{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T05:43:34Z","timestamp":1771307014358,"version":"3.50.1"},"reference-count":77,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T00:00:00Z","timestamp":1613520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010757","name":"National Centre for the Replacement Refinement and Reduction of Animals in Research","doi-asserted-by":"publisher","award":["NC\/L001152\/1"],"award-info":[{"award-number":["NC\/L001152\/1"]}],"id":[{"id":"10.13039\/501100010757","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011718","name":"Macular Society","doi-asserted-by":"publisher","award":["PhD Studentship"],"award-info":[{"award-number":["PhD Studentship"]}],"id":[{"id":"10.13039\/100011718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000310","name":"Retina UK","doi-asserted-by":"publisher","award":["GR590"],"award-info":[{"award-number":["GR590"]}],"id":[{"id":"10.13039\/501100000310","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000615","name":"Fight for Sight UK","doi-asserted-by":"publisher","award":["1485\/86"],"award-info":[{"award-number":["1485\/86"]}],"id":[{"id":"10.13039\/501100000615","id-type":"DOI","asserted-by":"publisher"}]},{"name":"ARUK South Coast Network","award":["Pump-prime award"],"award-info":[{"award-number":["Pump-prime award"]}]},{"name":"Gift of Sight Appeal","award":["Postdoctoral award"],"award-info":[{"award-number":["Postdoctoral award"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Alzheimer\u2019s disease-associated amyloid beta (A\u03b2) proteins accumulate in the outer retina with increasing age and in eyes of age-related macular degeneration (AMD) patients. To study A\u03b2-induced retinopathy, wild-type mice were injected with nanomolar human oligomeric A\u03b21-42, which recapitulate the A\u03b2 burden reported in human donor eyes. In vitro studies investigated the cellular effects of A\u03b2 in endothelial and retinal pigment epithelial (RPE) cells. Results show subretinal A\u03b2-induced focal AMD-like pathology within 2 weeks. A\u03b2 exposure caused endothelial cell migration, and morphological and barrier alterations to the RPE. A\u03b2 co-localized to late-endocytic compartments of RPE cells, which persisted despite attempts to clear it through upregulation of lysosomal cathepsin B, revealing a novel mechanism of lysosomal impairment in retinal degeneration. The rapid upregulation of cathepsin B was out of step with the prolonged accumulation of A\u03b2 within lysosomes, and contrasted with enzymatic responses to internalized photoreceptor outer segments (POS). Furthermore, RPE cells exposed to A\u03b2 were identified as deficient in cargo-carrying lysosomes at time points that are critical to POS degradation. These findings imply that A\u03b2 accumulation within late-endocytic compartments, as well as lysosomal deficiency, impairs RPE function over time, contributing to visual defects seen in aging and AMD eyes.<\/jats:p>","DOI":"10.3390\/cells10020413","type":"journal-article","created":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T01:47:33Z","timestamp":1613526453000},"page":"413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Oligomeric A\u03b21-42 Induces an AMD-Like Phenotype and Accumulates in Lysosomes to Impair RPE Function"],"prefix":"10.3390","volume":"10","author":[{"given":"Savannah A.","family":"Lynn","sequence":"first","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP 806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Unit, University of Southampton, MP12, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny A.","family":"Scott","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP 806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosie","family":"Munday","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP 806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roshni S.","family":"Desai","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP 806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0399-359X","authenticated-orcid":false,"given":"Eloise","family":"Keeling","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP 806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1862-1900","authenticated-orcid":false,"given":"Ruaridh","family":"Weaterton","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP 806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3439-2236","authenticated-orcid":false,"given":"Alexander","family":"Simpson","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP 806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dillon","family":"Davis","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP 806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Freeman","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP 806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1856-3982","authenticated-orcid":false,"given":"David S.","family":"Chatelet","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Unit, University of Southampton, MP12, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Page","sequence":"additional","affiliation":[{"name":"Biomedical Imaging Unit, University of Southampton, MP12, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela J.","family":"Cree","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP 806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2573-9536","authenticated-orcid":false,"given":"Helena","family":"Lee","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP 806, Tremona Road, Southampton SO16 6YD, UK"},{"name":"Eye Unit, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3727-9258","authenticated-orcid":false,"given":"Tracey A.","family":"Newman","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP 806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5541-4305","authenticated-orcid":false,"given":"Andrew J.","family":"Lotery","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP 806, Tremona Road, Southampton SO16 6YD, UK"},{"name":"Eye Unit, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1027-6938","authenticated-orcid":false,"given":"J. Arjuna","family":"Ratnayaka","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, MP 806, Tremona Road, Southampton SO16 6YD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.preteyeres.2015.09.002","article-title":"Defects in retinal pigment epithelial cell proteolysis and the pathology associated with age-related macular degeneration","volume":"51","author":"Ferrington","year":"2016","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.preteyeres.2011.12.001","article-title":"The bisretinoids of retinal pigment epithelium","volume":"31","author":"Sparrow","year":"2012","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.ophtha.2016.12.002","article-title":"Imaging Protocols in Clinical Studies in Advanced Age-Related Macular Degeneration: Recommendations from Classification of Atrophy Consensus Meetings","volume":"124","author":"Holz","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.ajo.2006.11.041","article-title":"Progression of geographic atrophy and impact of fundus autofluorescence patterns in age-related macular degeneration","volume":"143","author":"Holz","year":"2007","journal-title":"Am. J. Ophthalmol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1167\/iovs.07-1466","article-title":"Prevalence and morphology of druse types in the macula and periphery of eyes with age-related maculopathy","volume":"49","author":"Rudolf","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"538","DOI":"10.4103\/1673-5374.205083","article-title":"The complexities underlying age-related macular degeneration: Could amyloid beta play an important role?","volume":"12","author":"Lynn","year":"2017","journal-title":"Neural Regen. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/eye.2015.100","article-title":"Dementia of the eye: The role of amyloid beta in retinal degeneration","volume":"29","author":"Ratnayaka","year":"2015","journal-title":"Eye"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.preteyeres.2011.02.004","article-title":"Parallel findings in age-related macular degeneration and Alzheimer\u2019s disease","volume":"30","year":"2011","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"11830","DOI":"10.1073\/pnas.192203399","article-title":"The Alzheimer\u2019s A beta -peptide is deposited at sites of complement activation in pathologic deposits associated with aging and age-related macular degeneration","volume":"99","author":"Johnson","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.exer.2003.10.011","article-title":"Characterization of beta amyloid assemblies in drusen: The deposits associated with aging and age-related macular degeneration","volume":"78","author":"Anderson","year":"2004","journal-title":"Exp. Eye Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1073\/pnas.1413347112","article-title":"Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye","volume":"112","author":"Thompson","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1167\/iovs.09-4207","article-title":"Soluble and mature amyloid fibrils in drusen deposits","volume":"51","author":"Isas","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1172\/JCI25843","article-title":"Drusen deposits associated with aging and age-related macular degeneration contain nonfibrillar amyloid oligomers","volume":"116","author":"Luibl","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_14","first-page":"184","article-title":"Amyloid-beta is found in drusen from some age-related macular degeneration retinas, but not in drusen from normal retinas","volume":"9","author":"Dentchev","year":"2003","journal-title":"Mol. Vis."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Hoh, K.J., Lenassi, E., and Jeffery, G. (2010). Viewing ageing eyes: Diverse sites of amyloid Beta accumulation in the ageing mouse retina and the up-regulation of macrophages. PLoS ONE.","DOI":"10.1371\/journal.pone.0013127"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11900","DOI":"10.1073\/pnas.0503015102","article-title":"Apolipoprotein E allele-dependent pathogenesis: A model for age-related retinal degeneration","volume":"102","author":"Malek","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1016\/j.neurobiolaging.2014.03.008","article-title":"Intracellular amyloid beta alters the tight junction of retinal pigment epithelium in 5XFAD mice","volume":"35","author":"Park","year":"2014","journal-title":"Neurobiol. Aging"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Catchpole, I., Germaschewski, V., Hoh, K.J., von Leithner, P.L., Ford, S., Gough, G., Adamson, P., Overend, P., Hilpert, J., and Lopez, F.J. (2013). Systemic Administration of Abeta mAb Reduces Retinal Deposition of Abeta and Activated Complement C3 in Age-Related Macular Degeneration Mouse Model. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0065518"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E279","DOI":"10.1073\/pnas.1100901108","article-title":"Anti-amyloid therapy protects against retinal pigmented epithelium damage and vision loss in a model of age-related macular degeneration","volume":"108","author":"Ding","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Shi, H., Koronyo, Y., Rentsendorj, A., Regis, G.C., Sheyn, J., Fuchs, D.T., Kramerov, A.A., Ljubimov, A.V., Dumitrascu, O.M., and Rodriguez, A.R. (2020). Identification of early pericyte loss and vascular amyloidosis in Alzheimer\u2019s disease retina. Acta Neuropathol.","DOI":"10.1007\/s00401-020-02134-w"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7227","DOI":"10.1073\/pnas.0501536102","article-title":"A common haplotype in the complement regulatory gene factor H (HF1\/CFH) predisposes individuals to age-related macular degeneration","volume":"102","author":"Hageman","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1093\/protein\/gzr020","article-title":"A standardized and biocompatible preparation of aggregate-free amyloid beta peptide for biophysical and biological studies of Alzheimer\u2019s disease","volume":"24","author":"Broersen","year":"2011","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1042\/BJ20110749","article-title":"Visualization of co-localization in Abeta42-administered neuroblastoma cells reveals lysosome damage and autophagosome accumulation related to cell death","volume":"441","author":"Soura","year":"2012","journal-title":"Biochem. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.yapd.2015.04.012","article-title":"Gene Therapy for Blinding Pediatric Eye Disorders","volume":"62","author":"Dumitrescu","year":"2015","journal-title":"Adv. Pediatr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.tice.2017.06.003","article-title":"Ex-vivo models of the Retinal Pigment Epithelium (RPE) in long-term culture faithfully recapitulate key structural and physiological features of native RPE","volume":"49","author":"Lynn","year":"2017","journal-title":"Tissue Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.12688\/f1000research.15409.1","article-title":"A convenient protocol for establishing a human cell culture model of the outer retina","volume":"7","author":"Lynn","year":"2018","journal-title":"F1000Research"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"440","DOI":"10.4161\/cam.36224","article-title":"An introduction to the wound healing assay using live-cell microscopy","volume":"8","author":"Jonkman","year":"2014","journal-title":"Cell Adhes. Migr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6282","DOI":"10.1167\/iovs.12-9721","article-title":"Using flow cytometry to compare the dynamics of photoreceptor outer segment phagocytosis in iPS-derived RPE cells","volume":"53","author":"Westenskow","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1800951","DOI":"10.1002\/mnfr.201800951","article-title":"Oxidative Stress and Dysfunctional Intracellular Traffic Linked to an Unhealthy Diet Results in Impaired Cargo Transport in the Retinal Pigment Epithelium (RPE)","volume":"63","author":"Keeling","year":"2019","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3993","DOI":"10.1529\/biophysj.103.038422","article-title":"Automatic and quantitative measurement of protein-protein colocalization in live cells","volume":"86","author":"Costes","year":"2004","journal-title":"Biophys. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1167\/iovs.09-3755","article-title":"Apical-to-basolateral transcytosis of photoreceptor outer segments induced by lipid peroxidation products in human retinal pigment epithelial cells","volume":"51","author":"Krohne","year":"2010","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1006\/exer.1997.0339","article-title":"Porcine iris pigment epithelial cells can take up retinal outer segments","volume":"65","author":"Schraermeyer","year":"1997","journal-title":"Exp. Eye Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/978-1-62703-080-9_20","article-title":"Analysis of photoreceptor outer segment phagocytosis by RPE cells in culture","volume":"935","author":"Mao","year":"2013","journal-title":"Methods Mol. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"LaVail, M.M., Hollyfield, J.G., and Anderson, R.E. (2003). Role of avb5 integrin in regulating phagocytosis by the retinal pigment epithelium. Retinal Degenerations, Springer. Advances in Experimental Medicine and Biology.","DOI":"10.1007\/978-1-4615-0067-4"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1084\/jem.194.9.1289","article-title":"Differential Roles of CD36 and \u03b1v\u03b25 Integrin in Photoreceptor Phagocytosis by the Retinal Pigment Epithelium","volume":"194","author":"Finnemann","year":"2001","journal-title":"J. Exp. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.exer.2014.01.010","article-title":"Understanding photoreceptor outer segment phagocytosis: Use and utility of RPE cells in culture","volume":"126","author":"Mazzoni","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.3233\/JAD-2010-100210","article-title":"Differential accumulation of secreted AbetaPP metabolites in ocular fluids","volume":"20","author":"Prakasam","year":"2010","journal-title":"J. Alzheimers Dis"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2793","DOI":"10.1172\/JCI24635","article-title":"The potential role of amyloid beta in the pathogenesis of age-related macular degeneration","volume":"115","author":"Yoshida","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.exer.2015.06.027","article-title":"Reduction of amyloid-beta levels in mouse eye tissues by intra-vitreally delivered neprilysin","volume":"138","author":"Parthasarathy","year":"2015","journal-title":"Exp. Eye Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Keeling, E., Lotery, A.J., Tumbarello, D.A., and Ratnayaka, J.A. (2018). Impaired Cargo Clearance in the Retinal Pigment Epithelium (RPE) Underlies Irreversible Blinding Diseases. Cells, 7.","DOI":"10.20944\/preprints201801.0269.v1"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","article-title":"Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)","volume":"12","author":"Klionsky","year":"2016","journal-title":"Autophagy"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5461","DOI":"10.3390\/ijms12095461","article-title":"Selection of candidate housekeeping genes for normalization in human postmortem brain samples","volume":"12","author":"Penna","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1007\/s00417-015-2970-x","article-title":"Plasma levels of amyloid beta and other proinflammatory mediators in patients with age-related macular degeneration","volume":"253","author":"Guymer","year":"2015","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1097\/WNR.0b013e3283497334","article-title":"Retinal amyloid peptides and complement factor H in transgenic models of Alzheimer\u2019s disease","volume":"22","author":"Alexandrov","year":"2011","journal-title":"Neuroreport"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.neurobiolaging.2018.03.017","article-title":"The retina as a window to early dysfunctions of Alzheimer\u2019s disease following studies with a 5xFAD mouse model","volume":"67","author":"Criscuolo","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"40006","DOI":"10.18632\/oncotarget.16967","article-title":"Dry age-related macular degeneration like pathology in aged 5XFAD mice: Ultrastructure and microarray analysis","volume":"8","author":"Park","year":"2017","journal-title":"Oncotarget"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.ophtha.2013.11.023","article-title":"Geographic atrophy: Clinical features and potential therapeutic approaches","volume":"121","author":"Holz","year":"2014","journal-title":"Ophthalmology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s10633-010-9226-1","article-title":"The electroretinogram: A useful tool for evaluating age-related macular disease?","volume":"121","author":"Berrow","year":"2010","journal-title":"Doc. Ophthalmol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3892\/ijmm.2014.1993","article-title":"Subretinal injection of amyloid-beta peptide accelerates RPE cell senescence and retinal degeneration","volume":"35","author":"Liu","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1113\/jphysiol.2005.103754","article-title":"Effects of secreted oligomers of amyloid beta-protein on hippocampal synaptic plasticity: A potent role for trimers","volume":"572","author":"Townsend","year":"2006","journal-title":"J. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Ramanathan, A., Nelson, A., Sagare, A., and Zlokovic, B. (2015). Impaired vascular-mediated clearance of brain amyloid beta in Alzheimer\u2019s disease: The role, regulation and restoration of LRP1. Front. Aging Neurosci., 7.","DOI":"10.3389\/fnagi.2015.00136"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7475","DOI":"10.1038\/s41598-019-43906-z","article-title":"A lasered mouse model of retinal degeneration displays progressive outer retinal pathology providing insights into early geographic atrophy","volume":"9","author":"Ibbett","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"863","DOI":"10.4103\/1673-5374.268972","article-title":"Challenges in studying geographic atrophy (GA) age-related macular degeneration: The potential of a new mouse model with GA-like features","volume":"15","author":"Ratnayaka","year":"2020","journal-title":"Neural Regen. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1111\/j.1474-9726.2009.00456.x","article-title":"Amyloid-beta(1-42) alters structure and function of retinal pigmented epithelial cells","volume":"8","author":"Bruban","year":"2009","journal-title":"Aging Cell"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Bhutto, I.A., Ogura, S., Baldeosingh, R., McLeod, D.S., Lutty, G.A., and Edwards, M.M. (2018). An Acute Injury Model for the Phenotypic Characteristics of Geographic Atrophy. Investig. Ophthalmol. Vis. Sci., 59.","DOI":"10.1167\/iovs.18-24245"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"24317","DOI":"10.1073\/pnas.1912959116","article-title":"Elovanoids counteract oligomeric beta-amyloid-induced gene expression and protect photoreceptors","volume":"116","author":"Do","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1167\/iovs.12-10821","article-title":"Amyloid-beta increases capillary bed density in the adult zebrafish retina","volume":"54","author":"Cunvong","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3738","DOI":"10.1167\/iovs.13-11612","article-title":"Abeta-induced senescent retinal pigment epithelial cells create a proinflammatory microenvironment in AMD","volume":"54","author":"Cao","year":"2013","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"35263","DOI":"10.18632\/oncotarget.5894","article-title":"RAGE mediated intracellular Abeta uptake contributes to the breakdown of tight junction in retinal pigment epithelium","volume":"6","author":"Park","year":"2015","journal-title":"Oncotarget"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1007\/s00018-019-03420-x","article-title":"Senescence in the pathogenesis of age-related macular degeneration","volume":"77","author":"Blasiak","year":"2020","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.bbrc.2012.05.085","article-title":"Elevated amyloid beta production in senescent retinal pigment epithelium, a possible mechanism of subretinal deposition of amyloid beta in age-related macular degeneration","volume":"423","author":"Wang","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Tarau, I.S., Berlin, A., Curcio, C.A., and Ach, T. (2019). The Cytoskeleton of the Retinal Pigment Epithelium: From Normal Aging to Age-Related Macular Degeneration. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143578"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.bbadis.2008.06.003","article-title":"Oligomer-specific Abeta toxicity in cell models is mediated by selective uptake","volume":"1782","author":"Chafekar","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_64","first-page":"2520","article-title":"ESCRTs regulate amyloid precursor protein sorting in multivesicular bodies and intracellular amyloid-beta accumulation","volume":"128","author":"Edgar","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"20324","DOI":"10.1073\/pnas.0911281106","article-title":"Amyloid seeds formed by cellular uptake, concentration, and aggregation of the amyloid-beta peptide","volume":"106","author":"Hu","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"19986","DOI":"10.1074\/jbc.M109.036798","article-title":"Membrane localization of beta-amyloid 1-42 in lysosomes: A possible mechanism for lysosome labilization","volume":"285","author":"Liu","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1146\/annurev-physiol-021014-071649","article-title":"Lysosomal physiology","volume":"77","author":"Xu","year":"2015","journal-title":"Annu. Rev. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Bandyopadhyay, D., Cyphersmith, A., Zapata, J.A., Kim, Y.J., and Payne, C.K. (2014). Lysosome transport as a function of lysosome diameter. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086847"},{"key":"ref_69","unstructured":"Rawlings, N.D., and Salvesen, G. (2013). Handbook of Proteolytic Enzymes, Academic Press."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1159\/000492886","article-title":"Oxidative Stress is the Principal Contributor to Inflammasome Activation in Retinal Pigment Epithelium Cells with Defunct Proteasomes and Autophagy","volume":"49","author":"Piippo","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3034","DOI":"10.1167\/iovs.18-26360","article-title":"Retinal Pigment Epithelium Cell Death Is Associated With NLRP3 Inflammasome Activation by All-trans Retinal","volume":"60","author":"Liao","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Marshall, K.E., Vadukul, D.M., Staras, K., and Serpell, L.C. (2020). Misfolded amyloid-beta-42 impairs the endosomal-lysosomal pathway. Cell. Mol. Life Sci.","DOI":"10.1007\/s00018-020-03464-4"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1177\/41.2.8419462","article-title":"Phagocytosis of outer segments by retinal pigment epithelium: Phagosome-lysosome interaction","volume":"41","author":"Bosch","year":"1993","journal-title":"J. Histochem. Cytochem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/BF02409013","article-title":"Microfluorometric kinetic analysis of cathepsin B activity in single human thyroid follicular epithelial cells using image analysis and continuous monitoring","volume":"28","author":"Kayser","year":"1996","journal-title":"Histochem. J."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.jpba.2014.02.009","article-title":"Evaluation of cathepsin B activity for degrading collagen IV using a surface plasmon resonance method and circular dichroism spectroscopy","volume":"95","author":"Shoji","year":"2014","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.exer.2006.03.009","article-title":"Regulation of cysteine cathepsin expression by oxidative stress in the retinal pigment epithelium\/choroid of the mouse","volume":"83","author":"Alizadeh","year":"2006","journal-title":"Exp. Eye Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"23724","DOI":"10.1073\/pnas.1906643116","article-title":"Genetic LAMP2 deficiency accelerates the age-associated formation of basal laminar deposits in the retina","volume":"116","author":"Notomi","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/2\/413\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:25:00Z","timestamp":1760160300000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/2\/413"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,17]]},"references-count":77,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["cells10020413"],"URL":"https:\/\/doi.org\/10.3390\/cells10020413","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,17]]}}}