Bisretinoid Photodegradation Is Likely Not a Good Thing

Abstract

Retinaldehyde adducts (bisretinoids) accumulate in retinal pigment epithelial (RPE) cells as lipofuscin. Bisretinoids are implicated in some inherited and age-related forms of macular degeneration that lead to the death of RPE cells and diminished vision. By comparing albino and black-eyed mice and by rearing mice in darkness and in cyclic light, evidence indicates that bisretinoid fluorophores undergo photodegradation in the eye (Ueda et al. Proc Natl Acad Sci 113:6904-6909, 2016). Given that the photodegradation products modify and impair cellular and extracellular molecules, these processes likely impart cumulative damage to retina.

Keywords: ABCA4-associated disease; Age-related macular degeneration; Bisretinoid; Lipofuscin; Retinal degeneration; Retinaldehyde; Visual cycle; Vitamin E.

Fig. 49.1

The RPE bisretinoid A2E accumulates in both light- and dark-reared mice, levels are reduced in light-reared versus dark-reared albino mice, and levels are modulated by antioxidant status. Analysis by reverse-phase HPLC. (a): Quantitation of the bisretinoid A2E in 6-month-old black C57BL/6J and albino C57BL/6J–^c2j mice that were dark reared or cyclic light reared from birth. Means ± SEM of five or seven independent samples six to eight eyes/sample p-values determined by one-way ANOVA and Tukey’s multiple comparison test and two-tailed t-test. (b, c): Reduction in bisretinoid photooxidation by vitamin E supplementation is detected as reduced bisretinoid loss and measured as increased quantitative fundus autofluorescence (qAF) (b) and increased HPLC-quantified A2E, A2-DHP-PE, and atRAL di-PE (c). Means ± SEM of eight mice, p < 0.05, two-tailed t-test. (a); Two samples (six eyes per sample), ANOVA and Sidak’s multiple comparison test (b). (d): Reduced bisretinoid photooxidation/photodegradation also protects against outer nuclear layer (ONL) thinning. ONL area (microns²) calculated as the sum of the ONL thicknesses in the superior and inferior retina (0.2–2.0 mm from optic nerve head) multiplied by the measurement interval of 200 microns; means ± SEM, two-tailed t-test