Interpretations of fundus autofluorescence from studies of the bisretinoids of the retina - PubMed (original) (raw)

Interpretations of fundus autofluorescence from studies of the bisretinoids of the retina

Janet R Sparrow et al. Invest Ophthalmol Vis Sci. 2010 Sep.

Abstract

Elevated fundus autofluorescence signals can reflect enhanced lipofuscin in RPE cells, augmented fluorescence due to photooxidation, and/or excess bisretinoid fluorophores in photoreceptor cells due to mishandling of vitamin A aldehyde by dysfunctional cells.

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Figures

Figure 1.

Figure 1.

(A) Fundus autofluorescence image obtained from an adult with healthy retinal status: cSLO and 488 nm excitation. (B) Fundus images obtained from an individual with GA: autofluorescence (left) and color fundus (right) photographs. A zone of increased autofluorescence signal (arrows) surrounds an irregular and nonhomogeneous zone of reduced AF, with uniform loss of AF occurring most centrally.

Figure 2.

Figure 2.

The fluorescence intensity of RPE lipofuscin bisretinoids increased as the abundance of the pigments was augmented. A2E and all-_trans_-retinal dimer were injected into a UPLC (ultra-performance liquid chromatography) system, with reversed-phase column, at the indicated amounts in a 5-μL volume, and the samples were monitored with a fluorescence detector. UV-visible absorbances were monitored but are not shown. Insets: structures, and absorbance maxima (λmax) of A2E and all-_trans_-retinal dimer.

Figure 3.

Figure 3.

Fluorescence intensity of RPE lipofuscin bisretinoids was increased after photooxidation on the short arm of the molecule. Samples of A2E were irradiated at 430 nm to generate photooxidation products (oxo-A2E 1, 2, and 3) and then analyzed by reversed-phase UPLC (ultra-performance liquid chromatography) with online monitoring of absorbance (black trace) and fluorescence (red trace). Fluorescence efficiency per absorbed photon, calculated as fluorescence peak height/absorbance peak height, was 83.6 for oxo-A2E 1, 36.1 for oxo-A2E 3, and 6.7 for A2E. Note that oxo-A2E 2 exhibited little or no fluorescence.

Figure 4.

Figure 4.

Bisretinoid formation in impaired photoreceptors can greatly exceed that generated in healthy photoreceptor cell outer segments. (A) HPLC quantitation of all-_trans_-retinal (retinoid precursor of RPE lipofuscin) and two bisretinoids (all-_trans_-retinal dimer and A2PE) that form in photoreceptor cells via the lipofuscin biosynthetic pathway. Eyecups of RCS and control (RCS rdy+) albino rats, age 1 month, included RPE and neural retina. Under normal conditions, phospholipase D-mediated phosphate hydrolysis of A2PE (dashed line in structure) in RPE cell lysosomes releases A2E, and the latter then accumulates in RPE. However, in the RCS rat, because of the failure to phagocytose, most of the pigment generated within the A2PE/A2E pathway remains as A2PE. (B) Fluorescence emission spectra of A2E and A2PE recorded at an excitation of 488 nm. The slightly greater fluorescence intensity of A2PE probably reflects an excitation maximum (∼449 nm) that is closer to 488 nm than the excitation maximum of A2E (∼439 nm).

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