Compositional studies of human RPE lipofuscin
L S Murdaugh1, L B Avalle, S Mandal
1Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL, USA.
Journal of Mass Spectrometry : JMS
|September 23, 2010
Summary
Age-related macular degeneration (AMD) involves lipofuscin accumulation, particularly A2E-like compounds, leading to photoreceptor cell death. These hydrophobic A2E derivatives form higher molecular weight products, driving AMD progression.
Area of Science:
- Ophthalmology
- Biochemistry
- Cell Biology
Background:
- Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly.
- Lipofuscin accumulation in retinal pigment epithelium (RPE) precedes photoreceptor cell death in AMD.
- A2E, a bis-retinoid pyridinium compound, is a major photosensitive component of RPE lipofuscin.
Purpose of the Study:
- To characterize the photosensitive components of RPE lipofuscin.
- To investigate the formation and properties of A2E and related compounds in AMD.
Main Methods:
- Mass spectrometry was used to characterize A2E and related chromophores.
- Lipofuscin extracts from human donors were analyzed.
- In vitro self-reaction experiments were conducted to study compound formation.
Main Results:
- A2E has a mass of 592 Da; related chromophores show fragmentation losses of M ± 190, 174, and/or 150 Da.
- RPE lipofuscin contains up to 15 hydrophobic A2E-like components, forming higher molecular weight products (800-900, 970-1080, >1200 m/z).
- These higher molecular weight species result from A2E oxidation product self-reactions or reactions with A2E, increasing hydrophobicity.
Conclusions:
- A2E and its hydrophobic derivatives are key contributors to RPE lipofuscin.
- The formation of higher molecular weight, more hydrophobic A2E derivatives drives their sequestration into granules.
- This sequestration may reduce A2E reactivity in vivo, but the overall process contributes to AMD pathogenesis.
