzbasierte Medizin - Anspruch und Wirklichkeit. 102. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft. Berlin, 23.-26.09.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04dogP 140

The electronic version of this article is the complete one and can be found online at:

Published: September 22, 2004

© 2004 Schütt et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.




Increased accumulation of lipofuscin (LF) in RPE cells occurs in various forms of macular degeneration. A2-E, a toxic and phototoxic major LF fluorophore, causes striking inhibition of catabolic lysosomal pathways. We now investigated possible A2-E metabolism and potential accumulation in different extralysosomal compartments of human RPE cells.


[14C]-Ethanolamine und Retinaldehyde were used as starting material for [14C]-A2-E synthesis. Human primary RPE cell cultures were loaded with [14C]-A2-E for four weeks. Cell viability was monitored using the MTT-assay, accumulation kinetics were analysed measuring the radioactivity in medium and cells. Incorporation of [14C]-A2-E into different cellular compartments was analysed using density gradient centrifugation.


Whereas cell viability remained stable within the control group, [14C]-A2-E treated cells showed a decrease of 10% viability in four weeks. [14C]-A2-E accumulated continuously and remained almost completely in the cells after termination of [14C]-A2-E incubation. Only 10% of [14C]-A2-E leaked into the medium corresponding to the fraction of died RPE cells. Gradient centrifugation showed at first a highly selective intralysosomal accumulation of [14C]-A2-E, followed by a slowly increasing incorporation into mitochondria.


A2-E can not be metabolised by lysosomal hydrolases and consequently accumulates age-dependend in the lysosomal compartment, where it causes lysosomal desintegration due to its detergent properties and is finally incorporated in the mitochondria, thereby possibly inducing apoptotic cell death. These results support the understanding of LF related toxicity in macular degenerations including ARMD and points to potential new treatment options.