{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:11:02Z","timestamp":1787505062793,"version":"build-2736575974"},"reference-count":66,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,22]],"date-time":"2021-08-22T00:00:00Z","timestamp":1629590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004377","name":"Hong Kong Polytechnic University","doi-asserted-by":"publisher","award":["PolyU Central Research Grant 1ZE6H, GYBQT"],"award-info":[{"award-number":["PolyU Central Research Grant 1ZE6H, GYBQT"]}],"id":[{"id":"10.13039\/501100004377","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"publisher","award":["Hong Kong PhD Fellowship, UGC\/GEN\/456\/08, UGC\/456\/09"],"award-info":[{"award-number":["Hong Kong PhD Fellowship, UGC\/GEN\/456\/08, UGC\/456\/09"]}],"id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In age-related macular degeneration (AMD), hydroquinone (HQ)-induced oxidative damage in retinal pigment epithelium (RPE) is believed to be an early event contributing to dysregulation of inflammatory cytokines and vascular endothelial growth factor (VEGF) homeostasis. However, the roles of antioxidant mechanisms, such as autophagy and the ubiquitin-proteasome system, in modulating HQ-induced oxidative damage in RPE is not well-understood. This study utilized an in-vitro AMD model involving the incubation of human RPE cells (ARPE-19) with HQ. In comparison to hydrogen peroxide (H2O2), HQ induced fewer reactive oxygen species (ROS) but more oxidative damage as characterized by protein carbonyl levels, mitochondrial dysfunction, and the loss of cell viability. HQ blocked the autophagy flux and increased proteasome activity, whereas H2O2 did the opposite. Moreover, the lysosomal membrane-stabilizing protein LAMP2 and cathepsin D levels declined with HQ exposure, suggesting loss of lysosomal membrane integrity and function. Accordingly, HQ induced lysosomal alkalization, thereby compromising the acidic pH needed for optimal lysosomal degradation. Pretreatment with MG132, a proteasome inhibitor and lysosomal stabilizer, upregulated LAMP2 and autophagy and prevented HQ-induced oxidative damage in wildtype RPE cells but not cells transfected with shRNA against ATG5. This study demonstrated that lysosomal dysfunction underlies autophagy defects and oxidative damage induced by HQ in human RPE cells and supports lysosomal stabilization with the proteasome inhibitor MG132 as a potential remedy for oxidative damage in RPE and AMD.<\/jats:p>","DOI":"10.3390\/ijms22169042","type":"journal-article","created":{"date-parts":[[2021,8,22]],"date-time":"2021-08-22T21:47:52Z","timestamp":1629668872000},"page":"9042","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Targeting Lysosomes to Reverse Hydroquinone-Induced Autophagy Defects and Oxidative Damage in Human Retinal Pigment Epithelial Cells"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8808-1340","authenticated-orcid":false,"given":"Samuel","family":"Abokyi","sequence":"first","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China"},{"name":"Department of Optometry & Vision Science, College of Health and Allied Science, University of Cape Coast, Cape Coast 00233, Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6876-9914","authenticated-orcid":false,"given":"Sze-Wan","family":"Shan","sequence":"additional","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christie Hang-I","family":"Lam","sequence":"additional","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk Patrick","family":"Catral","sequence":"additional","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5256-4380","authenticated-orcid":false,"given":"Feng","family":"Pan","sequence":"additional","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China"},{"name":"Centre for Eye and Vision Research, 17W Hong Kong Science Park, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8516-4711","authenticated-orcid":false,"given":"Henry Ho-Lung","family":"Chan","sequence":"additional","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China"},{"name":"Centre for Eye and Vision Research, 17W Hong Kong Science Park, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1938-8397","authenticated-orcid":false,"given":"Chi-Ho","family":"To","sequence":"additional","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China"},{"name":"Centre for Eye and Vision Research, 17W Hong Kong Science Park, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7561-9121","authenticated-orcid":false,"given":"Dennis Yan-Yin","family":"Tse","sequence":"additional","affiliation":[{"name":"School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China"},{"name":"Centre for Eye and Vision Research, 17W Hong Kong Science Park, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"757","DOI":"10.2147\/CIA.S158513","article-title":"Oxidative stress, aging, and diseases","volume":"13","author":"Liguori","year":"2018","journal-title":"Clin. 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