Fundus autofluorescence and the bisretinoids of retina

Abstract

Imaging of the human fundus of the eye with excitation wavelengths in the visible spectrum reveals a natural autofluorescence, that in a healthy retina originates primarily from the bisretinoids that constitute the lipofuscin of retinal pigment epithelial (RPE) cells. Since the intensity and distribution of fundus autofluorescence is altered in the presence of retinal disease, we have examined the fluorescence properties of the retinal bisretinoids with a view to aiding clinical interpretations. As is also observed for fundus autofluorescence, fluorescence emission from RPE lipofuscin was generated with a wide range of exciting wavelengths; with increasing excitation wavelength, the emission maximum shifted towards longer wavelengths and spectral width was decreased. These features are consistent with fluorescence generation from a mixture of compounds. While the bisretinoids that constitute RPE lipofuscin all fluoresced with maxima that were centered around 600 nm, fluorescence intensities varied when excited at 488 nm, the excitation wavelength utilized for fundus autofuorescence imaging. For instance the fluorescence efficiency of the bisretinoid A2-dihydropyridine-phosphatidylethanolamine (A2-DHP-PE) was greater than A2E and relative to both of the latter, all-trans-retinal dimer-phosphatidylethanolamine was weakly fluorescent. On the other hand, certain photooxidized forms of the bisretinoids present in both RPE and photoreceptor cells were more strongly fluorescent than the parent compound. We also sought to evaluate whether diffuse puncta of autofluorescence observed in some retinal disorders of monogenic origin are attributable to retinoid accumulation. However, two retinoids of the visual cycle, all-trans-retinyl ester and all-trans-retinal, did not exhibit fluorescence at 488 nm excitation.

Comparison of Fundus Autofluorescence with Photopic and Scotopic Fine Matrix Mapping in Patients with Retinitis Pigmentosa: 4- to 8-Year Follow-up

“…7,31 The loss of outer retinal structure detailed above suggests that normal background AF outside the ring is not dependent on continued retinoid recycling; the fluorescent half-life of lipofuscin may be prolonged in vivo or there may be other more stable fluorophores, resistant to light and enzyme degradation. 32 The data suggest that rod system dysfunction in RP progressively encroaches upon central macular areas with consequent cone dysfunction and progressive visual field constriction. This chronic photoreceptor dysfunction likely results in progressive fluorophore accumulation and the development of a ring of increased AF, at a time and location that is closely coincident with advancing cone system dysfunction.…”

Complement modulation in the retinal pigment epithelium rescues photoreceptor degeneration in a mouse model of Stargardt disease

“…Fluorescent bisretinoid-lipofuscin pigments can be visualized by fundus autofluorescence imaging (17,18) and are responsible for the "dark choroid" seen in STGD1 patients on fluorescein angiography (19). One of the major lipofuscin components in the RPE of Abca4 −/− mice and STGD1 patients is N-retinylidene-N-retinylethanolamine (A2E) (15).…”

Effects of Coagulation on the Autofluorescence Pattern of ARPE-19 Cells: An in vitro Study

“…FAF appears to correlate directly with the accumulation of lipofuscin and its component, A2E, within RPE [21,22]. In a number of pathological conditions, FAF increases and appears to be the result of inadequate degradation of POS [23].…”