{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T07:18:13Z","timestamp":1783149493760,"version":"3.54.6"},"reference-count":53,"publisher":"Wiley","license":[{"start":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T00:00:00Z","timestamp":1575590400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Region of Nouvelle Aquitaine"},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"name":"association DMLA"},{"name":"Fond Alienor"},{"name":"CHU Poitiers"},{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2019,12,6]]},"abstract":"<jats:p>Age-related macular degeneration (AMD) is characterized by retinal pigment epithelial (RPE) cell dysfunction beginning at early stages of the disease. The lack of an appropriate <jats:italic>in vitro<\/jats:italic> model is a major limitation in understanding the mechanisms leading to the occurrence of AMD. This study compared human-induced pluripotent stem cell- (hiPSC-) RPE cells derived from atrophic AMD patients (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\"><mml:mn>77<\/mml:mn><mml:mtext>\u2009<\/mml:mtext><mml:mtext>y<\/mml:mtext><mml:mo>\/<\/mml:mo><mml:mtext>o<\/mml:mtext><mml:mo>\u00b1<\/mml:mo><mml:mn>7<\/mml:mn><\/mml:math>) to hiPSC-RPE cells derived from healthy elderly individuals with no drusen or pigmentary alteration (<mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\"><mml:mn>62.5<\/mml:mn><mml:mtext>\u2009<\/mml:mtext><mml:mtext>y<\/mml:mtext><mml:mo>\/<\/mml:mo><mml:mtext>o<\/mml:mtext><mml:mo>\u00b1<\/mml:mo><mml:mn>17.5<\/mml:mn><\/mml:math>). Control and AMD hiPSC-RPE cell lines were characterized by immunofluorescence, flow cytometry, and electronic microscopy. The toxicity level of iron after Fe-NTA treatment was evaluated by an MTT test and by the detection of dichloro-dihydro-fluorescein diacetate. Twelve hiPSC-RPE cell lines (6 AMD and 6 controls) were used for the experiment. Under basal conditions, all hiPSC-RPE cells expressed a phenotypic profile of senescent cells with rounded mitochondria at passage 2. However, the treatment with Fe-NTA induced higher reactive oxygen species production and cell death in hiPSC-RPE AMD cells than in hiPSC-RPE Control cells. Interestingly, functional analysis showed differences in lysosomal activity between the two populations. Indeed, Cathepsin B activity was higher in hiPSC-RPE AMD cells compared to hiPSC-RPE Control cells in basal condition and link to a pH more acidic in this cell population. Moreover, oxidative stress exposure leads to an increase of Cathepsin D immature form levels in both populations, but in a higher proportion in hiPSC-RPE AMD cells. These findings could demonstrate that hiPSC-RPE AMD cells have a typical disease phenotype compared to hiPSC-RPE Control cells.<\/jats:p>","DOI":"10.1155\/2019\/5637075","type":"journal-article","created":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T23:34:13Z","timestamp":1575675253000},"page":"1-15","source":"Crossref","is-referenced-by-count":10,"title":["Cathepsin B pH-Dependent Activity Is Involved in Lysosomal Dysregulation in Atrophic Age-Related Macular Degeneration"],"prefix":"10.1155","volume":"2019","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9766-5759","authenticated-orcid":true,"given":"Audrey","family":"Voisin","sequence":"first","affiliation":[{"name":"University of Poitiers, Laboratoire de Neurosciences Exp\u00e9rimentales et Cliniques, Equipe Th\u00e9rapie Cellulaire dans les Pathologies C\u00e9r\u00e9brales, Poitiers F-86073, France"},{"name":"INSERM, U1084, Laboratoire de Neurosciences Exp\u00e9rimentales et Cliniques, Equipe Th\u00e9rapie Cellulaire 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