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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

A2E photobleaching by irradiation at 480 nm for 4 and 8 min. Fluorescence intensity decreases with irradiation and the emission maximum undergoes a hypsochromic shift. Emission peak wavelengths (nm) are indicated adjacent to each trace.
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Figure 4: A2E photobleaching by irradiation at 480 nm for 4 and 8 min. Fluorescence intensity decreases with irradiation and the emission maximum undergoes a hypsochromic shift. Emission peak wavelengths (nm) are indicated adjacent to each trace.

Mentions: The propensity for bisretinoids to undergo photooxidative and photodegradative processes may underlie the decline in RPE lipofuscin fluorescence emission (photobleaching) that has been observed in non-human primates during in vivo fluorescence imaging by adaptive optics scanning laser ophthalmoscopy [48, 71], with cell culture models [72] and in non-cellular assays (Figure 4). Lipofuscin photobleaching may also explain why after surgical repair of some cases of retinal detachment, hyperautofluorescent lines coursing parallel to retinal blood vessels can be visible in fundus AF images [73, 74] (Figure 5). The hyperautofluorescent imprint has been interpreted as indicating a change in the position of the vessel relative to the underlying retinal tissue and is visible because of contrasting levels of AF brightness. At any given time, the intensity of fundus AF is likely the difference between fluorophore synthesis on the one hand, and lipofuscin photoxidation/photodegradation in RPE, on the other. Under the shadow of a blood vessel, the formation of bisretinoid from retinaldehyde (with 11-cis being converted to all-trans-retinal) would likely continue unabated [20, 30, 75–77] but lipofuscin photooxidation and photobleaching would be substantially reduced. As a result, a vessel imprint of more intense AF would be revealed upon retinal translocation.


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

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

A2E photobleaching by irradiation at 480 nm for 4 and 8 min. Fluorescence intensity decreases with irradiation and the emission maximum undergoes a hypsochromic shift. Emission peak wavelengths (nm) are indicated adjacent to each trace.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: A2E photobleaching by irradiation at 480 nm for 4 and 8 min. Fluorescence intensity decreases with irradiation and the emission maximum undergoes a hypsochromic shift. Emission peak wavelengths (nm) are indicated adjacent to each trace.
Mentions: The propensity for bisretinoids to undergo photooxidative and photodegradative processes may underlie the decline in RPE lipofuscin fluorescence emission (photobleaching) that has been observed in non-human primates during in vivo fluorescence imaging by adaptive optics scanning laser ophthalmoscopy [48, 71], with cell culture models [72] and in non-cellular assays (Figure 4). Lipofuscin photobleaching may also explain why after surgical repair of some cases of retinal detachment, hyperautofluorescent lines coursing parallel to retinal blood vessels can be visible in fundus AF images [73, 74] (Figure 5). The hyperautofluorescent imprint has been interpreted as indicating a change in the position of the vessel relative to the underlying retinal tissue and is visible because of contrasting levels of AF brightness. At any given time, the intensity of fundus AF is likely the difference between fluorophore synthesis on the one hand, and lipofuscin photoxidation/photodegradation in RPE, on the other. Under the shadow of a blood vessel, the formation of bisretinoid from retinaldehyde (with 11-cis being converted to all-trans-retinal) would likely continue unabated [20, 30, 75–77] but lipofuscin photooxidation and photobleaching would be substantially reduced. As a result, a vessel imprint of more intense AF would be revealed upon retinal translocation.

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