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Fundus Autofluorescence and RPE Lipofuscin in Age-Related Macular Degeneration.

Sparrow JR, Duncker T - J Clin Med (2014)

Bottom Line: SW-AF imaging is currently used in the clinical management of retinal disorders and the advantages of NIR-AF are increasingly recognized.Here we visit the damaging properties of RPE lipofuscin that could be significant when expressed on a background of genetic susceptibility.To advance interpretations of disease-related patterns of fundus AF in AMD, we also consider the photochemical and spectrophotometric features of the lipofuscin compounds responsible for generating the fluorescence emission.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Ophthalmology, Columbia University Medical Center, 635 W. 165th Street, New York, NY 10032, USA ; Department of Pathology and Cell Biology, Columbia University Medical Center, 630 168th Street, New York, NY 10032, USA.

ABSTRACT
Genes that increase susceptibility to age-related macular degeneration (AMD) have been identified; however, since many individuals carrying these risk alleles do not develop disease, other contributors are involved. One additional factor, long implicated in the pathogenesis of AMD, is the lipofuscin of retinal pigment epithelium (RPE). The fluorophores that constitute RPE lipofuscin also serve as a source of autofluorescence (AF) that can be imaged by confocal laser ophthalmoscopy. The AF originating from lipofuscin is excited by the delivery of short wavelength (SW) light. A second autofluorescence is emitted from the melanin of RPE (and choroid) upon near-infrared (NIR-AF) excitation. SW-AF imaging is currently used in the clinical management of retinal disorders and the advantages of NIR-AF are increasingly recognized. Here we visit the damaging properties of RPE lipofuscin that could be significant when expressed on a background of genetic susceptibility. To advance interpretations of disease-related patterns of fundus AF in AMD, we also consider the photochemical and spectrophotometric features of the lipofuscin compounds responsible for generating the fluorescence emission.

No MeSH data available.


Related in: MedlinePlus

Fluorescence emission spectra of human RPE lipofuscin and A2E (in PBS with 2% DMSO). Emission was recorded at excitation wavelengths 436, 480 and 545 nm as published [49]. Emission maxima are indicated.
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Figure 3: Fluorescence emission spectra of human RPE lipofuscin and A2E (in PBS with 2% DMSO). Emission was recorded at excitation wavelengths 436, 480 and 545 nm as published [49]. Emission maxima are indicated.

Mentions: In clinical settings, SW-fundus AF is excited by wavelengths ranging from 488 nm, the excitation employed with a confocal scanning laser ophthalmoscope (cSLO), to the 535–580 nm range utilized by a modified fundus camera [46] and the 568 nm light used with fluorescence adaptive optics ophthalmoscopy [17, 47, 48]. Fundus autofluorescence measured in vivo by spectrophotometry has a broad excitation spectrum that peaks between 490–510 nm. The fluorescence emission is also broad and centered at approximately 600 nm [11, 17]. RPE lipofuscin ex vivo exhibits an excitation spectrum that peaks between 450–490 nm; the fluorescence emission is maximal at ~600 nm [49] (Figure 3). Moreover, just as with fundus autofluorescence, the emission spectrum recorded from whole lipofuscin exhibits red-shifts when excited by progressively longer wavelengths [49] (Figure 3). Thus the spectral characteristics of fundus autofluorescence are consistent with that of RPE lipofuscin [43, 50–52] and chiefly with an origin from the bisretinoid fluorescent pigments that are known constituents of RPE lipofuscin. The bisretinoids that have been characterized have absorbance maxima varying from 440 nm to 510 nm and they emit with an orange fluorescence that peaks at ~600 nm [26]. The bisretinoid A2E can emit fluorescence at longer wavelength excitations such as 545 nm (Figure 3B).


Fundus Autofluorescence and RPE Lipofuscin in Age-Related Macular Degeneration.

Sparrow JR, Duncker T - J Clin Med (2014)

Fluorescence emission spectra of human RPE lipofuscin and A2E (in PBS with 2% DMSO). Emission was recorded at excitation wavelengths 436, 480 and 545 nm as published [49]. Emission maxima are indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358814&req=5

Figure 3: Fluorescence emission spectra of human RPE lipofuscin and A2E (in PBS with 2% DMSO). Emission was recorded at excitation wavelengths 436, 480 and 545 nm as published [49]. Emission maxima are indicated.
Mentions: In clinical settings, SW-fundus AF is excited by wavelengths ranging from 488 nm, the excitation employed with a confocal scanning laser ophthalmoscope (cSLO), to the 535–580 nm range utilized by a modified fundus camera [46] and the 568 nm light used with fluorescence adaptive optics ophthalmoscopy [17, 47, 48]. Fundus autofluorescence measured in vivo by spectrophotometry has a broad excitation spectrum that peaks between 490–510 nm. The fluorescence emission is also broad and centered at approximately 600 nm [11, 17]. RPE lipofuscin ex vivo exhibits an excitation spectrum that peaks between 450–490 nm; the fluorescence emission is maximal at ~600 nm [49] (Figure 3). Moreover, just as with fundus autofluorescence, the emission spectrum recorded from whole lipofuscin exhibits red-shifts when excited by progressively longer wavelengths [49] (Figure 3). Thus the spectral characteristics of fundus autofluorescence are consistent with that of RPE lipofuscin [43, 50–52] and chiefly with an origin from the bisretinoid fluorescent pigments that are known constituents of RPE lipofuscin. The bisretinoids that have been characterized have absorbance maxima varying from 440 nm to 510 nm and they emit with an orange fluorescence that peaks at ~600 nm [26]. The bisretinoid A2E can emit fluorescence at longer wavelength excitations such as 545 nm (Figure 3B).

Bottom Line: SW-AF imaging is currently used in the clinical management of retinal disorders and the advantages of NIR-AF are increasingly recognized.Here we visit the damaging properties of RPE lipofuscin that could be significant when expressed on a background of genetic susceptibility.To advance interpretations of disease-related patterns of fundus AF in AMD, we also consider the photochemical and spectrophotometric features of the lipofuscin compounds responsible for generating the fluorescence emission.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Ophthalmology, Columbia University Medical Center, 635 W. 165th Street, New York, NY 10032, USA ; Department of Pathology and Cell Biology, Columbia University Medical Center, 630 168th Street, New York, NY 10032, USA.

ABSTRACT
Genes that increase susceptibility to age-related macular degeneration (AMD) have been identified; however, since many individuals carrying these risk alleles do not develop disease, other contributors are involved. One additional factor, long implicated in the pathogenesis of AMD, is the lipofuscin of retinal pigment epithelium (RPE). The fluorophores that constitute RPE lipofuscin also serve as a source of autofluorescence (AF) that can be imaged by confocal laser ophthalmoscopy. The AF originating from lipofuscin is excited by the delivery of short wavelength (SW) light. A second autofluorescence is emitted from the melanin of RPE (and choroid) upon near-infrared (NIR-AF) excitation. SW-AF imaging is currently used in the clinical management of retinal disorders and the advantages of NIR-AF are increasingly recognized. Here we visit the damaging properties of RPE lipofuscin that could be significant when expressed on a background of genetic susceptibility. To advance interpretations of disease-related patterns of fundus AF in AMD, we also consider the photochemical and spectrophotometric features of the lipofuscin compounds responsible for generating the fluorescence emission.

No MeSH data available.


Related in: MedlinePlus