Ut. Brunk et al., ACCUMULATION OF LIPOFUSCIN WITHIN RETINAL-PIGMENT EPITHELIAL-CELLS RESULTS IN ENHANCED SENSITIVITY TO PHOTOOXIDATION, Gerontology, 41, 1995, pp. 201-211
Retinal pigment epithelial (RPE) cells are largely postmitotic. They c
ontinuously phagocytose the outer tips of the photoreceptor outer segm
ents (POS). Over the life span of an individual, this activity results
, although surprisingly slowly, in the intralysomal accumulation of li
pofuscin, or age-pigment. Native lipofuscin shows orange-red autofluor
escence when exposed to blue light. The loss of energy resulting from
the conversion of excitatory blue light into emitted orange-red light
may induce photooxidative reactions. We exposed neonatal rabbit RPE ce
lls in culture to purified POS from cow eyes. The material were either
native or peroxidized by irradiation with UV-light before being added
to the RPE cultures. Lipofuscin accumulation was studied by transmiss
ion electron microscopy and measured by microfluorometric registration
of its autofluorescence. Cells exposed to peroxidized POS accumulated
much more lipofuscin than those exposed to native POS, indicating tha
t peroxidized outer segements are not digestable by lysosomal enzymes.
Furthermore, lipofuscin-loaded RPE cells were considerable more sensi
tive to visible blue light than unloaded control cells. The former one
s showed lysosomal membrane destabilization with ensuing leakage of ly
tic enzymes and eventually cell death. We suggest that photo-oxidation
of lysosomal membranes surrounding accumulated lipofuscin may be of i
mportance for the development of age-related macular degeneration.