Age, lipofuscin and melanin oxidation affect fundus near-infrared autofluorescence

Taubitz, Tatjana; Fang, Yuan; Biesemeier, Antje; Julien-Schraermeyer, Sylvie; Schraermeyer, Ulrich

doi:10.1016/j.ebiom.2019.09.048

Cited by 42 publications

(38 citation statements)

References 43 publications

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“…66,67 Previously, we have suggested that the NIR-AF emitted by lipofuscin granules and the lipofuscin moiety of melanolipofuscin granules may be mainly due to the accumulation of melanin degradation products. 68 Bisretinoids contained in lipofuscin granules in degenerating RPE cells can also undergo photo-oxidation leading to additional toxic products. These oxidized and fragmented bisretinoids might contribute to NIR-AF as well.…”

Section: Discussionmentioning

confidence: 99%

“…We further demonstrated that these granules were lipofuscin and melanolipofuscin formed by the fusion of lipofuscin and melanin with aging and oxidative stress . Previously, we have suggested that the NIR‐AF emitted by lipofuscin granules and the lipofuscin moiety of melanolipofuscin granules may be mainly due to the accumulation of melanin degradation products . Bisretinoids contained in lipofuscin granules in degenerating RPE cells can also undergo photo‐oxidation leading to additional toxic products.…”

Section: Discussionmentioning

confidence: 99%

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Fundus autofluorescence, spectral‐domain optical coherence tomography, and histology correlations in a Stargardt disease mouse model

et al. 2020

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Stargardt disease (STGD1), known as inherited retinal dystrophy, is caused by ABCA4 mutations. The pigmented Abca4−/− mouse strain only reflects the early stage of STGD1 since it is devoid of retinal degeneration. This blue light‐illuminated pigmented Abca4−/− mouse model presented retinal pigment epithelium (RPE) and photoreceptor degeneration which was similar to the advanced STGD1 phenotype. In contrast, wild‐type mice showed no RPE degeneration after blue light illumination. In Abca4−/− mice, the acute blue light diminished the mean autofluorescence (AF) intensity in both fundus short‐wavelength autofluorescence (SW‐AF) and near‐infrared autofluorescence (NIR‐AF) modalities correlating with reduced levels of bisretinoid‐fluorophores. Blue light‐induced RPE cellular damage preceded the photoreceptors loss. In late‐stage STGD1‐like patient and blue light‐illuminated Abca4−/− mice, lipofuscin and melanolipofuscin granules were found to contribute to NIR‐AF, indicated by the colocalization of lipofuscin‐AF and NIR‐AF under the fluorescence microscope. In this mouse model, the correlation between in vivo and ex vivo assessments revealed histological characteristics of fundus AF abnormalities. The flecks which are hyper AF in both SW‐AF and NIR‐AF corresponded to the subretinal macrophages fully packed with pigment granules (lipofuscin, melanin, and melanolipofuscin). This mouse model, which has the phenotype of advanced STGD1, is important to understand the histopathology of Stargardt disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fundus autofluorescence, spectral‐domain optical coherence tomography, and histology correlations in a Stargardt disease mouse model

et al. 2020

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“…granules exhibit both SWAF and IRAF in aged human donor eyes 24 . This finding helps explain our previously published report showing co-localization of SWAF and IRAF signals in AOSLO 9 .…”

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confidence: 94%

Microstructure of the retinal pigment epithelium near-infrared autofluorescence in healthy young eyes and in patients with AMD

Vienola

Zhang

Snyder

et al. 2020

Sci Rep

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Retinal pigmented epithelial (RPE) cells are essential for maintaining normal visual function, especially in their role in the visual cycle, and are thought to be one of the first cell classes affected by age-related macular degeneration (AMD). Clinical imaging systems routinely evaluate the structure of the RPE at the tissue level, but cellular level information may provide valuable RPE biomarkers of health, aging and disease. In this exploratory study, participants were imaged with 795 nm excitation in adaptive optics scanning laser ophthalmoscopy (AOSLO) to observe the microstructure of the near-infrared autofluorescence (AO-IRAF) from the RPE layer in healthy retinas and patients with AMD. The expected hexagonal mosaic of RPE cells was only sometimes seen in normal eyes, while AMD patients exhibited highly variable patterns of altered AO-IRAF. In some participants, AO-IRAF structure corresponding to cones was observed, as we have demonstrated previously. In some AMD patients, marked alterations in the pattern of AO-IRAF could be seen even in areas where the RPE appeared relatively normal in clinical imaging modalities, such as spectral domain optical coherence tomography (SD-OCT). AO-IRAF imaging using AOSLO offers promise for better detection and understanding of early RPE changes in the course of AMD, potentially before clinical signs appear. The human retina naturally emits light as it is absorbing light due to its intrinsic autofluorescence (AF). Over the past three decades, several imaging modalities, such as the scanning laser ophthalmoscope (SLO), have been utilized to visualize the AF of the retina 1-4. Clinically, fundus autofluorescence (FAF) has become routine for evaluating disease status and monitoring progression in certain pathologies because of its potential to reveal retinal pigment epithelium alterations that are difficult to distinguish using other imaging modalities 4-6. It has also been capitalized on in adaptive optics scanning laser ophthalmoscopy (AOSLO) to image individual retinal pigmented epithelial (RPE) cells 7-9. However, many questions remain about the origin of retinal AF and its usefulness for visualizing the RPE cell mosaic in aging and in diseases of the outer retina, such as age-related macular degeneration (AMD). Fundus AF originates from the retinal pigment epithelium and choroid. Though choroidal AF is thought to arise primarily from melanosomes and melanocytes, RPE cells contain additional AF organelles, including lipofuscin, and melanolipofuscin (complex aggregates of melanin and lipofuscin) 10. Fundus autofluorescence has been evaluated at several imaging wavelengths across the visible spectrum and into the near-infrared (NIR). When using short wavelength autofluorescence (SWAF) excitation (i.e. visible wavelengths shorter than 700 nm), the AF signal has been thought to originate primarily from lipofuscin. Lipofuscin is a complex aggregate of bisretinoids, some of which are autofluorescent, that accumulates in RPE cells over the lifetime 11,12 because of the visual cy...

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“…Boulton and colleagues identified RPE lipofuscin as a fraction at the interface between 1.2 and 1.4 M of sucrose [21,22]. Similar fractionation methods have been adopted by other investigators to isolate RPE lipofuscin granules for lipofuscin studies, including morphological, lipid, proteomic, and melanin oxidation analyses [23][24][25][26]. The lipofuscin fraction was originally identified by fluorescence microscopy.…”

Section: Introductionmentioning

confidence: 99%

A2E Distribution in RPE Granules in Human Eyes

Guan

Jiao

et al. 2020

Molecules

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A2E (N-retinylidene-N-retinylethanolamine) is a major fluorophore in the RPE (retinal pigment epithelium). To identify and characterize A2E-rich RPE lipofuscin, we fractionated RPE granules from human donor eyes into five fractions (F1–F5 in ascending order of density) by discontinuous sucrose density gradient centrifugation. The dry weight of each fraction was measured and A2E was quantified by liquid chromatography/mass spectrometry (LC/MS) using a synthetic A2E homolog as a standard. Autofluorescence emission was characterized by a customer-built spectro-fluorometer system. A significant A2E level was detected in every fraction, and the highest level was found in F1, a low-density fraction that makes up half of the total weight of all RPE granules, contains 67% of all A2E, and emits 75% of projected autofluorescence by all RPE granules. This group of RPE granules, not described previously, is therefore the most abundant RPE lipofuscin granule population. A progressive decrease in autofluorescence was observed from F2 to F4, whereas no autofluorescence emission was detected from the heavily pigmented F5. The identification of a novel and major RPE lipofuscin population could have significant implications in our understanding of A2E and lipofuscin in human RPE.

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Age, lipofuscin and melanin oxidation affect fundus near-infrared autofluorescence

Cited by 42 publications

References 43 publications

Fundus autofluorescence, spectral‐domain optical coherence tomography, and histology correlations in a Stargardt disease mouse model

Fundus autofluorescence, spectral‐domain optical coherence tomography, and histology correlations in a Stargardt disease mouse model

Microstructure of the retinal pigment epithelium near-infrared autofluorescence in healthy young eyes and in patients with AMD

A2E Distribution in RPE Granules in Human Eyes

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