Lack of correlation between the spatial distribution of A2E and lipofuscin fluorescence in the human retinal pigment epithelium

The accumulation of lipofuscin in the RPE is a hallmark of aging in the eye. The best characterized component of lipofuscin is A2E, a bis-retinoid byproduct of the normal retinoid visual cycle, which exhibits a broad spectrum of cytotoxic effects in vitro. The purpose of our study was to correlate t...

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Veröffentlicht in:Investigative ophthalmology & visual science 2013-08, Vol.54 (8), p.5535-5542
Hauptverfasser: Ablonczy, Zsolt, Higbee, Daniel, Anderson, David M, Dahrouj, Mohammad, Grey, Angus C, Gutierrez, Danielle, Koutalos, Yiannis, Schey, Kevin L, Hanneken, Anne, Crouch, Rosalie K
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Sprache:eng
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Zusammenfassung:The accumulation of lipofuscin in the RPE is a hallmark of aging in the eye. The best characterized component of lipofuscin is A2E, a bis-retinoid byproduct of the normal retinoid visual cycle, which exhibits a broad spectrum of cytotoxic effects in vitro. The purpose of our study was to correlate the distribution of lipofuscin and A2E across the human RPE. Lipofuscin fluorescence was imaged in flat-mounted RPE from human donors of various ages. The spatial distributions of A2E and its oxides were determined using matrix-assisted laser desorption-ionization imaging mass spectrometry (MALDI-IMS) on flat-mounted RPE tissue sections and retinal cross-sections. Our data support the clinical observations of strong RPE fluorescence, increasing with age, in the central area of the RPE. However, there was no correlation between the distribution of A2E and lipofuscin, as the levels of A2E were highest in the far periphery and decreased toward the central region. High-resolution MALDI-IMS of retinal cross-sections confirmed the A2E localization data obtained in RPE flat-mounts. Singly- and doubly-oxidized A2E had distributions similar to A2E, but represented
ISSN:1552-5783
0146-0404
1552-5783
DOI:10.1167/iovs.13-12250