gms | German Medical Science

102. Jahrestagung der DOG

Deutsche Ophthalmologische Gesellschaft e. V.

23. bis 26.09.2004, Berlin

Pathogenetic key factors in RPE: new findings by using new "methodical tools"

Meeting Abstract

  • corresponding author J. Kopitz - Molekulare Pathologie, Universität Heidelberg
  • F. Schütt - Universitäts-Augenklinik Heidelberg
  • M. Bergmann - Molekulare Pathologie, Universität Heidelberg
  • E. Kämmerer - Molekulare Pathologie, Universität Heidelberg
  • A. Bindewald - Universitäts-Augenklinik Bonn
  • T.U. Krohne - Universitäts-Augenklinik Bonn
  • F.G. Holz - Universitäts-Augenklinik Bonn

Evidenzbasierte Medizin - Anspruch und Wirklichkeit. 102. Jahrestagung der Deutschen Ophthalmologischen Gesellschaft. Berlin, 23.-26.09.2004. Düsseldorf, Köln: German Medical Science; 2004. Doc04dogSA.07.02

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Veröffentlicht: 22. September 2004

© 2004 Kopitz et al.
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Lipofuscin accumulation in postmitotic retinal pigment epithelium (RPE) is a hallmark of aging and various degenerative and inherited retinal disorders. Although excessive accumulation of lipofuscin in the RPE is considered an essential pathogenic factor during the development of AMD, individual lipofuscin compounds and consequently also the molecular mechanisms of their pathogenic action are poorly characterized. We consider a profound biochemical characterization of lipofuscin compounds and the subsequent elucidation of their potential RPE-damaging actions as a key to comprehension of the pathogenesis of AMD and related disorders.

Lipofuscin consists mainly of proteinous compounds and lipids. Methods of proteome analysis, like 2-D gelelectrophoresis, 2D-HPLC an mass spectrometric analyses, are used to characterize the protein compounds. Posttranslational modifications/damages are analysed with immunological methods and by mass spectrometry. The bases of lipid analysis are specific extraction procedures, chromatographic purification and specialized mass spectrometric methods. The subsequent investigations on the cellular action of individual identified lipofuscin compounds are conducted using human RPE cell cultures that are established from donor eyes.

Examples of an succesful application of such strategy are our investigations on the induction of lysosomal dysfunction with resulting RPE-damage by the lipid compound A2-E [1], [2], [3], [4], [5], [6]. Analysis of the proteinous fraction of lipofuscin revealed, that oxidatively damaged proteins preferentially accumulate in lipofuscin. Recent investigations using cultured RPE cells and isolated lysosomes suggested that these altered protein structures contribute to lipofuscinogenesis and RPE damage [7], [8], [9], [10].

Such investigations applying the above mentioned "new methological tools" for the identification of pathogenic key factors in RPE are likely to put on the basis for the development of new therapeutic strategies for retinal degeneration that are associated with excessive lipofuscin accumulation.


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