Aktuelle Tagungsinformationen
News and Updates
Anmeldung zur Tagung
Registration
Hotelbuchung
Hotel Registration
Grußwort
Welcome address
Beteiligte Gesellschaften
Societies involved
Eröffnung des Kongresses
Opening Ceremony
Preise
Awards
Wissenschaftliches Programm
Scientific program
Posterpräsentationen
Poster Presentation
Kurse
Courses
Begleitende Veranstaltungen
Collateral Events
Rahmenprogramm
Social program
Jubiläumsparty
Jubilee Party
DOG Information
DOG Information
Allgemeine Informationen
General Information
Autorenindex
Index of Authors
Ausstellerliste
Exhibitors
Sponsoren
Sponsors
Teilnahmegebühren
Registration fees
Impressum
DOG Homepage
A2-E, a Retinoid Compound of Lipofuscin, Inhibits Phagocytosis and Autophagy in Human RPE Cells
1Schütt F., 2Kopietz J., 1Holz F. G.,
1Ruprecht-Karls-Universität Heidelberg, Universitäts-Augenklinik (Heidelberg)
2Ruprecht-Karls-Universität Heidelberg, Abteilung für Pathochemie und Neurochemie (Heidelberg)
Purpose: Age-related macular degeneration is associated with accumulation of intracellular (lipofuscin) and extracellular biomolecules. Inhibition of phagocytosis and autophagy by toxic components of lipofuscin with consectutive deterioration of the degradative metablosim may represent contributary factors. Herein we sought to evaluate the effect of A2-E on the phagocytic and autophagocytic capacity of cultured human RPE-cells.
Method: Rod outer segments (ROS) were isolated from pig eyes, radiolabeled using the Iodobead method and included in the culture medium of A2-E-loaded and control human RPE cells. Phagocytosis rates were calculated from the disappearance of radioactivity from the medium. Intracellular accumulation (storage) of phagocytosed material was determined by measurement of intracellular radioactivity. Autophagy was measured in pulse-chase experiments using 3[H]-leucine labeled and A2-E fed cell cultures in absence and presence of the lysosomal inhibitor 3-methyl-adenine (10mM).
Results: Within 24 hours 40% of ROS were ingested and degraded completely by controls. A2-E fed cells showed only 14% phagocytosis and 5% intracellular degradation. Autophagy was reduced significantly.
Conclusions: Phagocytic capacity of human RPE cells is impaired by A2-E, a major fluorophore of lipofuscin. Such mechanism may be operative in macular/retinal degenerations associated with excessive lipofuscin accumulations, and may explain recent in vivo observations indicating impaired sensitivity of apposing photoreceptors over areas with markedly elevated fundus autofluorescence due to RPE-lipofuscin storage.