gms | German Medical Science

The bisretinoids that constitute the lipofuscin of retinal pigment epithelial (RPE) form as adducts of visual cycle retinaldehyde. Accordingly, the fluorescence properties of RPE lipofuscin are explained by this origin. An understanding of the bisretinoids of RPE lipofuscin is important both because these fluorophores are the source of short wavelength fundus autofluorescence and because it is of interest with respect to the pathogenesis of macular degeneration. The increase in bisretinoid lipofuscin formation in Abca4-/- mice is accompanied by photoreceptor cell degeneration. These mutant mice are also more susceptible to retinal light damage than are wild-type mice. While these fluorophores may be resistant to lysosomal degradation they undergo photocleavage, thereby releasing damaging dicarbonyls. Interest in a role for RPE lipofuscin in AMD stems from its age-related increase, an accumulation that is more pronounced in central retina, a propensity for adverse effects on cells and demonstrated links to drusen. The contributions to AMD pathogenesis from RPE lipofuscin would operate within the context of background genetic risk and in relation to other factors such as antioxidant status.