Back to Search
Start Over
Proteomic and phototoxic characterization of melanolipofuscin: correlation to disease and model for its origin.
- Source :
-
Molecular vision [Mol Vis] 2007 Mar 01; Vol. 13, pp. 318-29. Date of Electronic Publication: 2007 Mar 01. - Publication Year :
- 2007
-
Abstract
- Purpose: Melanolipofuscin (MLF) is a complex granule, exhibiting properties of both melanosomes and lipofuscin (LF) granules, which accumulates in retinal pigment epithelial (RPE) cells and may contribute to the etiology of age-related macular degeneration (AMD). MLF accumulation has been reported by Feeney-Burns to more closely reflect the onset of AMD than the accumulation of lipofuscin. In an effort to assess the possible contribution MLF may have to the onset of AMD, we analyzed the phototoxicity and protein composition of MLF and compared those results to that of LF.<br />Methods: Specifically, we observed the accumulation of MLF in human RPE from different decades of life, and assessed the phototoxicity of these granules. We also employed fluorescence spectroscopy, atomic force microscopy, transmission and scanning electron microscopy and proteomic analysis to examine the composition of MLF granules in an effort to ascertain their origin.<br />Results: Our results show that MLF granules are phototoxic and their accumulation more closely reflects the onset of AMD than does LF accumulation. Our compositional analysis of MLF has shown that while these granules contain some similarities to LF granules, MLF is substantially different. Of significant interest is the finding that MLF, in contrast to LF, does not contain photoreceptor-specific proteins, suggesting that MLF may not originate from the phagocytosis of photoreceptor outer segments. Instead the presence of RPE- and melanosome-specific proteins would suggest that MLF accumulates as a result of the melanosomal autophagocytosis of RPE cells.<br />Conclusions: Our results provide significant insight into understanding the formation and toxicity of MLF and suggest a possible contribution to the etiology of retinal diseases.
- Subjects :
- Adult
Aged
Cytoplasmic Granules ultrastructure
Humans
Immunoblotting
Lipofuscin metabolism
Melanosomes ultrastructure
Photoreceptor Cells metabolism
Pigment Epithelium of Eye cytology
Pigment Epithelium of Eye metabolism
Proteome isolation & purification
Rhodopsin metabolism
Spectrometry, Fluorescence
Lipofuscin toxicity
Macular Degeneration pathology
Melanosomes metabolism
Models, Biological
Proteomics
Subjects
Details
- Language :
- English
- ISSN :
- 1090-0535
- Volume :
- 13
- Database :
- MEDLINE
- Journal :
- Molecular vision
- Publication Type :
- Academic Journal
- Accession number :
- 17392682