Abstract
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.
Highlights
The age pigment lipofuscin accumulates within the lysosomal system of a variety of postmitotic cells throughout life and is considered to be a biomarker of cell aging
We have found that illumination of lipofuscin with visible light is capable of extragranular lipid peroxidation, enzyme inactivation, and protein oxidation
To allow for interexperimental variations due to enzyme and lipofuscin, batch enzyme activity is expressed as a decrease relative to time 0 rather than an absolute value
Summary
The age pigment lipofuscin accumulates within the lysosomal system of a variety of postmitotic cells throughout life and is considered to be a biomarker of cell aging. Ocular lipofuscin may have a unique role to play in aging of the RPE, a tissue that is continually exposed to visible light (400 –700 nm) and high oxygen tensions (ϳ70 mm Hg) Studies have shown this type of lipofuscin to be a photoinducible generator of superoxide ions, singlet oxygen, hydrogen peroxide, and lipid peroxides (6 –9), all of which are reactive oxygen species implicated in general aging processes. These species can adversely affect cell function by damaging proteins, carbohydrates, DNA, and lipids [10]. We have confirmed that lipofuscin granules incubated with visible light induce lipid peroxidation and cause enzyme inactivation supporting our hypothesis that lipofuscin contributes to aging of the RPE and is a risk factor for age-related macular degeneration
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
