{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:58:25Z","timestamp":1791928705043,"version":"4.3.4"},"reference-count":36,"publisher":"Association for Research in Vision and Ophthalmology (ARVO)","issue":"8","license":[{"start":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T00:00:00Z","timestamp":1563408000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Invest. Ophthalmol. Vis. Sci."],"published-print":{"date-parts":[[2019,7,18]]},"DOI":"10.1167\/iovs.19-27241","type":"journal-article","created":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T17:30:21Z","timestamp":1563471021000},"page":"3046","source":"Crossref","is-referenced-by-count":12,"title":["Oral Delivery of the P2Y\n                    <sub>12<\/sub>\n                    Receptor Antagonist Ticagrelor Prevents Loss of Photoreceptors in an ABCA4\n                    <sup>\u2212\/\u2212<\/sup>\n                    Mouse Model of Retinal Degeneration"],"prefix":"10.1167","volume":"60","author":[{"given":"Wennan","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith E.","family":"Campagno","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huen-Yee","family":"Tso","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Cenaj","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan M.","family":"Laties","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif G.","family":"Carlsson","sequence":"additional","affiliation":[{"name":"Bioscience Cardiovascular Research and Early Development Cardiovascular, Renal and Metabolism BioPhamaceuticals R&D, AstraZeneca, Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire H.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, University of Pennsylvania, Philadelphia, Pennsylvania, United States"},{"name":"Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States"},{"name":"Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27","reference":[{"key":"i1552-5783-60-8-3046-b01","doi-asserted-by":"crossref","unstructured":"Nixon RA. New perspectives on lysosomes in ageing and neurodegenerative disease. Age Res Rev. 2016; 32: 1.","DOI":"10.1016\/j.arr.2016.11.001"},{"key":"i1552-5783-60-8-3046-b02","doi-asserted-by":"crossref","unstructured":"Sparrow JR, Boulton M. RPE lipofuscin and its role in retinal pathobiology. Exp Eye Res. 2005; 80: 595\u2013606.","DOI":"10.1016\/j.exer.2005.01.007"},{"key":"i1552-5783-60-8-3046-b03","doi-asserted-by":"crossref","unstructured":"Sparrow JR, Dowling JE, Bok D. Understanding RPE lipofuscin. Invest Ophthalmol Vis Sci. 2013; 54: 8325\u20138326.","DOI":"10.1167\/iovs.13-13214"},{"key":"i1552-5783-60-8-3046-b04","doi-asserted-by":"crossref","unstructured":"Holz FG, Steinberg JS, Gobel A, Fleckenstein M, Schmitz-Valckenberg S. Fundus autofluorescence imaging in dry AMD: 2014 Jules Gonin lecture of the Retina Research Foundation. Graefes Arch Clin Exp Ophthalmol. 2015; 253: 7\u201316.","DOI":"10.1007\/s00417-014-2858-1"},{"key":"i1552-5783-60-8-3046-b05","doi-asserted-by":"crossref","unstructured":"Finnemann SC, Leung LW, Rodriguez-Boulan E. The lipofuscin component A2E selectively inhibits phagolysosomal degradation of photoreceptor phospholipid by the retinal pigment epithelium. Proc Natl Acad Sci U S A. 2002; 99: 3842\u20133847.","DOI":"10.1073\/pnas.052025899"},{"key":"i1552-5783-60-8-3046-b06","doi-asserted-by":"crossref","unstructured":"Grey AC, Crouch RK, Koutalos Y, Schey KL, Ablonczy Z. Spatial localization of A2E in the retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2011; 52: 3926\u20133933.","DOI":"10.1167\/iovs.10-7020"},{"key":"i1552-5783-60-8-3046-b07","doi-asserted-by":"crossref","unstructured":"Liu J, Lu W, Reigada D, et al. Restoration of lysosomal pH in RPE cells from cultured human and ABCA4(-\/-) mice: pharmacologic approaches and functional recovery. Invest Ophthalmol Vis Sci. 2008; 49: 772\u2013780.","DOI":"10.1167\/iovs.07-0675"},{"key":"i1552-5783-60-8-3046-b08","doi-asserted-by":"crossref","unstructured":"Guha S, Coffey EE, Lu W, et al. Approaches for detecting lysosomal alkalinization and impaired degradation in fresh and cultured RPE cells: evidence for a role in retinal degenerations. Exp Eye Res. 2014; 126: 68\u201376.","DOI":"10.1016\/j.exer.2014.05.013"},{"key":"i1552-5783-60-8-3046-b09","doi-asserted-by":"crossref","unstructured":"Guha S, Liu J, Baltazar GC, Laties AM, Mitchell CH. Rescue of compromised lysosomes enhances degradation of photoreceptor outer segments and reduce lipofuscin-like autofluorescence Adv Exp Med Biol. 2014; 801: 105\u2013111","DOI":"10.1007\/978-1-4614-3209-8_14"},{"key":"i1552-5783-60-8-3046-b10","doi-asserted-by":"crossref","unstructured":"Guha S, Baltazar GC, Coffey EE, et al. Lysosomal alkalinization, lipid oxidation, impaired autophagy and reduced phagosome clearance triggered by P2X7 receptor activation in retinal pigmented epithelial cells. FASEB J. 2013; 27: 4500\u20134509.","DOI":"10.1096\/fj.13-236166"},{"key":"i1552-5783-60-8-3046-b11","doi-asserted-by":"crossref","unstructured":"Liu J, Lu W, Guha S, et al. Cystic fibrosis transmembrane conductance regulator (CFTR) contributes to reacidification of alkalinized lysosomes in RPE cells Am J Physiol Cell Physiol. 2012; 303: C160\u2013C169.","DOI":"10.1152\/ajpcell.00278.2011"},{"key":"i1552-5783-60-8-3046-b12","doi-asserted-by":"crossref","unstructured":"Coffey EE, Beckel JM, Laties AM, Mitchell CH. Lysosomal alkalization and dysfunction in human fibroblasts with the Alzheimer's disease-linked presenilin 1 A246E mutation can be reversed with cAMP. Neuroscience. 2014; 263: 111\u2013124.","DOI":"10.1016\/j.neuroscience.2014.01.001"},{"key":"i1552-5783-60-8-3046-b13","doi-asserted-by":"crossref","unstructured":"Nylander S, Femia EA, Scavone M, et al. Ticagrelor inhibits human platelet aggregation via adenosine in addition to P2Y12 antagonism. J Thromb Haemost. 2013; 11: 1867\u20131876.","DOI":"10.1111\/jth.12360"},{"key":"i1552-5783-60-8-3046-b14","doi-asserted-by":"crossref","unstructured":"Lu W, G\u00f3mez NM, Lim JC, et al. The P2Y12 receptor antagonist ticagrelor reduces lysosomal pH and autofluorescence in retinal pigmented epithelial cells from the ABCA4-\/- mouse model of retinal degeneration. Front Pharmacol. 2018; 9: 242.","DOI":"10.3389\/fphar.2018.00242"},{"key":"i1552-5783-60-8-3046-b15","doi-asserted-by":"crossref","unstructured":"Song H, Rossi EA, Latchney L, et al. Cone and rod loss in Stargardt disease revealed by adaptive optics scanning light ophthalmoscopy. JAMA Ophthalmol. 2015; 133: 1198\u20131203.","DOI":"10.1001\/jamaophthalmol.2015.2443"},{"key":"i1552-5783-60-8-3046-b16","doi-asserted-by":"crossref","unstructured":"Weng J, Mata NL, Azarian SM, et al. Insights into the function of rim protein in photoreceptors and etiology of Stargardt's disease from the phenotype in abcr knockout mice. Cell. 1999; 98: 13\u201323.","DOI":"10.1016\/S0092-8674(00)80602-9"},{"key":"i1552-5783-60-8-3046-b17","doi-asserted-by":"crossref","unstructured":"Lenis TL, Hu J, Ng SY, et al. Expression of ABCA4 in the retinal pigment epithelium and its implications for Stargardt macular degeneration. Proc Nat Acad Sci. 2018; 115: E11120\u2013E11127.","DOI":"10.1073\/pnas.1802519115"},{"key":"i1552-5783-60-8-3046-b18","doi-asserted-by":"crossref","unstructured":"Wu L, Ueda K, Nagasaki T, Sparrow JR. Light damage in Abca4 and Rpe65rd12 mice. Invest Ophthalmol Vis Sci. 2014; 55: 1910\u20131918.","DOI":"10.1167\/iovs.14-13867"},{"key":"i1552-5783-60-8-3046-b19","doi-asserted-by":"crossref","unstructured":"Sillen H, Cook M, Davis P. Determination of ticagrelor and two metabolites in plasma samples by liquid chromatography and mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2010; 878: 2299\u20132306.","DOI":"10.1016\/j.jchromb.2010.06.018"},{"key":"i1552-5783-60-8-3046-b20","doi-asserted-by":"crossref","unstructured":"Roczniak-Ferguson A, Petit CS, Froehlich F, et al. The transcription factor TFEB links mTORC1 signaling to transcriptional control of lysosome homeostasis. Science Signal. 2012; 5: ra42.","DOI":"10.1126\/scisignal.2002790"},{"key":"i1552-5783-60-8-3046-b21","doi-asserted-by":"crossref","unstructured":"Medina DL, Fraldi A, Bouche V, et al. Transcriptional activation of lysosomal exocytosis promotes cellular clearance. Dev Cell. 2011; 21: 421\u2013430.","DOI":"10.1016\/j.devcel.2011.07.016"},{"key":"i1552-5783-60-8-3046-b22","doi-asserted-by":"crossref","unstructured":"Zoncu R, Bar-Peled L, Efeyan A, et al. mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. Science. 2011; 334: 678\u2013683.","DOI":"10.1126\/science.1207056"},{"key":"i1552-5783-60-8-3046-b23","doi-asserted-by":"crossref","unstructured":"Pe\u00f1a-Llopis S, Vega-Rubin-de-Celis S, Schwartz JC, et al. Regulation of TFEB and V-ATPases by mTORC1. EMBO J. 2011; 30: 3242\u20133258.","DOI":"10.1038\/emboj.2011.257"},{"key":"i1552-5783-60-8-3046-b24","doi-asserted-by":"crossref","unstructured":"Brandstetter C, Mohr LKM, Latz E, Holz FG, Krohne TU. Light induces NLRP3 inflammasome activation in retinal pigment epithelial cells via lipofuscin-mediated photooxidative damage. J Mol Med (Berl). 2015; 93: 905\u2013916.","DOI":"10.1007\/s00109-015-1275-1"},{"key":"i1552-5783-60-8-3046-b25","doi-asserted-by":"crossref","unstructured":"Wang L, Schmidt S, Larsen PP, et al. Efficacy of novel selective NLRP3 inhibitors in human and murine retinal pigment epithelial cells. J Mol Med (Berl). 2019; 97: 523\u2013532.","DOI":"10.1007\/s00109-019-01753-5"},{"key":"i1552-5783-60-8-3046-b26","doi-asserted-by":"crossref","unstructured":"Tseng WA, Thein T, Kinnunen K, et al. NLRP3 inflammasome activation in retinal pigment epithelial cells by lysosomal destabilization: implications for age-related macular degeneration. Invest Ophthalmol Vis Sci. 2013; 54: 110\u2013120.","DOI":"10.1167\/iovs.12-10655"},{"key":"i1552-5783-60-8-3046-b27","doi-asserted-by":"crossref","unstructured":"Samie M, Wang X, Zhang X, et al. A TRP channel in the lysosome regulates large particle phagocytosis via focal exocytosis. Dev Cell. 2013; 26: 511\u2013524.","DOI":"10.1016\/j.devcel.2013.08.003"},{"key":"i1552-5783-60-8-3046-b28","doi-asserted-by":"crossref","unstructured":"M\u00e1s GN, Lu W, Lim JC, et al. Robust lysosomal calcium signaling through channel TRPML1 is impaired by lipofuscin accumulation FASEB J. 2018; 32: 782\u2013794.","DOI":"10.1096\/fj.201700220RR"},{"key":"i1552-5783-60-8-3046-b29","doi-asserted-by":"crossref","unstructured":"Charbel Issa P, Barnard AR, Singh MS, et al. Fundus autofluorescence in the Abca4-\/- mouse model of Stargardt disease--correlation with accumulation of A2E, retinal function, and histology. Invest Ophthalmol Vis Sci. 2013; 54: 5602\u20135612.","DOI":"10.1167\/iovs.13-11688"},{"key":"i1552-5783-60-8-3046-b30","doi-asserted-by":"crossref","unstructured":"Platania CBM, Giurdanella G, Di Paola L, et al. P2X7 receptor antagonism: Implications in diabetic retinopathy. Biochem Pharmacol. 2017; 138: 130\u2013139.","DOI":"10.1016\/j.bcp.2017.05.001"},{"key":"i1552-5783-60-8-3046-b31","doi-asserted-by":"crossref","unstructured":"Kupenova P, Popova E, Vitanova L. Purinergic modulation of frog electroretinographic responses: The role of the ionotropic receptor P2X7. Vis Neurosci. 2017; 34: E015.","DOI":"10.1017\/S0952523817000128"},{"key":"i1552-5783-60-8-3046-b32","unstructured":"Ventura ALM, dos Santos-Rodrigues A, Mitchell CH, Faillace MP. Purinergic signaling in the retina: From development to disease. Br Res Bull. In press."},{"key":"i1552-5783-60-8-3046-b33","doi-asserted-by":"crossref","unstructured":"Sanderson J, Dartt DA, Trinkaus-Randall V, et al. Purines in the eye: recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Muller cells, lens, trabecular meshwork, cornea and lacrimal gland. Exp Eye Res. 2014; 127: 270\u2013279.","DOI":"10.1016\/j.exer.2014.08.009"},{"key":"i1552-5783-60-8-3046-b34","doi-asserted-by":"crossref","unstructured":"Held P, Himmelmann A, Ditmarsch M. Ticagrelor for the treatment of atherosclerotic disease: insights from the PARTHENON clinical development program. Future Cardiol. 2016; 12: 405\u2013418.","DOI":"10.2217\/fca-2016-0028"},{"key":"i1552-5783-60-8-3046-b35","doi-asserted-by":"crossref","unstructured":"Storey RF, Angiolillo DJ, Patil SB, et al. Inhibitory effects of ticagrelor compared with clopidogrel on platelet function in patients with acute coronary syndromes: the PLATO (PLATelet inhibition and patient Outcomes) PLATELET substudy. J Am Coll Cardiol. 2010; 56: 1456\u20131462.","DOI":"10.1016\/j.jacc.2010.03.100"},{"key":"i1552-5783-60-8-3046-b36","doi-asserted-by":"crossref","unstructured":"Storey RF, Angiolillo DJ, Bonaca MP, et al. Platelet inhibition with ticagrelor 60 mg versus 90 mg twice daily in the PEGASUS-TIMI 54 trial. J Am Coll Cardiol. 2016; 67: 1145\u20131154.","DOI":"10.1016\/j.jacc.2015.12.062"}],"container-title":["Investigative Opthalmology &amp; Visual Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2738411","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:31:07Z","timestamp":1791927067000},"score":1,"resource":{"primary":{"URL":"https:\/\/iovs.arvojournals.org\/article.aspx?articleid=2738411"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,18]]},"references-count":36,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2019,7,1]]}},"URL":"https:\/\/doi.org\/10.1167\/iovs.19-27241","relation":{},"ISSN":["1552-5783"],"issn-type":[{"value":"1552-5783","type":"print"}],"subject":[],"published":{"date-parts":[[2019,7,18]]}}}