Lipofuscin and N-Retinylidene-N-Retinylethanolamine (A2E) Accumulate in Retinal Pigment Epithelium in Absence of Light Exposure
Open accessAbstract
The age-dependent accumulation of lipofuscin in the retinal pigment epithelium (RPE) has been associated with the development of retinal diseases, particularly age-related macular degeneration and Stargardt disease. A major component of lipofuscin is the bis-retinoid N-retinylidene-N-retinylethanolamine (A2E). The current model for the formation of A2E requires photoactivation of rhodopsin and subsequent release of all-trans-retinal. To understand the role of light exposure in the accumulation of lipofuscin and A2E, we analyzed RPEs and isolated rod photoreceptors from mice of different ages and strains, reared either in darkness or cyclic light. Lipofuscin levels were determined by fluorescence imaging, whereas A2E levels were quantified by HPLC and UV-visible absorption spectroscopy. The identity of A2E was confirmed by tandem mass spectrometry. Lipofuscin and A2E levels in the RPE increased with age and more so in the Stargardt model Abca4(-/-) than in the wild type strains 129/sv and C57Bl/6. For each strain, the levels of lipofuscin precursor fluorophores in dark-adapted rods and the levels and rates of increase of RPE lipofuscin and A2E were not different between dark-reared and cyclic light-reared animals. Both 11-cis- and all-trans-retinal generated lipofuscin-like fluorophores when added to metabolically compromised rod outer segments; however, it was only 11-cis-retinal that generated such fluorophores when added to metabolically intact rods. The results suggest tha…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Immunohistology showed RPE65 in the outer segments of cone-like photoreceptors in Nrl-/- mice.
“Immunohistology showed RPE65 to be present in the OS of these cone-like photoreceptors (Figure 6, B-C) (Boyer et al., 2012b).”
From New insights into retinoid metabolism and cycling within the retina (2013) · cites this paper as Boyer et al., 2012b
Adding 11-cis retinal directly to rods produces lipofuscin precursors even without light.
“Furthermore, direct addition of 11-cis retinal to rod photoreceptors results in the generation of lipofuscin precursors in the absence of light.”
From New insights into retinoid metabolism and cycling within the retina (2013) · cites this paper as Boyer et al., 2012a
New evidence suggests that 11-cis retinal itself could be an important source of lipofuscin and A2E.
“While it is clear that retinoids are involved in lipofuscin, recent evidence shows 11-cis retinal itself may be a major source of lipofuscin and A2E (Boyer et al., 2012a).”
From New insights into retinoid metabolism and cycling within the retina (2013) · cites this paper as Boyer et al., 2012a
Dark-reared mice have lipofuscin and precursor levels equal to those of mice reared in cyclic light.
“These results are based on the finding that mice raised in the dark have the same levels of lipofuscin and lipofuscin precursors as animals raised in cyclic light.”
From New insights into retinoid metabolism and cycling within the retina (2013) · cites this paper as Boyer et al., 2012a
Cites
The Human ATP-Binding Cassette (ABC) Transporter SuperfamilyPreprint
Dean, M. C., Rzhetsky, A., & Allikmets, R. L. (2001) · Genome Research · doi:10.1101/gr.184901 · Cited by 1,758 · see citing works
Allikmets, R., Singh, N., Sun, H., Shroyer, N. F., Hutchinson, A., Chidambaram, A., Gerrard, B., Baird, L., Stauffer, D., Peiffer, A., et al. (1997) · Nature Genetics · doi:10.1038/ng0397-236 · Cited by 1,435 · cited 5× · see citing works
“As such, deficiencies in ABCA4 function would lead to an accumulation in N-retinylidene-PE, driving the formation of the precursors of A2E and lipofuscin after photoactivation of rhodopsin.”
BackgroundInfluentialThe renewal of photoreceptor cell outer segments
Young, R. W. (1967) · The Journal of Cell Biology · doi:10.1083/jcb.33.1.61 · Cited by 1,184 · cited 1× · see citing works
“Keeping in mind that 10% ofmouse rod outer segments is being phagocytosed daily by theRPE (46), comparison of the amounts ofA2E found in the retina and the accumulated amounts in the RPE would indicate that A2E and probably other lipofuscin precursors be eliminated even in dark-reared animals.”
BackgroundDelori, F. C., Dorey, C. K., Staurenghi, G., Arend, O., Goger, D. G., & Weiter, J. J. (1995) · PubMed · Cited by 938 · see citing works
Weng, J., Mata, N. L., Azarian, S. M., Tzekov, R. T., Birch, D. G., & Travis, G. H. (1999) · Cell · doi:10.1016/s0092-8674(00)80602-9 · Cited by 881 · cited 6× · see citing works
“Mice that lack Abca4 exhibit a large increase in RPE lipofuscin and bis-retinoid, including A2E, accumulation (17, 20, 21).”
BackgroundResultInfluentialRPE lipofuscin and its role in retinal pathobiology
Sparrow, J. R., & Boulton, M. (2005) · Experimental Eye Research · doi:10.1016/j.exer.2005.01.007 · Cited by 644 · see citing works
Sparrow, J. R., Nakanishi, K., & Parish, C. A. (2000) · PubMed · Cited by 566 · see citing works
Oxidative Damage and Age Related Macular Degeneration
Renganathan, K. (2008) · OhioLink ETD Center (Ohio Library and Information Network) · Cited by 565 · see citing works
(1999) · PubMed · Cited by 539 · see citing works
ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine.
Hamon, Y., Broccardo, C., Chambenoit, O., Luciani, M., Toti, F., Chaslin, S., Freyssinet, J., Devaux, P. F., McNeish, J. D., Marguet, D., et al. (2000) · Nature Cell Biology · doi:10.1038/35017029 · Cited by 529 · see citing works
Parish, C. A., Hashimoto, M., Nakanishi, K., Dillon, J., & Sparrow, J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14609 · Cited by 474 · see citing works
Retinal age pigments generated by self-assembling lysosomotropic detergents
Eldred, G. E., & Lasky, M. R. (1993) · Nature · doi:10.1038/361724a0 · Cited by 461 · see citing works
Mata, N. L., Weng, J., & Travis, G. H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.130110497 · Cited by 456 · see citing works
Terman, A., & Brunk, U. T. (2004) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2003.08.009 · Cited by 451 · see citing works
Ebrey, T. G., & Koutalos, Y. (2001) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(00)00014-8 · Cited by 441 · see citing works
Self-citationAge-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects.
Delori, F. C., Goger, D. G., & Dorey, C. K. (2001) · PubMed · Cited by 424 · see citing works
Photolyzed rhodopsin catalyzes the exchange of GTP for bound GDP in retinal rod outer segments.
Fung, B. K.-K., & Stryer, L. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.5.2500 · Cited by 397 · see citing works
Feeney, L. (1978) · PubMed · Cited by 397 · see citing works
The topography and age relationship of lipofuscin concentration in the retinal pigment epithelium.
Wing, G. L., Blanchard, G. C., & Weiter, J. J. (1978) · PubMed · Cited by 394 · see citing works
Sun, H., Molday, R. S., & Nathans, J. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.12.8269 · Cited by 353 · see citing works
A2E, a lipofuscin fluorophore, in human retinal pigmented epithelial cells in culture.
Sparrow, J. R., Parish, C. A., Hashimoto, M., & Nakanishi, K. (1999) · PubMed · Cited by 312 · see citing works
Wenzel, A., Remé, C. E., Williams, T. P., Hafezi, F., & Grimm, C. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-01-00053.2001 · Cited by 291 · see citing works
PARTICIPATION OF THE RETINAL PIGMENT EPITHELIUM IN THE ROD OUTER SEGMENT RENEWAL PROCESS
Young, R. W., & Bok, D. (1969) · Journal of Cell Biology · doi:10.1083/jcb.42.2.392 · Cited by 271 · see citing works
Liu, J., Itagaki, Y., Ben-Shabat, S., Nakanishi, K., & Sparrow, J. R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m910191199 · Cited by 255 · see citing works
In vivo measurement of lipofuscin in Stargardt's disease--Fundus flavimaculatus.
Delori, F. C., Staurenghi, G., Arend, O., Dorey, C. K., Goger, D. G., & Weiter, J. J. (1995) · PubMed · Cited by 245 · see citing works
Chen, Y., Okano, K., Maeda, T., Chauhan, V., Golczak, M., Maeda, A., & Palczewski, K. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.315432 · Cited by 229 · see citing works
Blue Light-Induced Singlet Oxygen Generation by Retinal Lipofuscin in Non-Polar Media
Rôżanowska, M., Wessels, J. M., Boulton, M. E., Burke, J. M., Rodgers, M. A. J., Truscott, T. G., & Sarna, T. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(97)00395-x · Cited by 227 · see citing works
Mata, N. L., Tzekov, R. T., Liu, X., Weng, J., Birch, D. G., & Travis, G. H. (2001) · PubMed · Cited by 219 · see citing works
Biosynthetic Studies of A2E, a Major Fluorophore of Retinal Pigment Epithelial Lipofuscin
Ben-Shabat, S., Parish, C. A., Vollmer, H. R., Itagaki, Y., Fishkin, N., Nakanishi, K., & Sparrow, J. R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108981200 · Cited by 214 · see citing works
Wang, N., Lan, D., Gerbod-Giannone, M. C., Linsel‐Nitschke, P., Jehle, A. W., Chen, W., Martinez, L. O., & Tall, A. R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307831200 · Cited by 202 · see citing works
Circadian nature of rod outer segment disc shedding in the rat.
LaVail, M. M. (1980) · PubMed · Cited by 199 · see citing works
Allelic variation in ABCR associated with Stargardt disease but not age-related macular degeneration
Stone, E. M., Webster, A. R., Vandenburgh, K., Streb, L. M., Hockey, R. R., Lotery, A. J., & Sheffield, V. C. (1998) · Nature Genetics · doi:10.1038/3798 · Cited by 197 · see citing works
Phospholipid meets all-trans-retinal: the making of RPE bisretinoids
Sparrow, J. R., Wu, Y., Kim, C. Y., & Zhou, J. (2010) · Journal of Lipid Research · doi:10.1194/jlr.r000687 · Cited by 193 · see citing works
Molday, R. S., Zhong, M., & Quazi, F. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2009.02.004 · Cited by 182 · see citing works
Beharry, S., Zhong, M., & Molday, R. S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405216200 · Cited by 174 · see citing works
Rod Outer Segment Retinol Dehydrogenase: Substrate Specificity and Role in Phototransduction
Palczewski, K., Jäger, S., Buczyłko, J., Crouch, R. K., Bredberg, D. L., Hofmann, K. P., Asson–Batres, M. A., & Saari, J. C. (1994) · Biochemistry · doi:10.1021/bi00250a027 · Cited by 173 · see citing works
Self-citationRetinal Pigment Epithelium Lipofuscin Proteomics
Ng, K.-P., Gugiu, B., Renganathan, K., Davies, M. W., Gu, X., Crabb, J. S., Kim, S. R., Różanowska, M. B., Bonilha, V. L., Rayborn, M. E., et al. (2008) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m700525-mcp200 · Cited by 162 · see citing works
Influence of early photoreceptor degeneration on lipofuscin in the retinal pigment epithelium
Katz, M. L., Drea, C. M., Eldred, G. E., Hess, H. H., & Robison, W. G. (1986) · Experimental Eye Research · doi:10.1016/s0014-4835(86)80023-9 · Cited by 149 · see citing works
Wu, Y., Yanase, E., Feng, X., Siegel, M. M., & Sparrow, J. R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913112107 · Cited by 149 · see citing works
Kim, S. R., Jang, Y. P., Jockusch, S., Fishkin, N. E., Turro, N. J., & Sparrow, J. R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708714104 · Cited by 145 · see citing works
(2001) · PubMed · Cited by 136 · see citing works
Katz, M. L., & Robison, W. G. (2002) · Archives of Gerontology and Geriatrics · doi:10.1016/s0167-4943(02)00005-5 · Cited by 122 · see citing works
Limited Roles of Rdh8, Rdh12, and Abca4 in all- trans -Retinal Clearance in Mouse Retina
Maeda, A., Golczak, M., Maeda, T., & Palczewski, K. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.09-3944 · Cited by 92 · see citing works
Katz, M. L. (1996) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(96)01817-9 · Cited by 77 · see citing works
Retinal light damage reduces autofluorescent pigment deposition in the retinal pigment epithelium.
Katz, M. L., & Eldred, G. E. (1989) · PubMed · Cited by 64 · see citing works
Lyubarsky, A., Savchenko, A. B., Morocco, S. B., Daniele, L. L., Redmond, T. M., & Pugh, E. N. (2005) · Biochemistry · doi:10.1021/bi0505363 · Cited by 63 · see citing works
Spatial localization of A2E in the retinal pigment epithelium
Grey, A. C., Crouch, R. K., Koutalos, Y., Schey, K. L., & Ablonczy, Z. (2011) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.10-7020 · Cited by 52 · see citing works
Self-citationBui, T. V., Han, Y., Radu, R. A., Travis, G. H., & Mata, N. L. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m601380200 · Cited by 48 · see citing works
Photooxidation of RPE lipofuscin bisretinoids enhances fluorescence intensity
Kim, S. R., Jang, Y. P., & Sparrow, J. R. (2009) · Vision Research · doi:10.1016/j.visres.2009.09.015 · Cited by 37 · see citing works
Characterization of phospholipase D activity in bovine photoreceptor membranes
Salvador, G. A., & Giusto, N. M. (1998) · Lipids · doi:10.1007/s11745-998-0281-z · Cited by 34 · see citing works
Formation of all- trans Retinol after Visual Pigment Bleaching in Mouse Photoreceptors
Chen, C., Blakeley, L. R., & Koutalos, Y. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-3336 · Cited by 34 · see citing works
Self-citationBlakeley, L. R., Chen, C.-K., Chen, C.-K., Chen, J., Crouch, R. K., Travis, G. H., & Koutalos, Y. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-6694 · Cited by 23 · see citing works
Self-citationMass spectrometry provides accurate and sensitive quantitation of A2E
Gutierrez, D. B., Blakeley, L. R., Goletz, P. W., Schey, K. L., Hanneken, A. M., Koutalos, Y., Crouch, R. K., & Ablonczy, Z. (2010) · Photochemical & Photobiological Sciences · doi:10.1039/c0pp00230e · Cited by 23 · see citing works
Self-citationLipofuscin and A2E Accumulate with Age in the Retinal Pigment Epithelium of Nrl−/− Mice†
Boyer, N. P., Tang, P. H., Higbee, D., Ablonczy, Z., Crouch, R. K., & Koutalos, Y. (2012) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2012.01127.x · Cited by 14 · see citing works
Self-citationChen, C., & Koutalos, Y. (2010) · Photochemical & Photobiological Sciences · doi:10.1039/c0pp00124d · Cited by 10 · see citing works
Self-citationBoyer, N. P., Higbee, D., Ablonczy, Z., Crouch, R. K., & Koutalos, Y. (2012) · Investigative Ophthalmology & Visual Science · Cited by 1 · see citing works
Self-citation
Flagged first, then by citations
3 of the 59 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Functions, Therapeutic Applications, and Synthesis of Retinoids and Carotenoids
Álvarez, R., Vaz, B., Gronemeyer, H., & de Lera, Á. R. (2014) · Chemical Reviews · doi:10.1021/cr400126u · Cited by 260 · see citing works
Molday, R. S., & Moritz, O. L. (2015) · Journal of Cell Science · doi:10.1242/jcs.175687 · Cited by 235 · see citing works
Senescence in the pathogenesis of age-related macular degeneration
Blasiak, J. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-019-03420-x · Cited by 183 · see citing works
Quantitative Fundus Autofluorescence in Healthy Eyes
Greenberg, J. P., Duncker, T., Woods, R. L., Smith, R. T., Sparrow, J. R., & Delori, F. C. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-12445 · Cited by 168 · see citing works
Lenis, T. L., Hu, J., Ng, S. Y., Jiang, Z., Sarfare, S., Lloyd, M. B., Esposito, N. J., Samuel, W., Jaworski, C., Bok, D., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1802519115 · Cited by 158 · see citing works
Mammalian P4-ATPases and ABC transporters and their role in phospholipid transport
Coleman, J. A., Quazi, F., & Molday, R. S. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2012.10.006 · Cited by 154 · see citing works
Ablonczy, Z., Higbee, D., Anderson, D. M., Dahrouj, M., Grey, A. C., Gutierrez, D. B., Koutalos, Y., Schey, K. L., Hanneken, A. M., & Crouch, R. K. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-12250 · Cited by 146 · see citing works
Self-citationQuazi, F., & Molday, R. S. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1400780111 · Cited by 129 · see citing works
Issa, P. C., Barnard, A. R., Singh, M. S., Carter, E., Jiang, Z., Radu, R. A., Schraermeyer, U., & MacLaren, R. E. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-11688 · Cited by 128 · see citing works
New insights into retinoid metabolism and cycling within the retina
Tang, P. H., Kono, M., Koutalos, Y., Ablonczy, Z., & Crouch, R. K. (2013) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2012.09.002 · Cited by 122 · see citing works
“A2E formation from 11-cis retinal While it is clear that retinoids are involved in lipofuscin, recent evidence shows 11-cis retinal itself may be a major source of lipofuscin andA2E (Boyer et al., 2012).”
Self-citationPhotodegradation of retinal bisretinoids in mouse models and implications for macular degeneration
Ueda, K., Zhao, J., Kim, H. J., & Sparrow, J. R. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1524774113 · Cited by 115 · see citing works
Structure and function of ABCA4 and its role in the visual cycle and Stargardt macular degeneration
Molday, R. S., Garces, F. A., Scortecci, J. F., & Molday, L. L. (2022) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2021.101036 · Cited by 107 · see citing works
High Resolution MALDI Imaging Mass Spectrometry of Retinal Tissue Lipids
Anderson, D. M., Ablonczy, Z., Koutalos, Y., Spraggins, J. M., Crouch, R. K., Caprioli, R. M., & Schey, K. L. (2014) · Journal of the American Society for Mass Spectrometry · doi:10.1007/s13361-014-0883-2 · Cited by 106 · see citing works
Self-citationLipofuscin causes atypical necroptosis through lysosomal membrane permeabilization
Pan, C., Banerjee, K., Lehmann, G. L., Almeida, D., Hajjar, K. A., Benedicto, I., Jiang, Z., Radu, R. A., Thompson, D. H., Rodriguez-Boulan, E. J., et al. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2100122118 · Cited by 94 · see citing works
Dobri, N., Qin, Q., Kong, J., Yamamoto, K., Liu, Z., Moiseyev, G., Ma, J.-X., Allikmets, R., Sparrow, J. R., & Petrukhin, K. (2013) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.12-10050 · Cited by 91 · see citing works
Retina, retinol, retinal and the natural history of vitamin A as a light sensor
Zhong, M., Kawaguchi, R., Kassai, M., & Sun, H. (2012) · Nutrients · doi:10.3390/nu4122069 · Cited by 89 · see citing works
Fundus Autofluorescence and RPE Lipofuscin in Age-Related Macular Degeneration
Sparrow, J. R., & Duncker, T. (2014) · Journal of Clinical Medicine · doi:10.3390/jcm3041302 · Cited by 89 · see citing works
Bermond, K., Wobbe, C., Tarau, I., Heintzmann, R., Hillenkamp, J., Curcio, C. A., Sloan, K. R., & Ach, T. (2020) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.61.5.35 · Cited by 85 · see citing works
Fronk, A., & Vargis, E. (2016) · Journal of Tissue Engineering · doi:10.1177/2041731416650838 · Cited by 81 · see citing works
Visual Cycle Modulation as an Approach toward Preservation of Retinal Integrity
Båvik, C., Henry, S., Zhang, Y., Mitts, K., McGinn, T. E., Budzynski, E., Pashko, A., Lieu, K. L., Zhong, S., Blumberg, B., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0124940 · Cited by 75 · see citing works
Hyttinen, J. M. T., Błasiak, J., Niittykoski, M., Kinnunen, K., Kauppinen, A., Salminen, A., & Kaarniranta, K. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.03.006 · Cited by 71 · see citing works
Molday, R. S. (2015) · Progress in Molecular Biology and Translational Science · doi:10.1016/bs.pmbts.2015.06.008 · Cited by 70 · see citing works
Sears, A. E., Bernstein, P. S., Cideciyan, A. V., Hoyng, C. B., Issa, P. C., Palczewski, K., Rosenfeld, P. J., Sadda, S. R., Schraermeyer, U., Sparrow, J. R., et al. (2017) · Translational Vision Science & Technology · doi:10.1167/tvst.6.5.6 · Cited by 69 · see citing works
Garces, F. A., Jiang, K., Molday, L. L., Stöhr, H., Weber, B. H. F., Lyons, C. J., Maberley, D., & Molday, R. S. (2018) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.17-23364 · Cited by 68 · see citing works
Chemistry and Biology of the Initial Steps in Vision: The Friedenwald Lecture
Palczewski, K. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-15502 · Cited by 68 · see citing works
Sharma, R., Williams, D. R., Palczewska, G., Palczewski, K., & Hunter, J. J. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-17961 · Cited by 67 · see citing works
Meleppat, R. K., Ronning, K. E., Karlen, S. J., Burns, M. E., Pugh, E. N., & Zawadzki, R. J. (2021) · Scientific Reports · doi:10.1038/s41598-021-95320-z · Cited by 63 · see citing works
Review of clinical approaches in fluorescence lifetime imaging ophthalmoscopy
Sauer, L., Andersen, K. M., Dysli, C., Zinkernagel, M. S., Bernstein, P. S., & Hammer, M. (2018) · Journal of Biomedical Optics · doi:10.1117/1.jbo.23.9.091415 · Cited by 61 · see citing works
Rôżanowska, M. (2023) · Antioxidants · doi:10.3390/antiox12122111 · Cited by 59 · see citing works
Stargardt macular dystrophy and evolving therapies
Hussain, R. M., Ciulla, T. A., Berrocal, A. M., Gregori, N. Z., Flynn, H. W., & Lam, B. L. (2018) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2018.1513486 · Cited by 56 · see citing works
Crouch, R. K., Koutalos, Y., Kono, M., Schey, K. L., & Ablonczy, Z. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.06.005 · Cited by 53 · see citing works
Self-citationOxidative Stress and Inflammation in Retinal Degeneration
Jadeja, R. N., & Martin, P. M. (2021) · Antioxidants · doi:10.3390/antiox10050790 · Cited by 50 · see citing works
Fundus Autofluorescence and Clinical Applications
Pole, C., & Ameri, H. (2021) · Journal of Ophthalmic and Vision Research · doi:10.18502/jovr.v16i3.9439 · Cited by 49 · see citing works
Light Damage in Abca4 and Rpe65 rd12 Mice
Wu, L., Ueda, K., Nagasaki, T., & Sparrow, J. R. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-13867 · Cited by 48 · see citing works
Molday, L. L., Wahl, D. J., Šarunic, M. V., & Molday, R. S. (2017) · Human Molecular Genetics · doi:10.1093/hmg/ddx400 · Cited by 48 · see citing works
Photoreceptor cells as a source of fundus autofluorescence in recessive Stargardt disease
Paavo, M., Lee, W., Allikmets, R. L., Tsang, S. H., & Sparrow, J. R. (2018) · Journal of Neuroscience Research · doi:10.1002/jnr.24252 · Cited by 46 · see citing works
Rôżanowska, M. (2012) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2012.01240.x · Cited by 45 · see citing works
Phospholipid scrambling by rhodopsin
Ernst, O. P., & Menon, A. K. (2015) · Photochemical & Photobiological Sciences · doi:10.1039/c5pp00195a · Cited by 41 · see citing works
Fluorescence lifetime imaging ophthalmoscopy: autofluorescence imaging and beyond
Sauer, L., Vitale, A. S., Modersitzki, N. K., & Bernstein, P. S. (2020) · Eye · doi:10.1038/s41433-020-01287-y · Cited by 41 · see citing works
Donato, L., Scimone, C., Alibrandi, S., Scalinci, S. Z., Rinaldi, C., D’Angelo, R., & Sidoti, A. (2022) · Antioxidants · doi:10.3390/antiox11101967 · Cited by 40 · see citing works
A reciprocating twin-channel model for ABC transporters
Jones, P. M., & George, A. M. (2014) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583514000031 · Cited by 40 · see citing works
Rácz, B., Váradi, A., Kong, J., Allikmets, R. L., Pearson, P. G., Johnson, G., Cioffi, C. L., & Petrukhin, K. E. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.002062 · Cited by 40 · see citing works
Vitamin A-aldehyde adducts: AMD risk and targeted therapeutics
Sparrow, J. R. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1600474113 · Cited by 39 · see citing works
Saito, Y., Yako, T., Otsu, W., Nakamura, S., Inoue, Y., Muramatsu, A., Nakagami, Y., Shimazawa, M., & Hara, H. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.03.012 · Cited by 39 · see citing works
Curtis, S. B., Molday, L. L., Garces, F. A., & Molday, R. S. (2020) · Human Mutation · doi:10.1002/humu.24100 · Cited by 39 · see citing works
Cell-autonomous lipid-handling defects in Stargardt iPSC-derived retinal pigment epithelium cells
Farnoodian, M., Bose, D., Khristov, V., Susaimanickam, P. J., Maddileti, S., Mariappan, I., Abu-Asab, M. S., Campos, M. M., Villasmil, R., Wan, Q., et al. (2022) · Stem Cell Reports · doi:10.1016/j.stemcr.2022.10.001 · Cited by 38 · see citing works
Petrukhin, K. E. (2013) · Drug Discovery Today Therapeutic Strategies · doi:10.1016/j.ddstr.2013.05.004 · Cited by 37 · see citing works
Ablonczy, Z., Higbee, D., Grey, A. C., Koutalos, Y., Schey, K. L., & Crouch, R. K. (2013) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2013.08.005 · Cited by 36 · see citing works
Self-citationLee, M., Li, S., Sato, K., & Jin, M. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-18551 · Cited by 36 · see citing works
Endogenous Fluorophores Enable Two-Photon Imaging of the Primate Eye
Palczewska, G., Golczak, M., Williams, D. R., Hunter, J. J., & Palczewski, K. (2014) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.14-14395 · Cited by 33 · see citing works
Functional Characterization of ABCA4 Missense Variants Linked to Stargardt Macular Degeneration
Garces, F. A., Scortecci, J. F., & Molday, R. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms22010185 · Cited by 32 · see citing works
The physiology of the retinal pigment epithelium in Danon disease
Thompson, D. A., Constable, P. A., Liasis, A., Walters, B., & Esteban, M. T. (2016) · Retina · doi:10.1097/iae.0000000000000736 · Cited by 31 · see citing works
Meleppat, R. K., Ronning, K. E., Karlen, S. J., Kothandath, K. K., Burns, M. E., Pugh, E. N., & Zawadzki, R. J. (2020) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.61.13.1 · Cited by 31 · see citing works
Ross, A., & Harrison, E. H. (2013) · CRC Press eBooks · doi:10.1201/b15413-2 · Cited by 30 · see citing works
Ablonczy, Z., Smith, N., Anderson, D. M., Grey, A. C., Spraggins, J. M., Koutalos, Y., Schey, K. L., & Crouch, R. K. (2014) · PROTEOMICS · doi:10.1002/pmic.201300406 · Cited by 29 · see citing works
Self-citationPotential Therapeutic Agents Against Retinal Diseases Caused by Aberrant Metabolism of Retinoids
Liu, X., Chen, J., Liu, Z., Li, J., Yao, K., & Wu, Y. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.15-18429 · Cited by 29 · see citing works
Forrester, J. V., Dick, A. D., McMenamin, P. G., Roberts, F., & Pearlman, E. M. (2015) · Elsevier eBooks · doi:10.1016/b978-0-7020-5554-6.00004-6 · Cited by 29 · see citing works
Adler, L., Boyer, N. P., Anderson, D. M., Spraggins, J. M., Schey, K. L., Hanneken, A. M., Ablonczy, Z., Crouch, R. K., & Koutalos, Y. (2015) · Photochemical & Photobiological Sciences · doi:10.1039/c5pp00156k · Cited by 28 · see citing works
Self-citationA2E and lipofuscin distributions in macaque retinal pigment epithelium are similar to human
Pallitto, P. M., Ablonczy, Z., Jones, E. E., Drake, R. R., Koutalos, Y., Crouch, R. K., Donello, J. E., & Herrmann, J. E. (2015) · Photochemical & Photobiological Sciences · doi:10.1039/c5pp00170f · Cited by 27 · see citing works
Self-citationBowrey, H. E., Anderson, D. M., Pallitto, P. M., Gutierrez, D. B., Fan, J., Crouch, R. K., Schey, K. L., & Ablonczy, Z. (2015) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201500103 · Cited by 27 · see citing works
Self-citationRegulation of oxidative stress and inflammatory responses in human retinal pigment epithelial cells
Bhattarai, N. (2022) · Acta Ophthalmologica · doi:10.1111/aos.15275 · Cited by 27 · see citing works
Multiple A2E treatments lead to melanization of rod outer segment-challenged ARPE-19 cells.
Poliakov, E., Strunnikova, N. V., Jiang, J., Martinez, B., Parikh, T. P., Lakkaraju, A., Thomas, C. J., Brooks, B. P., & Redmond, T. M. (2014) · Europe PMC (PubMed Central) · Cited by 27 · see citing works
Ward, R. H. R., Kaylor, J. J., Cobice, D., Pepe, D. A., McGarrigle, E. M., Brockerhoff, S. E., Hurley, J. B., Travis, G. H., & Kennedy, B. N. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.011374 · Cited by 25 · see citing works
Targeting Inflammation in Emerging Therapies for Genetic Retinal Disease
viringipurampeer, I. A., Bashar, E., Gregory, C. Y., Moritz, O. L., & Gregory-Evans, K. (2013) · International Journal of Inflammation · doi:10.1155/2013/581751 · Cited by 25 · see citing works
Chen, C., Adler, L., Goletz, P. W., Gonzalez-Fernandez, F., Thompson, D. A., & Koutalos, Y. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m117.795187 · Cited by 24 · see citing works
Self-citationVitamin A, systemic T-cells, and the eye: Focus on degenerative retinal disease
Thirunavukarasu, A. J., Ross, A. C., & Gilbert, R. M. (2022) · Frontiers in Nutrition · doi:10.3389/fnut.2022.914457 · Cited by 26 · see citing works
Zhao, J., Ueda, K., Riera, M., Kim, H. J., & Sparrow, J. R. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.005949 · Cited by 24 · see citing works
Tisi, A., Parete, G., Flati, V., & Maccarone, R. (2020) · Scientific Reports · doi:10.1038/s41598-020-63449-y · Cited by 24 · see citing works
Lack of Acid Sphingomyelinase Induces Age-Related Retinal Degeneration
Wu, B. X., Fan, J., Boyer, N. P., Jenkins, R. W., Koutalos, Y., Hannun, Y. A., & Crosson, C. E. (2015) · PLoS ONE · doi:10.1371/journal.pone.0133032 · Cited by 23 · see citing works
Self-citationRetina and RPE lipid profile changes linked with ABCA4 associated Stargardt's maculopathy
Farnoodian, M., Bose, D., Barone, F., Nelson, L. M., Boyle, M. P., Jun, B., Do, K., Gordon, W. C., Kautzmann, M.-A. I., Perera, R. M., et al. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108482 · Cited by 22 · see citing works
Pham, T. N. M., Shin, C.-Y., Park, S. H., Lee, T. H., Ryu, H. Y., Kim, S., Auh, K., & Jeong, K. W. (2021) · Nutrients · doi:10.3390/nu13020359 · Cited by 22 · see citing works
Polyunsaturated Lipids in the Light-Exposed and Prooxidant Retinal Environment
Longoni, B., & Demontis, G. C. (2023) · Antioxidants · doi:10.3390/antiox12030617 · Cited by 21 · see citing works
Li, J., Yao, K., Yu, X., Dong, X., Gan, L., Luo, C., & Wu, Y. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.511386 · Cited by 21 · see citing works
The 11-cis Retinal Origins of Lipofuscin in the Retina
Adler, L., Boyer, N. P., Chen, C., Ablonczy, Z., Crouch, R. K., & Koutalos, Y. (2015) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2015.07.022 · Cited by 21 · see citing works
Self-citationZhao, J., Liao, Y., Chen, J., Dong, X., Gao, Z., Zhang, H., Wu, X., Liu, Z., & Wu, Y. (2017) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-20734 · Cited by 21 · see citing works
A novel RPE65 inhibitor CU239 suppresses visual cycle and prevents retinal degeneration
Shin, Y., Moiseyev, G. P., Petrukhin, K. E., Cioffi, C. L., Muthuraman, P., Takahashi, Y., & Ma, J. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.04.014 · Cited by 21 · see citing works
Biswas, E. E., Affet, S., Ha, M., & Biswas, S. B. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.409623 · Cited by 21 · see citing works
The effect of a chrysanthemum water extract in protecting the retina of mice from light damage
Gong, Y., Wang, X., Wang, Y., Hao, P., Wang, H., Guo, Y., & Zhang, W. (2022) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-022-03701-2 · Cited by 19 · see citing works
Kolesnikov, A. V., Maeda, A., Tang, P. H., Imanishi, Y., Palczewski, K., & Kefalov, V. J. (2015) · The Journal of Physiology · doi:10.1113/jp271285 · Cited by 18 · see citing works
Xu, T., Molday, L. L., & Molday, R. S. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.104614 · Cited by 17 · see citing works
Bisretinoid Photodegradation Is Likely Not a Good Thing
Ueda, K., Kim, H. J., Zhao, J., & Sparrow, J. R. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-75402-4_49 · Cited by 16 · see citing works
Fundus autofluorescence applications in retinal imaging
Lanzetta, P., Gabai, A., & Veritti, D. (2015) · Indian Journal of Ophthalmology · doi:10.4103/0301-4738.159868 · Cited by 16 · see citing works
Lee, S. J., Roh, Y. J., Kim, J. E., Jin, Y. J., Song, H. J., Seol, A., Park, S. H., Douangdeuane, B., Souliya, O., Choi, S. I., et al. (2023) · Antioxidants · doi:10.3390/antiox12020329 · Cited by 15 · see citing works
Boyer, N. P., Thompson, D. A., & Koutalos, Y. (2021) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.62.2.1 · Cited by 15 · see citing works
Self-citationLunegova, D. A., Александрович, Г. Д., Senin, I. I., Gudkova, V. R., Sidorenko, S. V., Tiulina, V. V., Shebardina, N. G., Yakovleva, M. A., Feldman, T. B., Ramonova, A. A., et al. (2024) · FEBS Journal · doi:10.1111/febs.17335 · Cited by 15 · see citing works
Retinoid analogs and polyphenols as potential therapeutics for age-related macular degeneration
Parmar, T., Ortega, J. T., & Jastrzębska, B. (2020) · Experimental Biology and Medicine · doi:10.1177/1535370220926938 · Cited by 13 · see citing works
Formation of lipofuscin-like material in the RPE Cell by different components of rod outer segments
Lei, L., Tzekov, R. T., McDowell, J. H., Smith, W. C., Tang, S., & Kaushal, S. (2013) · Experimental Eye Research · doi:10.1016/j.exer.2013.04.006 · Cited by 13 · see citing works
Fructosamine-3-Kinase as a Potential Treatment Option for Age-Related Macular Degeneration
Bruyne, S. D., den Broecke, C. V., Vrielinck, H., Khelifi, S., Wever, O. D., Bracke, K. R., Huizing, M. T., Boston, N., Himpe, J., Speeckaert, M. M., et al. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9092869 · Cited by 13 · see citing works
Wang, Y., Ma, X., Muthuraman, P., Raja, A., Jayaraman, A., Petrukhin, K. E., Cioffi, C. L., Ma, J., & Moiseyev, G. P. (2022) · PLoS ONE · doi:10.1371/journal.pone.0269437 · Cited by 12 · see citing works
Navaratnam, J., Salvanos, P., Vavvas, D. G., & Bragadóttir, R. (2020) · Acta Ophthalmologica · doi:10.1111/aos.14521 · Cited by 12 · see citing works
Herbal molecules in eye diseases
Chu, K.-O., & Pang, C. (2014) · Taiwan Journal of Ophthalmology · doi:10.1016/j.tjo.2014.03.005 · Cited by 11 · see citing works
New findings on pathogenetic mechanisms in the development of age-related macular degeneration
Фурсова, А. Ж., Derbeneva, A. S., Vasilyeva, M. A., Nikulich, I. F., Сергеевич, Т. М., Gamza, Y. A., Викторовна, Ч. Н., Gusarevich, O. G., Dmitrieva, E. I., Kozhevnikova, O. S., et al. (2022) · Russian Annals of Ophthalmology · doi:10.17116/oftalma2022138021120 · Cited by 11 · see citing works
Nociari, M., Kiss, S., & Rodriguez-Boulan, E. J. (2017) · InTech eBooks · doi:10.5772/intechopen.69304 · Cited by 11 · see citing works
Nafar, Z., Wen, R., & Jiao, S. (2018) · Biomedical Optics Express · doi:10.1364/boe.9.003768 · Cited by 10 · see citing works
Dörschmann, P., Thalenhorst, T., Seeba, C., Tischhöfer, M.-T., Neupane, S., Roider, J. B., Alban, S., & Klettner, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24097939 · Cited by 10 · see citing works
Adler, L., Chen, C., & Koutalos, Y. (2017) · Experimental Eye Research · doi:10.1016/j.exer.2017.02.007 · Cited by 10 · see citing works
Self-citationRácz, B., Váradi, A., Pearson, P. G., & Petrukhin, K. E. (2020) · PLoS ONE · doi:10.1371/journal.pone.0228291 · Cited by 9 · see citing works
Wu, Y., Jin, Q., Yao, K., Zhao, J., Chen, J., Wu, X., Gan, L., Li, J., Song, X., Liu, X., et al. (2014) · Biochemical Journal · doi:10.1042/bj20140089 · Cited by 8 · see citing works
RPE65 and the Accumulation of Retinyl Esters in Mouse Retinal Pigment Epithelium
Sheridan, C., Boyer, N. P., Crouch, R. K., & Koutalos, Y. (2017) · Photochemistry and Photobiology · doi:10.1111/php.12738 · Cited by 8 · see citing works
Self-citationBisretinoid lipofuscin, fundus autofluorescence and retinal disease
Sparrow, J. R., & Kim, H. J. (2025) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2025.101388 · Cited by 7 · see citing works
- Authors
- Boyer, N. P., Higbee, D., Currin, M. B., Blakeley, L. R., Chen, C., Ablonczy, Z., Crouch, R. K., & Koutalos, Y.
- Affiliations
- Medical University of South Carolina (US)
- Corresponding author
- Koutalos, Yiannis
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 287
- Issue
- 26
- Pages
- 22276-22286
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3381188
- OpenAlex
- W1984815704
- Cited by
- 133
- References
- 59
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 4 · 2023: 10 · 2022: 7 · 2021: 9 · 2020: 18 · 2019: 2 · 2018: 10 · 2017: 11 · 2016: 6 · 2015: 15 · 2014: 12 · 2013: 10 · 2012: 6
- FWCI
- 12.86
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1c06rr015455-01a1)
- National Eye Institute (R01EY019065, EY014850, R01EY014850, EY-014793, R24EY014793, R21EY020661, EY-004939, EY020661, R01EY004939)
- National Center for Research Resources (C06 RR-015455)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- lipofuscin, A2E, retinal pigment epithelium, rod photoreceptors, light exposure, aging, ABCA4, Stargardt disease, age-related macular degeneration, 11-cis-retinal, all-trans-retinal, rhodopsin regeneration, dark rearing
- MeSH terms
- Animals, Chromatography, High Pressure Liquid, Color, Light, Lipofuscin, Macular Degeneration, Mice, Inbred C57BL, Microscopy, Fluorescence, Models, Biological, Retina, Retinaldehyde, Retinoids, Rod Cell Outer Segment, ATP-Binding Cassette Transporters, Mice, Retinal Pigment Epithelium
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
