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J Biol Chem, Vol. 274, Issue 34, 23828-23832, August 20, 1999
From the University Department of Ophthalmology, Manchester Royal
Eye Hospital, Manchester M13 9WH, United Kingdom and the
The presence of the age pigment lipofuscin is
associated with numerous age-related diseases. In the retina lipofuscin
is located within the pigment epithelium where it is exposed to high
oxygen and visible light, a prime environment for the generation of
reactive oxygen species. Although we, and others, have demonstrated
that retinal lipofuscin is a photoinducible generator of reactive
oxygen species it is unclear how this may translate into cell damage. The position of lipofuscin within the lysosome infers that irradiated lipofuscin is liable to cause oxidative damage to either the lysosomal membrane or the lysosomal enzymes. We have found that illumination of
lipofuscin with visible light is capable of extragranular lipid peroxidation, enzyme inactivation, and protein oxidation. These effects, which were pH-dependent, were significantly
reduced by the addition of the antioxidants, superoxide dismutase and
1,4-diazabicyclo(2,2,2)-octane, confirming a role for both the
superoxide anion and singlet oxygen. We postulate that lipofuscin may
compromise retinal cell function by causing loss of lysosomal integrity
and that this may be a major contributory factor to the pathology
associated with retinal light damage and diseases such as age-related
macular degeneration.
Cell and Molecular Biology Unit, Department of Optometry
and Vision Sciences, Cardiff University, Cardiff CF1 3XF, United
Kingdom
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