{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:28:53Z","timestamp":1791246533041,"version":"4.1.0"},"reference-count":76,"publisher":"National Academy of Sciences","issue":"47","license":[{"start":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T00:00:00Z","timestamp":1573084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["1R01EY025362-01"],"award-info":[{"award-number":["1R01EY025362-01"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["5R21EY023079-02"],"award-info":[{"award-number":["5R21EY023079-02"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,11,19]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Extracellular tissue debris accumulates with aging and in the most prevalent central-vision-threatening eye disorder, age-related macular degeneration (AMD). In this work, we discovered that lysosome-associated membrane protein-2 (LAMP2), a glycoprotein that plays a critical role in lysosomal biogenesis and maturation of autophagosomes\/phagosomes, is preferentially expressed in the outermost, neuroepithelial layer of the retina, the retinal pigment epithelium (RPE), and contributes to the prevention of ultrastructural changes in extracellular basolaminar deposits including lipids and apolipoproteins. LAMP2 thus appears to play an important role in RPE biology, and its apparent decrease with aging and in AMD specimens suggests that its deficiency may accelerate the basolaminar deposit formation and RPE dysfunction seen in these conditions.<\/jats:p>","DOI":"10.1073\/pnas.1906643116","type":"journal-article","created":{"date-parts":[[2019,11,7]],"date-time":"2019-11-07T19:34:12Z","timestamp":1573155252000},"page":"23724-23734","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":92,"title":["Genetic LAMP2 deficiency accelerates the age-associated formation of basal laminar deposits in the retina"],"prefix":"10.1073","volume":"116","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7935-4244","authenticated-orcid":false,"given":"Shoji","family":"Notomi","sequence":"first","affiliation":[{"name":"Angiogenesis Laboratory, Ophthalmology Department, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114;"},{"name":"Department of Ophthalmology, Kyushu University, Fukuoka 812-8582, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Ishihara","sequence":"additional","affiliation":[{"name":"Angiogenesis Laboratory, Ophthalmology Department, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6635-0391","authenticated-orcid":false,"given":"Nikolaos E.","family":"Efstathiou","sequence":"additional","affiliation":[{"name":"Angiogenesis Laboratory, Ophthalmology Department, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Jer","family":"Lee","sequence":"additional","affiliation":[{"name":"Angiogenesis Laboratory, Ophthalmology Department, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114;"},{"name":"Department of Ophthalmology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshio","family":"Hisatomi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kyushu University, Fukuoka 812-8582, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5004-6312","authenticated-orcid":false,"given":"Takashi","family":"Tachibana","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kyushu University, Fukuoka 812-8582, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni K.","family":"Konstantinou","sequence":"additional","affiliation":[{"name":"Angiogenesis Laboratory, Ophthalmology Department, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ueta","sequence":"additional","affiliation":[{"name":"Angiogenesis Laboratory, Ophthalmology Department, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kyushu University, Fukuoka 812-8582, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3447-4074","authenticated-orcid":false,"given":"Daniel E.","family":"Maidana","sequence":"additional","affiliation":[{"name":"Angiogenesis Laboratory, Ophthalmology Department, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kyushu University, Fukuoka 812-8582, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kume","sequence":"additional","affiliation":[{"name":"Department of Medicine, Shiga University of Medical Science, Shiga 520-2192, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroto","family":"Terasaki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kagoshima University, Kagoshima 890-8520, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shozo","family":"Sonoda","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kagoshima University, Kagoshima 890-8520, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Blanz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Young","sequence":"additional","affiliation":[{"name":"Angiogenesis Laboratory, Ophthalmology Department, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiji","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kagoshima University, Kagoshima 890-8520, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koh-Hei","family":"Sonoda","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kyushu University, Fukuoka 812-8582, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Saftig","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry, Kiel University, Kiel D-24098, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kyushu University, Fukuoka 812-8582, Japan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2046-3996","authenticated-orcid":false,"given":"Joan W.","family":"Miller","sequence":"additional","affiliation":[{"name":"Angiogenesis Laboratory, Ophthalmology Department, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Kroemer","sequence":"additional","affiliation":[{"name":"Metabolism, Cancer &amp; Immunity Laboratory, INSERM U1138, Centre de Recherche des Cordeliers, Sorbonne Universit\u00e9, Universit\u00e9 de Paris, Paris 75006, France;"},{"name":"Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif 94800, France;"},{"name":"P\u00f4le de Biologie, H\u00f4pital Europ\u00e9en Georges Pompidou, AP-HP, Paris 75015, France;"},{"name":"Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou 100050, China;"},{"name":"Department of Women\u2019s and Children\u2019s Health, Karolinska Institute, Karolinska University Hospital, Stockholm 171 76, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8622-6478","authenticated-orcid":false,"given":"Demetrios G.","family":"Vavvas","sequence":"additional","affiliation":[{"name":"Angiogenesis Laboratory, Ophthalmology Department, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2019,11,7]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0801537"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2012.07.038"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.06.018"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3459"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2012.10.036"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18-24882"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/eye.1988.106"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/eye.1995.192"},{"key":"e_1_3_3_9_2","first-page":"2435","article-title":"Spectral profiling of autofluorescence associated with lipofuscin, Bruch\u2019s membrane, and sub-RPE deposits in normal and AMD eyes","volume":"43","author":"Marmorstein A. D.","year":"2002","unstructured":"A. D. Marmorstein, L. Y. Marmorstein, H. Sakaguchi, J. G. Hollyfield, Spectral profiling of autofluorescence associated with lipofuscin, Bruch\u2019s membrane, and sub-RPE deposits in normal and AMD eyes. Invest. Ophthalmol. Vis. Sci. 43, 2435\u20132441 (2002).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0000000000001325"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-1466"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2012-301547"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.19-26566"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-21060"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-3755"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.06.012"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004160"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.36184"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.27292"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-13336"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2015.1041699"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2007.00946.x"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.18.12692"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/35022595"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e02-02-0114"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601511"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04-02-0103"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5724"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/35022604"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2008.04.010"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1097\/IAE.0000000000000736"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2006.02.030"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.125.2.231"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-011-1857-8"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.20.7577"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2007.00351.x"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022818"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2009.06.001"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.117.3.329"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/eye.1994.57"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.06-0443"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2017.08.033"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2004.09.017"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201410112"},{"key":"e_1_3_3_45_2","first-page":"443","article-title":"The relationships of age changes in retinal pigment epithelium and Bruch\u2019s membrane","volume":"40","author":"Okubo A.","year":"1999","unstructured":"A. Okubo ., The relationships of age changes in retinal pigment epithelium and Bruch\u2019s membrane. Invest. Ophthalmol. Vis. Sci. 40, 443\u2013449 (1999).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(98)00012-3"},{"key":"e_1_3_3_47_2","first-page":"1236","article-title":"Photoreceptor loss in age-related macular degeneration","volume":"37","author":"Curcio C. A.","year":"1996","unstructured":"C. A. Curcio, N. E. Medeiros, C. L. Millican, Photoreceptor loss in age-related macular degeneration. Invest. Ophthalmol. Vis. Sci. 37, 1236\u20131249 (1996).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-16431"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2011.05.021"},{"key":"e_1_3_3_50_2","first-page":"265","article-title":"Accumulation of cholesterol with age in human Bruch\u2019s membrane","volume":"42","author":"Curcio C. A.","year":"2001","unstructured":"C. A. Curcio, C. L. Millican, T. Bailey, H. S. Kruth, Accumulation of cholesterol with age in human Bruch\u2019s membrane. Invest. Ophthalmol. Vis. Sci. 42, 265\u2013274 (2001).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2005.04.012"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/3813"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.10-5766"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000141858.80738.AA"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1136\/bjophthalmol-2011-300344"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.202491599"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm198"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1006\/exer.1999.0798"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1006\/exer.2001.1094"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.05-0719"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm199"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019456"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2017.10.018"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2014.04.010"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8920-5"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1113421108"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-17121-0_104"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2014.11.002"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2013.153"},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002102200"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.1.3.2017"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.001073"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.23002"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-014-0182-y"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1186\/2047-9158-3-20"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.21635"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1906643116","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1906643116","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T05:04:55Z","timestamp":1649826295000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1906643116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,7]]},"references-count":76,"journal-issue":{"issue":"47","published-print":{"date-parts":[[2019,11,19]]}},"alternative-id":["10.1073\/pnas.1906643116"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1906643116","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,7]]},"assertion":[{"value":"2019-11-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}