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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

Structures and absorbance maxima (λmax) of some bisretinoid fluorophores in retinal pigment epithelium (RPE) lipofuscin. Absorbance maxima can be assigned to each of the side-arms of the molecules.
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Figure 2: Structures and absorbance maxima (λmax) of some bisretinoid fluorophores in retinal pigment epithelium (RPE) lipofuscin. Absorbance maxima can be assigned to each of the side-arms of the molecules.

Mentions: RPE lipofuscin consists of a complex mixture of fluorophores that have been identified in by chromatography and mass spectrometry and characterized structurally; all of the known bisretinoid lipofuscin pigments have been detected in human eyes [26] (Figure 2). These fluorophores include the pyridinium-containing molecules A2-glycerophosphoethanolamine (A2-GPE) [27], A2E and isomers of A2E [28–36], dimers of all-trans-retinal having a cyclohexadiene head group (all-trans-retinal dimer) [33, 37] and the associated protonated Schiff base conjugate [37] and the uncharged A2-DHP-PE (A2-dihydropyridine-phosphatidylethanolamine) [38]. Higher molecular weight adducts also form when aldehyde-bearing cleavage products of bisretinoid react with intact bisretinoid molecules [39]. Other molecular constituents of RPE lipofuscin are adducts of CEP (2-(ω-carboxyethyl)-pyrrole) [40], HNE (4-hydroxynonenal) and MDA (malondialdehyde) [41] that are derived from oxidative fragmentation of lipid. Products of lipid oxidation are generally non-fluorescent or blue-emitting fluorophores [42, 43] and in this case could be generated by the photoreactivity of other lipofuscin fluorophores. Little or no protein is present in RPE lipofuscin [40]. Accumulation of bisretinoids in RPE cells is unlikely to depend on an inhibition of lysosomal enzyme activity, since this fluorescent material is amassed in all healthy eyes beginning at early ages [44].


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

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

Structures and absorbance maxima (λmax) of some bisretinoid fluorophores in retinal pigment epithelium (RPE) lipofuscin. Absorbance maxima can be assigned to each of the side-arms of the molecules.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Structures and absorbance maxima (λmax) of some bisretinoid fluorophores in retinal pigment epithelium (RPE) lipofuscin. Absorbance maxima can be assigned to each of the side-arms of the molecules.
Mentions: RPE lipofuscin consists of a complex mixture of fluorophores that have been identified in by chromatography and mass spectrometry and characterized structurally; all of the known bisretinoid lipofuscin pigments have been detected in human eyes [26] (Figure 2). These fluorophores include the pyridinium-containing molecules A2-glycerophosphoethanolamine (A2-GPE) [27], A2E and isomers of A2E [28–36], dimers of all-trans-retinal having a cyclohexadiene head group (all-trans-retinal dimer) [33, 37] and the associated protonated Schiff base conjugate [37] and the uncharged A2-DHP-PE (A2-dihydropyridine-phosphatidylethanolamine) [38]. Higher molecular weight adducts also form when aldehyde-bearing cleavage products of bisretinoid react with intact bisretinoid molecules [39]. Other molecular constituents of RPE lipofuscin are adducts of CEP (2-(ω-carboxyethyl)-pyrrole) [40], HNE (4-hydroxynonenal) and MDA (malondialdehyde) [41] that are derived from oxidative fragmentation of lipid. Products of lipid oxidation are generally non-fluorescent or blue-emitting fluorophores [42, 43] and in this case could be generated by the photoreactivity of other lipofuscin fluorophores. Little or no protein is present in RPE lipofuscin [40]. Accumulation of bisretinoids in RPE cells is unlikely to depend on an inhibition of lysosomal enzyme activity, since this fluorescent material is amassed in all healthy eyes beginning at early ages [44].

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