Lipofuscin

The age pigments (lipofuscin), which accumulate with age, aie largely made up of these precipitated Hpid-proteia complexes resultiag from such cross-linking. Vitamin E may function to help prevent formation of these complexes. The metaboHc role of antioxidants (qv) such as vitamin E in animal tissues, however, remains quite controversial. 

An assumption inherent in the one-wavelength method is that the distribution of lipofuscin is uniform throughout the area of the retina being analyzed. Certainly if lipofuscin concentration... 

Xanthophylls can further inhibit the peroxidation of membrane phospholipids (Lim et al. 1992) and reduce photooxidation of lipofuscin fluorophores (Kim et al. 2006), which are implicated in the pathogenesis of AMD (Sparrow and Boulton 2005). Furthermore, it was shown that light-induced damage to photoreceptors was reduced in quails fed zeaxanthin, with the number of apoptotic photoreceptor cells being inversely related to the concentration of zeaxanthin in the retina (Thomson et al. 2002). 

Moreover, carotenoids may quench electronically excited states and scavenge free radicals formed in the retina, and therefore protect biomolecules from oxidative damage. Due to the low energy level of the first excited triplet state ( Car), carotenoids (Car) can act as efficient acceptors of triplet state energy from photosensitizers (S) (Equation 15.1), such as all-tra .s-retinal, the photosensitizers of lipofuscin (Rozanowska et al., 1998), or singlet oxygen C02) (Equation 15.2) (Cantrell et al., 2003) ... 

Boulton, M, Rozanowska, M, Rozanowski, B, and Wess, T, 2004. The photoreactivity of ocular lipofuscin. Photochem Photobiol Sci 3, 759-764. 

Katz, ML, 2002. Potential role of retinal pigment epithelial lipofuscin accumulation in age-related macular degeneration. Arch Gerontol Geriatr 34, 359-370. 

Lakkaraju, A, Finnemann, SC, and Rodriguez-Boulan, E, 2007. The lipofuscin fluorophore A2E perturbs cholesterol metabolism in retinal pigment epithelial cells. I1 roc Nall Acad Sci USA 104, 11026-11031. 

Maiti, P, Kong, J, Kim, SR, Sparrow, JR, Allikmets, R, and Rando, RR, 2006. Small molecule RPE65 antagonists limit the visual cycle and prevent lipofuscin formation. Biochemistry 45, 852-860. 

Mata, NL, Weng, J, and Travis, GH, 2000. Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCR-mediated retinal and macular degeneration. Proc Natl Acad Sci U SA 97, 7154—7159. 

Mata, NL, Tzekov, RT, Liu, XR, Weng, J, Birch, DG, and Travis, GH, 2001. Delayed, dark-adaptation and lipofuscin accumulation in abcr+/- mice Implications for involvement of ABCR in age-related macular degeneration. Invest Ophthalmol Vis Sci 42, 1685-1690. 

Radu, RA, Mata, NL, Nusinowitz, S, Liu, X, Sieving, PA, and Travis, GH, 2003. Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt s macular degeneration. Proc Natl Acad Sci USA 100, 4742- 4747. 

Radu, RA, Han, Y, Bui, TV, Nusinowitz, S, Bok, D, Lichter, J, Widder, K, Travis, GH, and Mata, NL, 2005. Reductions in serum vitamin A arrest accumulation of toxic retinal fluorophores A potential therapy for treatment of lipofuscin-based retinal diseases. Invest Ophthalmol Vis Sci 46, 4393 4401. 

Rozanowska, M, Wessels, J, Boulton, M, Burke, JM, Rodgers, MA, Truscott, TG, and Sarna, T, 1998. Blue light-induced singlet oxygen generation by retinal lipofuscin in non-polar media. Free Radio Biol Med 24, 1107-1112. 

Rozanowska, M, Korytowski, W, Rozanowski, B, Skumatz, C, Boulton, ME, Burke, JM, and Sarna, T, 2002. Photoreactivity of aged human RPE melanosomes A comparison with lipofuscin. Invest Ophthalmol Vis Sci 43, 2088-2096. 

Rdzanowska, M and Rozanowski, B, 2008. Visual transduction and age-related changes in lipofuscin. In Tombran-Tink, J and Barnstable, CJ (Eds.), Ophthalmology Research The Visual Transduction Cascade. The Humana Press Inc., Totowa, NJ, pp. 405 146. 

Sundelin, SP and Nilsson, SE, 2001. Lipofuscin-formation in retinal pigment epithelial cells is reduced by antioxidants. Free Radio Biol Med 31, 217-225. 

The Carotenoids of Macular Pigment and Bisretinoid Lipofuscin Precursors in Photoreceptor Outer Segments... 

FIGURE 16.4 Precursors of RPE cell lipofuscin form in the outer segments of photoreceptor cells. The retina of normal rat (A, B) and the Royal College of Surgeons (RCS) rat (C, D) viewed under the phase contrast (A, C) and the epifluorescence microscopy (B, D). In the normal rat, autofluorescent material accumulates as lipofuscin in RPE cells (arrows). In the RCS, due to a defect in RPE cell phagocytosis, shed outer segment membrane builds up at the photoreceptor-RPE interface the autofluorescence in this debris is attributable to lipofuscin precursors that form in photoreceptor outer segments. 

Biosynthetic studies of A2E, a major fluorophore of RPE lipofuscin. J Biol Chem. 277, 7183-7190. Bhosale, P, Larson, A.J., Frederick, J.M., Southwick, K., Thulin, C.D., Bernstein, P.S., 2004. Identification and characterization of a Pi isoform of glutathioine S-transferase (GSTP1) as a zeaxanthin-binding protein in the macula of the human eye. J Biol Chem. 279, 49447 19454. 

Dietary modification of human macular pigment density. Invest Ophthalmol Vis Sci. 38, 1795-1801. Jang, Y.P., Matsuda, H., Itagaki, Y., Nakanishi, K., Sparrow, J.R., 2005. Characterization of peroxy-A2E and furan-A2E photooxidation products and detection in human and mouse retinal pigment epithelial cells lipofuscin. J Biol Chem. 280, 39732-39739. 

Kim, S.R., Jang, Y.P., Jockusch, S., Fishkin, N.E., Turro, N.J., Sparrow, J.R., 2007b. The all-trans-retinal dimer series of lipofuscin pigments in retinal pigment epithelial cells in a recessive Stargardt disease model. Pmc Natl Acad Sci USA. 104, 19273-19278. 

---