Restoration of Lysosomal pH in RPE Cells from Cultured Human and ABCA4 −/− Mice: Pharmacologic Approaches and Functional Recovery
Open accessAbstract
PURPOSE: Degradation of engulfed material is primarily mediated by lysosomal enzymes that function optimally within a narrow range of acidic pH values. RPE cells are responsible for daily degradation of photoreceptor outer segments and are thus particularly susceptible to perturbations in lysosomal pH. The authors hypothesized that elevated lysosomal pH levels could slow enzyme activity and encourage accumulation of partially digested material. Consequently, treatment to lower perturbed lysosomal pH levels may enhance degradative activity. METHODS: A high-throughput screening assay was developed to quantify the lysosomal pH of fresh mouse and cultured ARPE-19 cells. The effect of lysosomal pH on outer segment clearance was determined. RESULTS: Lysosomal pH is elevated in RPE cells from ABCA4 knockout mice and in cultured human ARPE-19 cells exposed to N-retinylidene-N-retinylethanolamine (A2E), tamoxifen, or chloroquine. The lysosomal pH of fresh RPE cells from ABCA4(-/-) mice and of chemically compromised RPE cells was reacidified by elevating intracellular cAMP directly. Compromised lysosomal pH was also restored by stimulating A(2A) adenosine or beta-adrenergic receptors, consistent with G(s)-protein coupling of these receptors. Restoring lysosomal pH with these treatments enhanced photoreceptor outer segment clearance, demonstrating functional relevance consistent with an enhancement of degradative enzyme activity. CONCLUSIONS: Elevation of lysosomal pH in RPE cells interferes with the degradation of outer segments and may contribute to the pathologies associated with A2E. Pharmacologic elevation of cAMP can restore an acid pH and improve degradative function.
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Pharmacological re-acidification of ARPE-19 cells, pretreated with lysosomal alkalinizing agents, increases their ability to degrade OS by reestablishing an acidic lysosomal environment more conducive to efficient protease activity.
“Furthermore, pharmacological re-acidification of ARPE-19 cells, pretreated with lysosomal alkalinizing agents, increases their ability to degrade OS by reestablishing an acidic lysosomal environment more conducive to efficient protease activity (Liu et al., 2008).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Liu et al., 2008
These authors also demonstrate lysosome alkalinization in the albino Abca4−/− mouse and have recently shown that restoration of lysosomal pH with P2Y12 receptor antagonist prevents photoreceptor loss in these mice.
“Moreover, these authors also demonstrate lysosome alkalinization in the albino Abca4−/− mouse (Liu et al., 2008) and have recently shown that restoration of lysosomal pH with P2Y12 receptor antagonist prevents photoreceptor loss in these mice (Lu et al., 2019).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Liu et al., 2008
Lysosomes in the RPE participate in calcium signaling and membrane repair in addition to their degradative functions, and these mechanisms are critical for maintaining RPE health and integrity.
“lysosomes in the RPE perform various roles; in addition to their degradative functions, they participate in calcium signaling and membrane repair - mechanisms that are critical for maintaining RPE health and integrity (Liu et al., 2008; Tan et al., 2016).”
From The cell biology of the retinal pigment epithelium (2020) · cites this paper as Liu et al., 2008
Cites
Nomenclature and classification of purinoceptors.
Fredholm, B. B., Abbracchio, M. P., Burnstock, G., Daly, J. W., Harden, T. K., Jacobson, K. A., Leff, P., & Williams, M. (1994) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06782-1 · Cited by 1,585 · see citing works
González‐Noriega, A., Grubb, J. H., Talkad, V. D., & Sly, W. S. (1980) · The Journal of Cell Biology · doi:10.1083/jcb.85.3.839 · Cited by 736 · see citing works
Basic Guide to the Mechanisms of Antiestrogen Action
MacGregor, J. I., & Jordan, V. C. (1998) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01358-9 · Cited by 697 · see citing works
Proteinases in Mammalian Cells and Tissues
Barrett, A. J. (1977) · Medical Entomology and Zoology · Cited by 524 · see citing works
CFTR regulates phagosome acidification in macrophages and alters bactericidal activity
Di, A., Brown, M. E., Deriy, L. V., Li, C., Szeto, F. L., Chen, Y., Huang, P. C., Tong, J., Naren, A. P., Bindokas, V. P., et al. (2006) · Nature Cell Biology · doi:10.1038/ncb1456 · Cited by 494 · 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
Finnemann, S. C., Bonilha, V. L., Marmorstein, A. D., & Rodriguez-Boulan, E. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.12932 · Cited by 382 · see citing works
Lien, E. A., Solheim, E., & Ueland, P. M. (1991) · PubMed · Cited by 362 · see citing works
Chaperone-mediated autophagy in aging and disease
Massey, A. C., Zhang, C., & Cuervo, A. M. (2006) · Current Topics in Developmental Biology · doi:10.1016/s0070-2153(05)73007-6 · Cited by 315 · 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
Involvement of oxidative mechanisms in blue-light-induced damage to A2E-laden RPE.
Sparrow, J. R., Zhou, J., Ben‐Shabat, S., Vollmer-Snarr, H. R., Itagaki, Y., & Nakanishi, K. (2002) · PubMed · Cited by 284 · see citing works
Finnemann, S. C., Leung, L. W., & Rodriguez-Boulan, E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052025899 · Cited by 283 · see citing works
Inhibition of lysosomal degradative functions in RPE cells by a retinoid component of lipofuscin.
Holz, F. G., Schütt, F., Kopitz, J., Eldred, G. E., Kruse, F. E., Völcker, H. E., & Cantz, M. (1999) · PubMed · Cited by 280 · see citing works
Schneider, D. L. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)69536-0 · Cited by 251 · see citing works
Bergmann, M., Schütt, F., Holz, F. G., & Kopitz, J. (2004) · The FASEB Journal · doi:10.1096/fj.03-0289fje · Cited by 226 · see citing works
Pastor‐Soler, N. M., Beaulieu, V., Litvin, T. N., Silva, N. D., Chen, Y., Brown, D., Buck, J., Levin, L. R., & Breton, S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m309543200 · Cited by 225 · see citing works
Cuervo, A. M., & Dice, J. F. (2000) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00075-9 · Cited by 215 · see citing works
Bioenergetics of secretory vesicles
Njus, D., Kelley, P. M., & Harnadek, G. J. (1986) · Biochimica et Biophysica Acta (BBA) - Reviews on Bioenergetics · doi:10.1016/0304-4173(87)90003-6 · Cited by 209 · see citing works
Geisow, M. J., & Evans, W. H. (1984) · Experimental Cell Research · doi:10.1016/0014-4827(84)90699-2 · Cited by 180 · see citing works
The lipofuscin fluorophore A2E perturbs cholesterol metabolism in retinal pigment epithelial cells
Lakkaraju, A., Finnemann, S. C., & Rodriguez-Boulan, E. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702504104 · Cited by 162 · see citing works
Fluorescein conjugates as indicators of subcellular pH
Geisow, M. J. (1984) · Experimental Cell Research · doi:10.1016/0014-4827(84)90698-0 · Cited by 144 · see citing works
The ClC-3 chloride channel promotes acidification of lysosomes in CHO-K1 and Huh-7 cells
Li, X., Wang, T., Zhao, Z., & Weinman, S. A. (2002) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00504.2001 · Cited by 140 · see citing works
Vesicular Anthracycline Accumulation in Doxorubicin-Selected U-937 Cells: Participation of Lysosomes
Hurwitz, S. J., Terashima, M., Mizunuma, N., & Slapak, C. A. (1997) · Blood · doi:10.1182/blood.v89.10.3745 · Cited by 137 · see citing works
Inhibition of RPE lysosomal and antioxidant activity by the age pigment lipofuscin.
Shamsi, F. A., & Boulton, M. (2001) · PubMed · Cited by 130 · see citing works
Ocular toxicity in low-dose tamoxifen: A prospective study
Noureddin, B. N., Seoud, M., Bashshur, Z. F., Salem, Z. M. K., Shamseddin, A., & Khalil, A. (1999) · Eye · doi:10.1038/eye.1999.217 · Cited by 130 · see citing works
Rod outer segment disc shedding in relation to cyclic lighting
LaVail, M. M. (1976) · Experimental Eye Research · doi:10.1016/0014-4835(76)90209-8 · Cited by 120 · see citing works
Sun‐Wada, G., Wada, Y., & Futai, M. (2003) · Cell Structure and Function · doi:10.1247/csf.28.455 · Cited by 119 · see citing works
Use of the ARPE-19 cell line as a model of RPE polarity: basolateral secretion of FGF5.
Dunn, K. C., Marmorstein, A. D., Bonilha, V. L., Rodriguez-Boulan, E. J., Giordano, F., & Hjelmeland, L. M. (1998) · PubMed · Cited by 117 · see citing works
Tamoxifen inhibits acidification in cells independent of the estrogen receptor
Altan, N., Chen, Y., Schindler, M., & Simon, S. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.8.4432 · Cited by 113 · see citing works
Sharov, V. G., Todor, A. V., Khanal, S., Imai, M., & Sabbah, H. N. (2006) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2006.09.013 · Cited by 112 · see citing works
Release of ATP from retinal pigment epithelial cells involves both CFTR and vesicular transport
Reigada, D., & Mitchell, C. H. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00201.2004 · Cited by 108 · see citing works
Self-citationChloroquine causes lysosomal dysfunction in neural retina and RPE: implications for retinopathy
Mahon, G. J., Anderson, H. R., Gardiner, T. A., McFarlane, S., Archer, D. B., & Stitt, A. W. (2004) · Current Eye Research · doi:10.1076/ceyr.28.4.277.27835 · Cited by 108 · see citing works
The Basis of Antimalarial Action: Non-Weak Base Effects of Chloroquine on Acid Vesicle pH
Krogstad, D. J., & Schlesinger, P. H. (1987) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.1987.36.213 · Cited by 106 · see citing works
Pothos, E. N., Mosharov, E. V., Liu, K., Setlik, W., Haburčák, M., Baldini, G., Gershon, M. D., Tamir, H., & Sulzer, D. L. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2002.018630 · Cited by 102 · see citing works
Purification, characterization and molecular cloning of human hepatic lysosomal acid lipase
Ameis, D., Merkel, M., Eckerskorn, C., & Greten, H. (1994) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1994.tb18572.x · Cited by 101 · see citing works
VANLEEUWEN, R. (2004) · Ophthalmology · doi:10.1016/j.ophtha.2003.10.024 · Cited by 98 · see citing works
Intracellular Chloride Channels: Determinants of Function in the Endosomal Pathway
Faúndez, V., & Hartzell, H. C. (2004) · Science s STKE · doi:10.1126/stke.2332004re8 · Cited by 91 · see citing works
Kinetic studies of rod outer segment binding and ingestion by cultured rat RPE cells
Hall, M. O., & Abrams, T. A. (1987) · Experimental Eye Research · doi:10.1016/s0014-4835(87)80105-7 · Cited by 87 · see citing works
Eldred, G. E. (2009) · Gerontology · doi:10.1159/000213722 · Cited by 83 · see citing works
A Mechanism for Tamoxifen-mediated Inhibition of Acidification
Chen, Y., Schindler, M., & Simon, S. M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.26.18364 · Cited by 80 · see citing works
Elner, V. M. (2002) · PubMed Central · Cited by 73 · see citing works
Human trabecular meshwork cell volume regulation
Mitchell, C. H., Fleischhauer, J. C., Stamer, W. D., Peterson–Yantorno, K., & Civan, M. M. (2002) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00544.2001 · Cited by 72 · see citing works
Self-citationSchlo¨tzer-Schrehardt, U., Zenkel, M., Decking, U. K. M., Haubs, D., Kruse, F. E., Ju¨nemann, A., Coca‐Prados, M., & Naumann, G. O. H. (2005) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.04-0915 · Cited by 66 · see citing works
Retinal pigment epithelial function: a role for CFTR?
Blaug, S., Quinn, R. H., Quong, J. N., Jalickee, S., & Miller, S. S. (2003) · Documenta Ophthalmologica · doi:10.1023/a:1022514031645 · Cited by 63 · see citing works
Mitchell, C. H., & Reigada, D. (2007) · Purinergic Signalling · doi:10.1007/s11302-007-9054-2 · Cited by 59 · see citing works
Self-citationBergmann, M., Schütt, F., Holz, F. G., & Kopitz, J. (2001) · Experimental Eye Research · doi:10.1006/exer.2000.0949 · Cited by 53 · see citing works
Kennedy, C. J., Rakoczy, P. E., Robertson, T. A., Papadimitriou, J. M., & Constable, I. J. (1994) · Experimental Cell Research · doi:10.1006/excr.1994.1031 · Cited by 44 · see citing works
Reigada, D., Lu, W., & Mitchell, C. H. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.114439 · Cited by 44 · see citing works
Self-citationHall, M. O., Abrams, T. A., & Mittag, T. W. (1993) · PubMed · Cited by 41 · see citing works
Isolation and Culture of Primary Mouse Retinal Pigmented Epithelial Cells
Gibbs, D., & Williams, D. S. (2003) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-0067-4_44 · Cited by 41 · see citing works
Tamoxifen retinopathy: does it really exist?
Lazzaroni, F., Scorolli, L., Pizzoleo, C. F., Savini, G., Nigris, A. D., Giosa, F., & Meduri, R. A. (1998) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s004170050139 · Cited by 41 · see citing works
Peters, S., Reinthal, E., Blitgen-Heinecke, P., Bartz-Schmidt, K.-U., & Schraermeyer, U. (2006) · Ophthalmic Research · doi:10.1159/000090268 · Cited by 41 · see citing works
Degradation of rod outer segment proteins by cathepsin D
HAYASAKA, S., HARA, S., & MIZUNO, K. (1975) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a131034 · Cited by 34 · see citing works
Tamoxifen Induces Changes in the Lipid Composition of the Retinal Pigment Epithelium Cell Line D407
Engelke, M., Tykhonova, S., Zorn‐Kruppa, M., & Diehl, H. A. (2002) · Pharmacology & Toxicology · doi:10.1034/j.1600-0773.2002.910103.x · Cited by 32 · see citing works
Toimela, T., Tähti, H., & Salminen, L. (2009) · Ophthalmic Research · doi:10.1159/000267861 · Cited by 32 · see citing works
Toimela, T., Salminen, L., & Tähti, H. (1998) · Pharmacology & Toxicology · doi:10.1111/j.1600-0773.1998.tb01477.x · Cited by 30 · see citing works
Functional abnormalities in the retinal pigment epithelium of CFTR mutant mice
Wu, J., Marmorstein, A. D., & Peachey, N. S. (2006) · Experimental Eye Research · doi:10.1016/j.exer.2006.01.021 · Cited by 24 · see citing works
Essner, E. S., Gorrin, G. M., & Griewski, R. A. (1978) · PubMed · Cited by 22 · see citing works
Glycosidases of the retinal pigment epithelium.
Lentrichia, B. B., Bruner, W. E., & Kean, E. L. (1978) · PubMed · Cited by 21 · see citing works
Siakotos, A. N., Armstrong, D., Koppang, N., & Connole, E. (1978) · PubMed · Cited by 16 · see citing works
Dyke, R. W. V. (1997) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1997.272.4.c1123 · Cited by 9 · see citing works
Partial purification and properties of acid lipase in the bovine retinal pigment epithelium
Hayasaka, S., Hara, S., & Mizuno, K. (1977) · Experimental Eye Research · doi:10.1016/0014-4835(77)90099-9 · Cited by 6 · see citing works
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Colacurcio, D. J., & Nixon, R. A. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.05.004 · Cited by 548 · see citing works
Wan, Q., Chen, S., Shi, W. S., Li, L., & Ma, H. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201405742 · Cited by 419 · see citing works
The cell biology of the retinal pigment epithelium
Lakkaraju, A., Umapathy, A., Tan, L. X., Daniele, L., Philp, N. J., Boesze-Battaglia, K., & Williams, D. S. (2020) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2020.100846 · Cited by 422 · see citing works
Kaarniranta, K., Sinha, D., Blasiak, J., Kauppinen, A., Veréb, Z., Salminen, A., Boulton, M. E., & Petrovski, G. (2013) · Autophagy · doi:10.4161/auto.24546 · Cited by 326 · see citing works
Dry Age-Related Macular Degeneration: Mechanisms, Therapeutic Targets, and Imaging
Rickman, C. B., Farsiu, S., Toth, C. A., & Klingeborn, M. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-12757 · Cited by 285 · see citing works
Henry, A. G., Aghamohammadzadeh, S., Samaroo, H., Chen, Y., Mou, K., Needle, E., & Hirst, W. D. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv314 · Cited by 235 · see citing works
Cunha, R. A., & Agostinho, P. M. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1408 · Cited by 233 · see citing works
Yoon, Y. H., Cho, K. S., Hwang, J. J., Lee, S.-J., Choi, J. A., & Koh, J.-Y. (2010) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.10-5278 · Cited by 219 · see citing works
Coffey, E. E., Beckel, J. M., Laties, A. M., & Mitchell, C. H. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.01.001 · Cited by 183 · see citing works
Self-citationChemical screening identifies ATM as a target for alleviating senescence
Kang, H. T., Park, J. T., Choi, K., Kim, Y., Choi, H. J. C., Jung, C. W., Lee, Y.-S., & Park, S. C. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2342 · Cited by 184 · see citing works
Why Senescent Cells Are Resistant to Apoptosis: An Insight for Senolytic Development
Hu, L., Li, H., Zi, M., Li, W., Liu, J., Yang, Y., Zhou, D., Kong, Q., Zhang, Y., & He, Y. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.822816 · Cited by 167 · see citing works
Self-citationPhagocytosis by the Retinal Pigment Epithelium: Recognition, Resolution, Recycling
Kwon, W., & Freeman, S. A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.604205 · Cited by 157 · see citing works
Autophagy in the Retina: A Potential Role in Age-Related Macular Degeneration
Mitter, S. K., Rao, H. V., Qi, X., Cai, J., Sugrue, A., Dunn, W. A., Grant, M. B., & Boulton, M. E. (2012) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4614-0631-0_12 · Cited by 136 · see citing works
Functional roles of bestrophins in ocular epithelia
Marmorstein, A. D., Cross, H. E., & Peachey, N. S. (2009) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2009.04.004 · Cited by 134 · see citing works
Autophagy in the eye: implications for ocular cell health.
Frost, L. S., Mitchell, C. H., & Boesze-Battaglia, K. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2014.04.010 · Cited by 134 · see citing works
Self-citationChen, X., Ghribi, O., & Geiger, J. D. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1376 · Cited by 133 · see citing works
Baltazar, G. C., Guha, S., Lu, W., Lim, J. C.-S., Boesze‐Battaglia, K., Laties, A. M., Tyagi, P., Kompella, U. B., & Mitchell, C. H. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049635 · Cited by 133 · see citing works
Self-citationChen, P. M., Gombart, Z. J., & Chen, J. W. (2011) · Cell & Bioscience · doi:10.1186/2045-3701-1-10 · Cited by 122 · see citing works
Adjustment of the lysosomal-mitochondrial axis for control of cellular senescence
Park, J. T., Lee, Y.-S., Cho, K. A., & Park, S. C. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.08.003 · Cited by 123 · see citing works
Sanderson, J., Dartt, D. A., Trinkaus‐Randall, V., Pintor, J. J., Civan, M. M., Delamere, N. A., Fletcher, E. L., Salt, T. E., Grosche, A., & Mitchell, C. H. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2014.08.009 · Cited by 128 · see citing works
Self-citationGao, Y. J., Hu, Y., Liu, Q., Li, X., Li, X., Kim, C., James, T. D., Li, J., Chen, X., & Guo, Y. (2021) · Angewandte Chemie International Edition · doi:10.1002/anie.202101278 · Cited by 125 · see citing works
Phagocytosis-dependent ketogenesis in retinal pigment epithelium
Reyes-Reveles, J., Dhingra, A., Alexander, D., Bragin, A., Philp, N. J., & Boesze-Battaglia, K. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.770784 · Cited by 116 · see citing works
Mechanisms for Countering Oxidative Stress and Damage in Retinal Pigment Epithelium
Plafker, S. M., O'Mealey, G. B., & Szweda, L. I. (2012) · International review of cytology · doi:10.1016/b978-0-12-394309-5.00004-3 · Cited by 115 · see citing works
Modulation of deregulated chaperone-mediated autophagy by a phosphopeptide
Macri, C., Wang, F., Tasset, I., Schall, N., Pagé, N., Briand, J., Cuervo, A. M., & Muller, S. (2015) · Autophagy · doi:10.1080/15548627.2015.1017179 · Cited by 106 · see citing works
Protein Kinase A Activation Promotes Cancer Cell Resistance to Glucose Starvation and Anoikis
Palorini, R., Votta, G., Pirola, Y., Vitto, H. D., Palma, S. D., Airoldi, C., Vasso, M., Ricciardiello, F., Lombardi, P. P., Cirulli, C., et al. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1005931 · Cited by 94 · see citing works
The P2X7 Receptor in Microglial Cells Modulates the Endolysosomal Axis, Autophagy, and Phagocytosis
Campagno, K. E., & Mitchell, C. H. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.645244 · Cited by 90 · see citing works
Self-citationJaworska, A., Jamieson, L. E., Małek, K., Campbell, C. J., Choo, J., Chłopicki, S., & Barańśka, M. (2014) · The Analyst · doi:10.1039/c4an01988a · Cited by 89 · see citing works
Guha, S., Baltazar, G. C., Coffey, E. E., Tu, L., Lim, J. C.-S., Beckel, J. M., Patel, S., Eysteinsson, Þ., Lu, W., O’Brien-Jenkins, A., et al. (2013) · The FASEB Journal · doi:10.1096/fj.13-236166 · Cited by 89 · see citing works
Self-citationWan, Q., Chen, S., Shi, W. S., Li, L., & Ma, H. (2014) · Angewandte Chemie · doi:10.1002/ange.201405742 · Cited by 91 · see citing works
Tetrandrine blocks autophagic flux and induces apoptosis via energetic impairment in cancer cells
Qiu, W., Su, M., Xie, F., Ai, J., Ren, Y., Zhang, J., Guan, R., He, W., Gong, Y., & Guo, Y. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.84 · Cited by 88 · see citing works
Brandstetter, C., Mohr, L. K. M., Latz, E., Holz, F. G., & Krohne, T. U. (2015) · Journal of Molecular Medicine · doi:10.1007/s00109-015-1275-1 · Cited by 86 · see citing works
Guha, S., Coffey, E. E., Lu, W., Lim, J. C.-S., Beckel, J. M., Laties, A. M., Boesze‐Battaglia, K., & Mitchell, C. H. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2014.05.013 · Cited by 81 · see citing works
Self-citationExpression and Modulation of RPE Cell Membrane Complement Regulatory Proteins
Yang, P., Tyrrell, J., Han, I. C., & Jaffe, G. J. (2009) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.08-3202 · Cited by 77 · see citing works
Pascua‐Maestro, R., Diez‐Hermano, S., Lillo, C., Ganfornina, M. D., & Sánchez, D. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006603 · Cited by 78 · see citing works
Roosing, S., van den Born, L. I., Sangermano, R., Banfi, S., Koenekoop, R. K., Zonneveld-Vrieling, M. N., Klaver, C. C. W., van Lith-Verhoeven, J. J. C., Cremers, F. P. M., den Hollander, A. I., et al. (2014) · Ophthalmology · doi:10.1016/j.ophtha.2014.07.040 · Cited by 77 · see citing works
Zhang, C., Yan, J., Xiao, Y., Shen, Y., Wang, J., Ge, W., & Chen, Y. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18010157 · Cited by 76 · see citing works
Wang, Z., Zhang, J., Wang, Y., Xing, R., Yi, C., Zhu, H., Chen, X., Guo, J., Guo, W., Li, W., et al. (2012) · Carcinogenesis · doi:10.1093/carcin/bgs295 · Cited by 71 · see citing works
Cholesterol Trafficking: An Emerging Therapeutic Target for Angiogenesis and Cancer
Lyu, J., Yang, E. J., & Shim, J. S. (2019) · Cells · doi:10.3390/cells8050389 · Cited by 69 · see citing works
Adenosine A2A receptor as potential therapeutic target in neuropsychiatric disorders
Domenici, M. R., Ferrante, A., Martire, A., Chiodi, V., Pepponi, R., Tebano, M. T., & Popoli, P. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104338 · Cited by 70 · see citing works
Cell Senescence, Multiple Organelle Dysfunction and Atherosclerosis
Machado-Oliveira, G., Ramos, C., Marques, A. R. A., & Vieira, O. V. (2020) · Cells · doi:10.3390/cells9102146 · Cited by 66 · see citing works
Frost, L. S., Lopes, V. S., Bragin, A., Reyes-Reveles, J., Brancato, J., Cohen, A., Mitchell, C. H., Williams, D. S., & Boesze-Battaglia, K. (2015) · Molecular Neurobiology · doi:10.1007/s12035-014-8920-5 · Cited by 63 · see citing works
Self-citationGuha, S., Liu, J., Baltazar, G., Laties, A. M., & Mitchell, C. H. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-3209-8_14 · Cited by 62 · see citing works
Self-citationStrunnikova, N., Barb, J. J., Sergeev, Y. V., Thiagarajasubramanian, A. K., Silvin, C. J., Munson, P. J., & MacDonald, I. M. (2009) · PLoS ONE · doi:10.1371/journal.pone.0008402 · Cited by 61 · see citing works
Modulating lysosomal pH: a molecular and nanoscale materials design perspective
Zeng, J., Shirihai, O. S., & Grinstaff, M. W. (2020) · JoLS Journal of Life Sciences · doi:10.36069/jols/20201204 · Cited by 60 · see citing works
The lysosomal storage disease continuum with ageing-related neurodegenerative disease
Lloyd‐Evans, E., & Haslett, L. J. (2016) · Ageing Research Reviews · doi:10.1016/j.arr.2016.07.005 · Cited by 57 · see citing works
pH sensing via bicarbonate-regulated “soluble” adenylyl cyclase (sAC)
Rahman, N., Buck, J., & Levin, L. R. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00343 · Cited by 51 · see citing works
Liu, J., Lu, W., Guha, S., Baltazar, G. C., Coffey, E. E., Laties, A. M., Rubenstein, R. C., Reenstra, W. W., & Mitchell, C. H. (2012) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00278.2011 · Cited by 51 · see citing works
Self-citationBeckel, J. M., Gómez, N. M., Lu, W., Campagno, K. E., Nabet, B., Albalawi, F., Lim, J. C.-S., Boesze‐Battaglia, K., & Mitchell, C. H. (2018) · Scientific Reports · doi:10.1038/s41598-018-23877-3 · Cited by 51 · see citing works
Self-citationTaubitz, T., Tschulakow, A., Валерьевна, Т. М., Illing, B., Fang, Y., Biesemeier, A., Julien, S., & Schraermeyer, U. (2018) · PeerJ · doi:10.7717/peerj.5215 · Cited by 51 · see citing works
Gómez, N. M., Lu, W., Lim, J. C.-S., Kiselyov, K. I., Campagno, K. E., Grishchuk, Y., Slaugenhaupt, S. A., Pfeffer, B. A., Fliesler, S. J., & Mitchell, C. H. (2017) · The FASEB Journal · doi:10.1096/fj.201700220rr · Cited by 50 · see citing works
Self-citationBisretinoid phospholipid and vitamin A aldehyde: shining a light
Kim, H. J., & Sparrow, J. R. (2020) · Journal of Lipid Research · doi:10.1194/jlr.tr120000742 · Cited by 46 · see citing works
Zhang, K. R., Jankowski, C. S. R., Marshall, R. F., Nair, R. M., Gómez, N. M., Alnemri, A. G., Liu, Y., Erler, E. A., Ferrante, J. R., Song, Y., et al. (2023) · Disease Models & Mechanisms · doi:10.1242/dmm.050066 · Cited by 44 · see citing works
Self-citationGuha, S., Baltazar, G. C., Tu, L., Liu, J., Lim, J. C.-S., Lu, W., Argall, A. J., Boesze‐Battaglia, K., Laties, A. M., & Mitchell, C. H. (2012) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2012.07804.x · Cited by 41 · see citing works
Self-citationLei, L., Tzekov, R. T., Li, H., McDowell, J. H., Gao, G., Smith, W. C., Tang, S., & Kaushal, S. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18040728 · Cited by 41 · see citing works
Visentin, S., Nuccio, C. D., Bernardo, A., Pepponi, R., Ferrante, A., Minghetti, L., & Popoli, P. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0558-13.2013 · Cited by 40 · see citing works
Seo, B.-R., Lee, S.-J., Cho, K. S., Yoon, Y. H., & Koh, J. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.09.006 · Cited by 41 · see citing works
Soluble adenylyl cyclase is essential for proper lysosomal acidification
Rahman, N., Ramos-Espiritu, L. S., Milner, T. A., Buck, J., & Levin, L. R. (2016) · The Journal of General Physiology · doi:10.1085/jgp.201611606 · Cited by 40 · see citing works
Lee, J., Wolfe, D. M., Darji, S., McBrayer, M. K., Colacurcio, D. J., Kumar, A. R., Stavrides, P. H., Mohan, P. S., & Nixon, R. A. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.02.021 · Cited by 40 · 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
Pharmacology of the retinal pigment epithelium, the interface between retina and body system
Strauß, O. (2016) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2016.03.066 · Cited by 37 · see citing works
ATP and Adenosine in the Retina and Retinal Diseases
Ye, S.-S., Tang, Y., & Song, J. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.654445 · Cited by 37 · see citing works
Mutation-Dependent Pathomechanisms Determine the Phenotype in the Bestrophinopathies
Nachtigal, A.-L., Milenkovic, A., Brandl, C., Schulz, H. L., Duerr, L. M. J., Lang, G. E., Reiff, C., Herrmann, P., Kellner, U., & Weber, B. H. F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051597 · Cited by 34 · see citing works
Cheng, Y.-S., Linetsky, M. D., Gu, X., Ayyash, N., Gardella, A., & Salomon, R. G. (2018) · Experimental Eye Research · doi:10.1016/j.exer.2018.09.012 · Cited by 33 · 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
Retinal Pigment Epithelium Under Oxidative Stress: Chaperoning Autophagy and Beyond
Markitantova, Y. V., & Simirskii, V. N. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26031193 · Cited by 32 · see citing works
Xu, S., Liu, J., Li, D., Wang, L., Guo, J., Wang, C., & Chen, C. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.10.081 · Cited by 31 · see citing works
Self-citationKim, H. J., & Sparrow, J. R. (2018) · Journal of Lipid Research · doi:10.1194/jlr.m084459 · Cited by 31 · see citing works
Loo, T. M., Zhou, X., Tanaka, Y., Sugawara, S., Yamauchi, S., Kawasaki, H., Matsuoka, Y., Sugiura, Y., Sakuma, S., Yamanishi, Y., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-61894-9 · Cited by 31 · see citing works
Ferrante, A., Nuccio, C. D., Pepponi, R., Visentin, S., Martire, A., Bernardo, A., Minghetti, L., & Popoli, P. (2016) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.11.022 · Cited by 31 · see citing works
Antiretroviral Drugs Promote Amyloidogenesis by De-Acidifying Endolysosomes
Liang, H., Ye, Y., Soliman, M. L., Lakpa, K. L., Miller, N., Afghah, Z., Geiger, J. D., & Chen, X. (2019) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-019-09862-1 · Cited by 30 · see citing works
Markitantova, Y. V., & Simirskii, V. N. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310776 · Cited by 29 · see citing works
Early Detection of Macular Changes With Multifocal ERG in Patients on Antimalarial Drug Therapy
Nebbioso, M., Grenga, R., & Karavitis, P. (2009) · Journal of Ocular Pharmacology and Therapeutics · doi:10.1089/jop.2008.0106 · Cited by 29 · see citing works
Ferrante, A., Pèzzola, A., Matteucci, A., Biase, A. D., Attorri, L., Armida, M., Martire, A., Chern, Y., & Popoli, P. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.10.013 · Cited by 28 · see citing works
SERS nanosensors that report pH of endocytic compartments during FcεRI transit
Nowak-Lovato, K. L., Wilson, B. S., & Rector, K. D. (2010) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-010-4176-8 · 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
Tien, P., Lin, H., Tsai, Y., Lim, Y.-P., Chen, C. S., Chang, C., Lin, C.-J., Chen, J. J.-Y., Wu, S., Huang, Y.-J., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-72600-8 · Cited by 24 · see citing works
Medical bioremediation of age-related diseases
Mathieu, J. M., Schloendorn, J., Rittmann, B. E., & Alvarez, P. J. J. (2009) · Microbial Cell Factories · doi:10.1186/1475-2859-8-21 · Cited by 25 · see citing works
The Role of Bcl-x L in Mouse RPE Cell Survival
Medearis, S. A., Han, I. C., Huang, J. K., Yang, P., & Jaffe, G. J. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.10-6772 · Cited by 23 · see citing works
Impaired Lysosome Reformation in Chloroquine-Treated Retinal Pigment Epithelial Cells
Cardoso, H., Hall, M. J., Burgoyne, T., Fale, P. L. V., Storm, T., Escrevente, C., Antas, P., Seabra, M. C., & Futter, C. E. (2023) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.64.11.10 · Cited by 23 · see citing works
Effects of silica nanoparticles on endolysosome function in primary cultured neurons
Ye, Y., Liang, H., Lakpa, K. L., Xing, Y., Wollenzien, H., Chen, X., Zhao, J. X., & Geiger, J. D. (2018) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2018-0401 · Cited by 23 · see citing works
Fontaine, V. K., Monteiro, E., Brazhnikova, E., Lesage, L., Balducci, C., Guibout, L., Feraille, L., Elena, P.-P., Sahel, J., Veillet, S., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0167793 · Cited by 23 · see citing works
Espinosa, A. M. D., Link, P. A., Sicard, D., Jorba, I., Tschumperlin, D. J., & Haak, A. J. (2020) · Journal of Cell Science · doi:10.1242/jcs.248278 · Cited by 22 · see citing works
Jin, H. L., Lee, S., Kwon, Y. S., Choung, S., & Jeong, K. W. (2015) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2015.10.010 · Cited by 20 · see citing works
Kim, M. J., Kim, D. H., Kwak, H. S., Yu, I.-S., & Um, M. Y. (2022) · Antioxidants · doi:10.3390/antiox11040669 · Cited by 20 · see citing works
Lu, W., Gómez, N. M., Lim, J. C.-S., Guha, S., O’Brien-Jenkins, A., Coffey, E. E., Campagno, K. E., McCaughey, S. A., Laties, A. M., Carlsson, L. G., et al. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00242 · Cited by 20 · see citing works
Self-citationAbokyi, S., Shan, S. W., Lam, C. H.-I., Catral, K. P. C., Pan, F., Chan, H. H., To, C. H., & Tse, D. Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22169042 · Cited by 20 · see citing works
Zhang, J., Liu, J., Yue, Y., Wang, L., He, Q., Xu, S., Li, J., Liao, Y., Chen, Y., Wang, S., et al. (2024) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-024-03099-4 · Cited by 19 · see citing works
Self-citationExpression of adenosine receptors in human retinal pigment epithelium cells in vitro.
Wan, W., Cui, D., Yang, X. K., Hu, J., Li, C.-X., Hu, S., Trier, K., & Zeng, J. (2011) · PubMed · Cited by 19 · see citing works
Canfrán‐Duque, A., Barrio, L. C., Lerma, M., de la Peña, G., Serna, J., Pastor, Ó., Lasunción, M. A., & Busto, R. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17030404 · Cited by 18 · see citing works
Light Filtering in a Retinal Pigment Epithelial Cell Culture Model
Zhou, J., & Sparrow, J. R. (2011) · Optometry and Vision Science · doi:10.1097/opx.0b013e3182158cdd · Cited by 18 · see citing works
CD151 Maintains Endolysosomal Protein Quality to Inhibit Vascular Inflammation
Chen, J., Ding, Y., Jiang, C. Y., Qu, R., Wren, J. D., Georgescu, C., Wang, X., Reuter, D. N., Liu, B., Giles, C. B., et al. (2024) · Circulation Research · doi:10.1161/circresaha.123.323190 · Cited by 15 · see citing works
Gao, Y. J., Hu, Y., Liu, Q., Li, X., Li, X., Kim, C., James, T. D., Li, J., Chen, X., & Guo, Y. (2021) · Angewandte Chemie · doi:10.1002/ange.202101278 · Cited by 16 · see citing works
Ageing of the Retina and Retinal Pigment Epithelium
Boulton, M. (2012) · Springer eBooks · doi:10.1007/978-3-642-22107-1_3 · Cited by 15 · see citing works
Lu, W., Campagno, K. E., Tso, H., Cenaj, A., Laties, A. M., Carlsson, L. M. S., & Mitchell, C. H. (2019) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.19-27241 · Cited by 14 · see citing works
Self-citationCellular Assays for Drug Discovery in Genetic Disorders of Intracellular Trafficking
Matteis, M. A. D., Vicinanza, M., Venditti, R., & Wilson, C. (2013) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-091212-153415 · Cited by 13 · see citing works
Age-related dysfunction of the autophago-lysosomal pathway in human endothelial cells
Mai, S., Brehm, N., Auburger, G. W. J., Bereiter‐Hahn, J., & Jendrach, M. (2019) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-019-02288-x · Cited by 13 · see citing works
Genetic susceptibility to hydroxychloroquine retinal toxicity
Mack, H. G., Kowalski, T., Lucattini, A., Symons, R. C. A., Wicks, I., & Hall, A. (2020) · Ophthalmic Genetics · doi:10.1080/13816810.2020.1747093 · Cited by 13 · see citing works
Pan, H.-Y., & Valapala, M. (2021) · Cells · doi:10.3390/cells10102504 · Cited by 10 · see citing works
Modulation of V-ATPase by βA3/A1-Crystallin in Retinal Pigment Epithelial Cells
Valapala, M., Sergeev, Y. V., Wawrousek, E. F., Hose, S., Zigler, J. S., & Sinha, D. (2015) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-17121-0_104 · Cited by 10 · see citing works
- Authors
- Liu, J., Lu, W., Reigada, D., Nguyen, J., Laties, A. M., & Mitchell, C. H.
- Affiliations
- University of Pennsylvania (US)
- From the Departments of Physiology and
- Venue
- Investigative Opthalmology & Visual Science
- Published
- 2008-02-01
- Volume
- 49
- Issue
- 2
- Pages
- 772
- ISSN
- 0146-0404 (ISSN-L)
- 1552-5783
- PMC
- PMC2279299
- OpenAlex
- W1964730685
- Cited by
- 141
- References
- 63
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 9 · 2023: 5 · 2022: 4 · 2021: 10 · 2020: 11 · 2019: 8 · 2018: 11 · 2017: 8 · 2016: 8 · 2015: 9 · 2014: 12 · 2013: 10 · 2012: 9
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Investigative Ophthalmology & Visual Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Eye Institute (EY 017045, EY 015537, EY001583, R01EY013434, R01EY015537, EY-013434, R24EY017045, P30EY001583)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- lysosomal pH, retinal pigment epithelium, ARPE-19 cells, A2E, lysosomal acidification, cyclic AMP, adenosine A2A receptor, beta-adrenergic receptors, Gs protein coupling, lysosomal enzyme activity, macular degeneration
- MeSH terms
- Cyclic AMP, Animals, Cattle, Cells, Cultured, Chloroquine, Humans, Hydrogen-Ion Concentration, Lysosomes, Mice, Inbred C57BL, Pigment Epithelium of Eye, Receptors, Adrenergic, beta, Retinoids, RNA, Messenger, Tamoxifen, Mice, Knockout, ATP-Binding Cassette Transporters, Recovery of Function, Reverse Transcriptase Polymerase Chain Reaction, Photoreceptor Cells, Vertebrate, Receptor, Adenosine A2A, Mice
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