CLC number: R774.5
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2013-08-13
Cited: 5
Clicked: 6487
Ya-lin Wu, Jie Li, Ke Yao. Structures and biogenetic analysis of lipofuscin bis-retinoids[J]. Journal of Zhejiang University Science B, 2013, 14(9): 763-773.
@article{title="Structures and biogenetic analysis of lipofuscin bis-retinoids",
author="Ya-lin Wu, Jie Li, Ke Yao",
journal="Journal of Zhejiang University Science B",
volume="14",
number="9",
pages="763-773",
year="2013",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1300051"
}
%0 Journal Article
%T Structures and biogenetic analysis of lipofuscin bis-retinoids
%A Ya-lin Wu
%A Jie Li
%A Ke Yao
%J Journal of Zhejiang University SCIENCE B
%V 14
%N 9
%P 763-773
%@ 1673-1581
%D 2013
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1300051
TY - JOUR
T1 - Structures and biogenetic analysis of lipofuscin bis-retinoids
A1 - Ya-lin Wu
A1 - Jie Li
A1 - Ke Yao
J0 - Journal of Zhejiang University Science B
VL - 14
IS - 9
SP - 763
EP - 773
%@ 1673-1581
Y1 - 2013
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1300051
Abstract: age-related macular degeneration (AMD) is still an incurable blinding eye disease because of complex pathogenic mechanisms and unusual diseased regions. With the use of chemical biology tools, great progress has been achieved in improving the understanding of AMD pathogenesis. The severity of AMD is, at least in part, linked to the non-degradable lipofuscin bis-retinoids in retinal pigment epithelial (RPE). This material is thought to result from the lifelong accumulation of lysosomal residual bodies containing the end products derived from the daily phagocytosis of rod outer segments by RPE cells. Here, we present previously recognized bis-retinoids with focus on structures and biosynthetic pathways. In addition to a brief discussion on the mutual conversion relationships of bis-retinoids, future perspectives and the medical relevance of such studies on these lipofuscin constituents are also highlighted.
[1]Allikmets, R., Singh, N., Sun, H., Shroyer, N.F., Hutchinson, A., Chidambaram, A., Gerrard, B., Baird, L., Stauffer, D., Peiffer, A., et al., 1997. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat. Genet., 15(3):236-246.
[2]Anderson, R.E., Maude, M.B., 1970. Phospholipids of bovine outer segments. Biochemistry, 9(18):3624-3628.
[3]Ben-Shabat, S., Itagaki, Y., Jockusch, S., Sparrow, J.R., Turro, N.J., Nakanishi, K., 2002. Formation of a nonaoxirane from A2E, a lipofuscin fluorophore related to macular degeneration, and evidence of singlet oxygen involvement. Angew. Chem. Int. Ed., 41(5):814-817.
[4]Birnbach, C.D., Jarvelainen, M., Possin, D.E., Milam, A.H., 1994. Histopathology and immunocytochemistry of the neurosensory retina in fundus flavimaculatus. Ophthalmology, 101(7):1211-1219.
[5]Borhan, B., Souto, M.L., Imai, H., Shichida, Y., Nakanishi, K., 2000. Movement of retinal along the visual transducin path. Science, 288(5474):2209-2212.
[6]Bressler, N.M., Bressler, S.B., Fine, S.L., 1988. Age-related macular degeneration. Surv. Ophthalmol., 32(6):375-413.
[7]Briggs, C.E., Rucinski, D., Rosenfeld, P.J., Hirose, T., Berson, E.L., Dryja, T.P., 2001. Mutations in ABCR (ABCA4) in patients with Stargardt macular degeneration or cone-rod degeneration. Invest. Ophthalmol. Vis. Sci., 42(10):2229-2236.
[8]Broniec, A., Pawlak, A., Sarna, T., Wielgus, A., Roberts, J., Land, E., Truscott, T., Edge, R., Navaratnam, S., 2005. Spectroscopic properties and reactivity of free radical forms of A2E. Free Radic. Biol. Med., 38(8):1037-1046.
[9]Burns, M.E., Baylor, D.A., 2001. Activation, deactivation, and adaptation in vertebrate photoreceptor cells. Annu. Rev. Neurosci., 24(1):779-805.
[10]Clancy, C., Krogmeier, J.R., Pawlak, A., Rozanowska, M., Sarna, T., Dunn, R.C., Simon, J.D., 2000. Atomic force microscopy and near-field scanning optical microscopy measurements of single human retinal lipofuscin granules. J. Phys. Chem. B, 104(51):12098-12101.
[11]Delori, F.C., Staurenghi, G., Arend, O., Dorey, C.K., Goger, D.G., Weiter, J.J., 1995. In vivo measurement of lipofuscin in Stargardt’s disease-fundus flavimaculatus. Invest. Ophthalmol. Vis. Sci., 36(11):2327-2331.
[12]Delori, F.C., Fleckner, M.R., Goger, D.G., Weiter, J.J., Dorey, C.K., 2000. Autofluorescence distribution associated with drusen in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci., 41(2):496-504.
[13]Dillon, J., Wang, Z., Avalle, L.B., Gaillard, E.R., 2004. The photochemical oxidation of A2E results in the formation of a 5,8,5′,8′-bis-furanoid oxide. Exp. Eye Res., 79(4):537-542.
[14]Ducroq, D., Rozet, J., Gerber, S., Perrault, I., Barbet, F., Hanein, S., Hakiki, S., Dufier, J., Munnich, A., Hamel, C., et al., 2002. The ABCA4 gene in autosomal recessive cone-rod dystrophies. Am. J. Hum. Genet., 71(6):1480-1482.
[15]Duhamel, L., Guillemont, J., Poirier, J.M., Chabardes, P., 1991. A new prenylation method using the lithium enolate of prenal. Reaction with aldehydes and α,β-unsaturated aldehydes. Tetrahedron Lett., 32(35):4495-4498.
[16]Eagle, R.C.Jr., Lucier, A.C., Bernardino, V.B., Yanoff, M., 1980. Retinal pigment epithelial abnormalities in fundus flavimaculatus: a light and electron microscopic study. Ophthalmology, 87(12):1189-1200.
[17]Eldred, G.E., Katz, M.L., 1988. Fluorophores of the human retinal pigment opithelium: separation and spectral characterization. Exp. Eye Res., 47(1):71-86.
[18]Eldred, G.E., Lasky, M.R., 1993. Retinal age pigments generated by self-assembling lysosomotrophic detergents. Nature, 361(6414):724-726.
[19]Feeney-Burns, L., 1980. The pigments of the retinal pigment epithelium. Curr. Top. Eye Res., 2:119-178.
[20]Feeney-Burns, L., Hilderbrand, E.S., Eldridge, S., 1984. Aging human RPE: morphometric analysis of macular, equatorial, and peripheral cells. Invest. Ophthalmol. Vis. Sci., 25(2):195-200.
[21]Fishkin, N.E., Sparrow, J.R., Allikmets, R., Nakanishi, K., 2005. Isolation and characterization of a retinal pigment epithelial cell fluorophore: an all-trans-retinal dimer conjugate. PNAS, 102(20):7091-7096.
[22]Fukui, T., Yamamoto, S., Nakano, K., Tsujikawa, M., Morimura, H., Nishida, K., Ohguro, N., Fujikado, T., Irifune, M., Kuniyoshi, K., et al., 2002. ABCA4 gene mutations in Japanese patients with Stargardt disease and retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci., 43(9):2819-2824.
[23]Gelasco, A., Crouch, R.K., Knapp, D.R., 2000. Intrahelical arrangement in the integral membrane protein rhodopsin investigated by site-specific chemical cleavage and mass spectrometry. Biochemistry, 39(16):4907-4914.
[24]Gerber, S., Rozet, J.M., van de Pol, T., Hoyng, C.B., Munnich, A., Blankenagel, A., Kaplan, J., Cremers, F.P., 1998. Complete exon-intron structure of the retina-specific ATP binding transporter gene (ABCR) allows the identification of novel mutations underlying Stargardt disease. Genomics, 48(1):139-142.
[25]Golczak, M., Maeda, A., Bereta, G., Maeda, T., Kiser, P.D., Hunzelmann, S., Lintig, J., Blaner, W.S., Palczewski, K., 2008. Metabolic basis of visual cycle inhibition by retinoid and nonretinoid compounds in the vertebrate retina. J. Biol. Chem., 283(15):9543-9554.
[26]Isin, B., Rader, A.J., Dhiman, H.K., Klein-Seetharaman, J., Bahar, I., 2006. Predisposition of the dark state of rhodopsin to functional changes in structure. Proteins, 65(4):970-983.
[27]Jäger, S., Palczewski, K., Hofmann, K.P., 1996. Opsin/ all-trans-retinal complex activates transducin by different mechanisms than photolyzed rhodopsin. Biochemistry, 35(9):2901-2908.
[28]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 cell lipofuscin. J. Biol. Chem., 280(48):39732-39739.
[29]Kennedy, C.J., Rakoczy, P.E., Constable, I.J., 1995. Lipofuscin of the retinal pigment epithelium: a review. Eye, 9(6):763-771.
[30]Kim, S., Jockusch, S., Itagaki, Y., Turro, N.J., Sparrow, J.R., 2008. Mechanisms involved in A2E oxidation. Exp. Eye Res., 86(6):975-982.
[31]Kim, S.R., Fishkin, N., Kong, J., Nakanishi, K., Allikmets, R., Sparrow, J.R., 2004. Rpe65 Leu450Met variants is associated with reduced levels of the retinal pigment epithelium lipofuscin fluorophore A2E and iso-A2E. PNAS, 101(32):11668-11672.
[32]Kim, S.R., He, J., Yanase, E., Jang, Y., Berova, N., Sparrow, J.R., Nakanishi, K., 2007. Characterization of dihydro-A2PE: an intermediate in the A2E biosynthetic pathway. Biochemistry, 46(35):10122-10129.
[33]Kliffen, M., van der Schaft, T., Mooy, C.M., de Jong, P.T., 1997. Morphologic changes in age-related maculopathy. Microsc. Res. Tech., 36(2):106-122.
[34]Liu, J., Itagaki, Y., Ben-Shabat, S., Nakanishi, K., Sparrow, J. R., 2000. The biosynthesis of A2E, a fluorophore of aging retina, involves the formation of the precursor, A2-PE, in the photoreceptor outer segment membrane. J. Biol. Chem., 275(38):29354-29360.
[35]Liu, J., Liu, M.Y., Nguyen, J.B., Bhagat, A., Mooney, V., Yan, E.C., 2011. Thermal properties of rhodopsin: insight into the molecular mechanism of dim-light vision. J. Biol. Chem., 286(31):27622-27629.
[36]Maiti, P., Kong, J., Kim, S.R., Sparrow, J.R., Allikmets, R., Rando, R.R., 2006. Small molecule RPE65 antagonists limit the visual cycle and prevent lipofuscin formation. Biochemistry, 45(3):852-860.
[37]Mannich, C., Krösche, W., 1912. Ueber ein kondensationsprodukt aus formaldehyd, ammoniak und antipyrin. Archiv. der Pharmazie, 250(1):647-667 (in German).
[38]Martinez-Mir, A., Paloma, E., Allikmets, R., Ayuso, C., del Rio, T., Dean, M., Vilageliu, L., Gonzàlez-Duarte, R., Balcells, S., 1998. Retinitis pigmentosa caused by a homozygous mutation in the Stargardt disease gene ABCR. Nat. Genet., 18(1):11-12.
[39]Mata, N.L., Weng, J., Travis, G.H., 2000. Biosynthesis of a major lipofuscin fluorophorein mice and humans with ABCR-mediated retinal and macular degeneration. PNAS, 97(13):7154-7159.
[40]Mather, B., Viswanathan, K., Miller, K., Long, T., 2006. Michael addition reactions in macromolecular design for emerging technologies. Prog. Polym. Sci., 31(5):487-531.
[41]Maugeri, A., Klevering, B.J., Rohrschneider, K., Blankenagel, A., Brunner, H.G., Deutman, A.F., Hoyng, C.B., Cremers, F.P., 2000. Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy. Am. J. Hum. Genet., 67(4):960-966.
[42]Michael, A., 1887. On the addition of sodium acetacetic ether and analogous sodium compounds to unsaturated organic ethers. Am. Chem. J., 9:115.
[43]Molday, R.S., Beharry, S., Ahn, J., Zhong, M., 2006. Binding of N-retinylidene-PE to ABCA4 and a model for its transport across membranes. Adv. Exp. Med. Biol., 572:465-470.
[44]Ng, K.P., Gugiu, B., Crabb, J.W., 2008. Retinal pigment epithelium lipofuscin proteomics. Mol. Cell. Proteomics, 7(7):1397-1405.
[45]Okada, T., Ernst, O.P., Palczewski, K., Hofmann, K.P., 2001. Activation of rhodopsin: new insights from structural and biochemical studies. Trends Biochem. Sci., 26(5):318-324.
[46]Parish, C.A., Hashimoto, M., Nakanishi, K., Dillon, J., Sparrow, J., 1998. Isolation and one-step preparation of A2E and iso-A2E, fluorophores from human retinal pigment epithelium. PNAS, 95(25):14609-14613.
[47]Poincelot, R.P., Millar, P.G., Kimbel, R.L., Abramson, E.W., 1969. Lipid to protein chromophore transfer in the photolysis of visual pigments. Nature, 221(5177):256-257.
[48]Rabb, M.F., Tso, M.O., Fishman, G.A., 1986. Cone-rod dystrophy. A clinical and histopathologic report. Ophthalmology, 93(11):1443-1451.
[49]Radu, R.A., Mata, N.L., Nusinowitz, S., Liu, X., Sieving, P.A., Travis, G.H., 2003. Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt’s macular degeneration. PNAS, 100(8):4742-4747.
[50]Radu, R.A., Han, Y., Bui, T.V., Nusinowitz, S., Bok, D., Lichter, J., Widder, K., Travis, G.H., Mata, N.L., 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(12):4393-4401.
[51]Rando, R.R., 1996. Polyenes and vision. Chem. Biol., 3(4):255-262.
[52]Ren, R., Sakai, N., Nakanishi, K., 1997. Total synthesis of the ocular age pigment A2-E: a convergent pathway. J. Am. Chem. Soc., 119(15):3619-3620.
[53]Rozet, J.M., Gerber, S., Ghazi, I., Perrault, I., Ducroq, D., Souied, E., Cabot, A., Dufier, J.L., Munnich, A., Kaplan, J., 1999. Mutations of the retinal specific ATP binding transporter gene (ABCR) in a single family segregating both autosomal recessive retinitis pigmentosa RP19 and Stargardt disease: evidence of clinical heterogeneity at this locus. J. Med. Genet., 36(6):447-451.
[54]Sakai, N., Decatur, J., Nakanishi, K., 1996. Ocular age pigment “A2-E”: an unprecedented pyridinium bisretinoid. J. Am. Chem. Soc., 118(6):1559-1560.
[55]Sakmar, T.P., 1997. Rhodopsin: a prototypical G protein-coupled receptor. Prog. Nucleic. Acid Res. Mol. Biol., 59:1-34.
[56]Sarks, S.H., Arnold, J.J., Killingsworth, M.C., Sarks, J.P., 1999. Early drusen formation in the normal and aging eye and their relation to age related maculopathy: a clinicopathological study. Br. J. Ophthalmol., 83(3):358-368.
[57]Shroyer, N.F., Lewis, R.A., Allikmets, R., Singh, N., Dean, M., Leppert, M., Lupski, J.R., 1999. The rod photoreceptor ATP-binding cassette transporter gene, ABCR, and retinal disease: from monogenic to multifactorial. Vision Res., 39(15):2537-2544.
[58]Sparrow, J.R., Cai, B., 2001. Blue light-induced apoptosis of A2E-containing RPE: involvement of caspase-3 and protection by Bcl2. Invest. Ophthalmol. Vis. Sci., 42(6):1356-1362.
[59]Sparrow, J.R., Boulton, M., 2005. RPE lipofuscin and its role in retinal photobiology. Exp. Eye Res., 80(5):595-606.
[60]Sparrow, J.R., Nakanishi, K., Parish, C.A., 2000. The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells. Invest. Ophthalmol. Vis. Sci., 41(7):1981-1989.
[61]Sparrow, J.R., Zhou, J., Ben-Shabat, S., Vollmer, H.R., Itagaki, Y., Nakanishi, K., 2002. Involvement of oxidative mechanism in blue light induced damage to A2E-laden RPE. Invest. Ophthalmol. Vis. Sci., 43(4):1222-1227.
[62]Sparrow, J.R., Fishkin, N., Zhou, J., Cai, B., Jang, Y., Krane, S., Itagaki, Y., Nakanishi, K., 2003a. A2E, a byproduct of the visual cycle. Vision Res., 43(28):2983-2990.
[63]Sparrow, J.R., Vollmer, H.R., Zhou, J., Jang, Y.P., Jockusch, S., Itagaki, Y., Nakanishi, K., 2003b. A2E-epoxides damage DNA in retinal pigment epithelial cells. J. Biol. Chem., 278(20):18207-18213.
[64]Sparrow, J.R., Kim, S.R., Cuervo, A.M., Bandhyopadhyayand, U., 2008. A2E, a pigment of RPE lipofuscin is generated from the precursor A2PE by a lysosomal enzyme activity. Adv. Exp. Med. Biol., 613:393-398.
[65]Sparrow, J.R., Kim, S.R., Wu, Y., 2010a. Experimental approaches to the study of A2E, a bisretinoid constituent of the lipofuscin of retinal pigment epithelium. Methods Mol. Biol., 652:315-327.
[66]Sparrow, J.R., Wu, Y., Takayuki, N., Yoon, K., Yamamoto, K., Zhou, J., 2010b. Fundus autofluorescence and the bisretinoids of retina. Photochem. Photobiol. Sci., 9(11):1480-1489.
[67]Sparrow, J.R., Yoon, K., Wu, Y., Yamamoto, K., 2010c. Interpretations of fundus autofluorescence from studies of the bisretinoids of retina. Invest. Ophthalmol. Vis. Sci., 51(9):4351-4357.
[68]Sparrow, J.R., Wu, Y., Kim, C.Y., Zhou, J., 2010d. Phospholipid meets all-trans-retinal: the making of RPE bisretinoids. J. Lipid Res., 51(2):247-261.
[69]Sparrow, J.R., Gregory-Roberts, E., Yamamoto, K., Blonska, A., Ghosh, S.K., Ueda, K., Zhou, J., 2012. The bisretinoids of retinal pigment epithelium. Prog. Retin. Eye Res., 31(2):121-135.
[70]Sun, H., Molday, R.S., Nathans, J., 1999. Retinal stimulates ATP hydrolysis by purified and reconstituted ABCR, the photoreceptor-specific ATP-binding cassette transporter responsible for Stargardt disease. J. Biol. Chem., 274(12):8269-8281.
[71]Telander, D.G., 2011. Inflammation and age-related macular degeneration (AMD). Semin. Ophthalmol., 26(3):192-197.
[72]Thomas, A.F., Guntzdubini, R., 1976. The ‘aldol condensation’ of citral and related reactions. Helv. Chim. Acta, 59(6):2261-2267.
[73]Wang, Z., Keller, L.M., Dillon, J., Gaillard, E.R., 2006. Oxidation of A2E results in the formation of highly reactive aldehydes and ketones. Photochem. Photobiol., 82(5):1251-1257.
[74]Weng, J., Mata, N.L., Azarian, S.M., Tzekov, R.T., Birch, D.G., Travis, G.H., 1999. Insights into the function of Rim protein in photoreceptors and etiology of Stargardt’s disease from the phenotype in abcr knockout mice. Cell, 98(1):13-23.
[75]Wu, Y., Fishkin, N.E., Pande, A., Pande, J., Sparrow, J.R., 2009. Novel lipofuscin bisretinoids prominent in human retina and in a model of recessive Stargardt disease. J. Biol. Chem., 284(30):20155-20166.
[76]Wu, Y., Yanase, E., Feng, X., Siegel, M., Sparrow, J., 2010. Structural characterization of bisretinoid A2E photocleavage products and implications for age-related macular degeneration. PNAS, 107(16):7275-7280.
[77]Wu, Y., Zhou, J., Fishkin, N.E., Rittman, B.E., Sparrow, J.R., 2011. Enzymatic degradation of A2E, an RPE lipofuscin pigment. J. Am. Chem. Soc., 133(4):849-857.
[78]Yamamoto, K., Yoon, K.D., Ueda, K., Hashimoto, M., Sparrow, J.R., 2011. A novel bisretinoid of retina is an adduct on glycerophosphoethanolamine. Invest. Ophthalmol. Vis. Sci., 52(12):9084-9090.
Open peer comments: Debate/Discuss/Question/Opinion
<1>