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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

Synthesized A2E imaged with a confocal scanning laser ophthalmoscope (HRA2; Heidelberg Engineering, Heidelberg, Germany) using 488 nm (SW-AF) and 787 nm (NIR-AF) excitation. No signal was generated with the NIR excitation.
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Figure 8: Synthesized A2E imaged with a confocal scanning laser ophthalmoscope (HRA2; Heidelberg Engineering, Heidelberg, Germany) using 488 nm (SW-AF) and 787 nm (NIR-AF) excitation. No signal was generated with the NIR excitation.

Mentions: The observation that NIR-AF signals increase in parallel with increases in SW-AF at the border of GA may also not be fully understand. Hyperautofluorescence foci at the junctional zone of GA, at least in some cases, can be attributed to abnormally superimposed RPE cells [113, 114]. But whether this can account for more extensive bands of high NIR-AF [84] is not certain. It has been suggested that RPE lipofuscin may contribute to NIR-AF of the fundus [86]. However, albino rats do not exhibit NIR-AF despite the presence of lipofuscin [115] and as shown in Figure 8, we have not detected an NIR-AF signal from synthesized samples of A2E that otherwise emit fluorescence when excited at 488 nm. NIR-AF emission from other bisretinoids is unlikely, given the small structural differences amongst these compounds (Figure 2). If melanogenesis is the basis for increased NIR-AF brightness at the border of GA, as has been suggested [84, 105], one might expect that increased melanin concentrations would be visible as hyperpigmented spots and bands in color fundus photographs. In considering an optical effect as an explanation for increased NIR-AF signal it could be that RPE lipofuscin does not fluoresce in the NIR range but can modify the NIR-AF emission from melanin. This could occur if lipofuscin secondary lysosomes intercalate amongst apically situated melanosomes [78, 116] thereby reducing the NIR-AF quenching associated with secondary self-absorbance of the fluorescence emission. A mechanism such as this might also explain why hyperautofluorescent rings visible in the NIR-AF fundus images in retinitis pigmentosa exhibit spatial correspondence with high intensity rings observed in SW-AF images [117].


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

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

Synthesized A2E imaged with a confocal scanning laser ophthalmoscope (HRA2; Heidelberg Engineering, Heidelberg, Germany) using 488 nm (SW-AF) and 787 nm (NIR-AF) excitation. No signal was generated with the NIR excitation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 8: Synthesized A2E imaged with a confocal scanning laser ophthalmoscope (HRA2; Heidelberg Engineering, Heidelberg, Germany) using 488 nm (SW-AF) and 787 nm (NIR-AF) excitation. No signal was generated with the NIR excitation.
Mentions: The observation that NIR-AF signals increase in parallel with increases in SW-AF at the border of GA may also not be fully understand. Hyperautofluorescence foci at the junctional zone of GA, at least in some cases, can be attributed to abnormally superimposed RPE cells [113, 114]. But whether this can account for more extensive bands of high NIR-AF [84] is not certain. It has been suggested that RPE lipofuscin may contribute to NIR-AF of the fundus [86]. However, albino rats do not exhibit NIR-AF despite the presence of lipofuscin [115] and as shown in Figure 8, we have not detected an NIR-AF signal from synthesized samples of A2E that otherwise emit fluorescence when excited at 488 nm. NIR-AF emission from other bisretinoids is unlikely, given the small structural differences amongst these compounds (Figure 2). If melanogenesis is the basis for increased NIR-AF brightness at the border of GA, as has been suggested [84, 105], one might expect that increased melanin concentrations would be visible as hyperpigmented spots and bands in color fundus photographs. In considering an optical effect as an explanation for increased NIR-AF signal it could be that RPE lipofuscin does not fluoresce in the NIR range but can modify the NIR-AF emission from melanin. This could occur if lipofuscin secondary lysosomes intercalate amongst apically situated melanosomes [78, 116] thereby reducing the NIR-AF quenching associated with secondary self-absorbance of the fluorescence emission. A mechanism such as this might also explain why hyperautofluorescent rings visible in the NIR-AF fundus images in retinitis pigmentosa exhibit spatial correspondence with high intensity rings observed in SW-AF images [117].

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