Drusen-associated
Retinal Degeneration
Drusen--variably sized extracellular deposits that form between the
retinal pigmented epithelium (RPE) and Bruchs membrane--are commonly
found in aged eyes. However, numerous and/or confluent drusen are a
significant risk factor for age-related macular degeneration (AMD).
Researchers at the University of California"s Center for the Study of
Macular Degeneration and Department of Molecular, Cellular and Developmental
Biology aimed to investigate the impact of drusen on overlying cells
of the retina, and found that the retinal cells of both types of drusen
exhibit structural and molecular abnormalities indicative of photoreceptor
degeneration and Müller glial activation. These abnormalities resemble
the degenerative effects common to many forms of retinal degeneration,
but are confined to areas directly overlying drusen. The results suggest
that photoreceptor cell function is compromised as a consequence of
drusen formation.
In the study, researchers dissected tissue containing retina and RPE/choroid
from human donor eyes, embedded it in agarose, and sectioned it at 100
µm using a vibratome. They immunostained sections with a panel
of antibodies that labeled glial cells as well as first-, second- and
third-order retinal neurons, and they processed for confocal microscopy.
Retinal cells overlying both soft and hard drusen exhibited numerous
structural and molecular abnormalities. Rod opsin immunolabeling, normally
detectable only in the outer segments of rod photoreceptors, was also
observed in the inner segment, cell body, axon and axon terminal of
photoreceptors that overlie drusen. Labeling with this antibody also
revealed the deflection and shortening of rod inner and outer segments.
Cone photoreceptors displayed similar structural abnormalities, as well
as a decrease in cone opsin immunoreactivity. Results also showed drusen-associated
abnormalities in the synaptic terminals of photoreceptor cells. In addition,
they observed an increase in intermediate filament protein immunoreactivity
(vimentin and glial fibrillary acidic protein) within Müller glial
cells in areas of retina overlying drusen. Both soft and hard drusen
were associated with a similar spectrum of effects in macular and extramacular
regions alike. Second- and third-order neurons, including bipolar, horizontal,
amacrine and ganglion cells, all appeared unaffected. The structural
and molecular abnormalities observed in photoreceptors and Müller
glial cells were confined to retinal regions directly overlying and
immediately adjacent to drusen; more distant retinal regions appeared
unperturbed. Remarkably, significant abnormalities were observed over
small subclinical drusen.
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