Anmeldung zur Tagung
Registration
Grußwort
Invitation
Themen
Topics
Allgemeiner Ablauf
General overview
Wissenschaftliches Programm
Scientific program
Kurse
Courses
Symposien
Symposiums
Frühstück mit Spezialisten
Breakfast with specialists
Arzthelferinnen-Fortbildung
Rahmenprogramm
Social program
DOG Information
DOG Information
Allgemeine Informationen
General Information
Autorenindex
Index of Authors
Ausstellerliste
Exhibitors
Sponsoren
Sponsors
Teilnahmegebühren
Registration fees
Impressum
The lipofuscin fluorophor A2-E desintegrates various membranes in retinal pigment epithelial cells
1Schütt F., 2Bergmann M., 2Kopitz J., 1Holz F. G.
1Dept. of Ophthalmology; 2Dept. of Pathobiochemistry and Neurochemistry, INF 400 and 220/221, University of Heidelberg, Heidelberg; Germany
Objective: Increased accumulation of lipofuscin (LF) in RPE cells
occurs in various forms of macular degeneration. A2E, a major LF fluorophore,
causes striking inhibition of catabolic lysosomal pathways. Its structure
suggests that it may exert additional pathogenetic effects as a detergent
on cellular membranes. Although the lysomoal membrane would be the primary
target, rupture and leakage could affect other membranes. We investigated
differential detergent effects on various cellular membranes.
Methods: Cultured human RPE-cells were disrupted by nitrogen cavitation,
and a postnuclear supernatant (PNS) was prepared by centrifugation. The
PNS was fractionated by ultracentrifugation in order to isolate lysosomes,
microsomes, mitochondria and Golgi/ER membranes. To investigate a possible
detergent effect of A2-E on these membranes, latency assays were conducted.
Results: Following membrane damaging concentrations of A2-E were
determined: Mitochondria 1-2 µM, lysosomes 2 µM, Golgi/ER
10 µM, plasma membranes 100 µM.
Discussion: Desintegration of various cellular membranes occurs
at a wide range of A2E concentrations indicating different susceptibilities.
After initial accumulation in the lysosomal compartment follows membrane
damage and release of toxic hydrolases which also start the apototic cascade.
A2-E reaches the mitochondrial membranes leading to mitochondrial dysfunction
with decreased ATP levels and induction of apoptosis. It is unlikely that
by A2E leakage from the lysosomal compartment cytoplasmic concentrations
are reached sufficient for damage of ER/Golgi membranes or the plasma
membrane.
Support: DFG grant Ho 1926/2-1, DFG Priority Program AMD (1088), State
of Baden-Wuerttemberg Research Fund 500/2000