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Article

Targeting Lysosomes to Reverse Hydroquinone-Induced Autophagy Defects and Oxidative Damage in Human Retinal Pigment Epithelial Cells

1
School of Optometry, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China
2
Department of Optometry & Vision Science, College of Health and Allied Science, University of Cape Coast, Cape Coast 00233, Ghana
3
Centre for Eye and Vision Research, 17W Hong Kong Science Park, Hong Kong, China
*
Author to whom correspondence should be addressed.
Academic Editors: Janusz Blasiak and Kai Kaarniranta
Int. J. Mol. Sci. 2021, 22(16), 9042; https://doi.org/10.3390/ijms22169042
Received: 16 July 2021 / Revised: 19 August 2021 / Accepted: 19 August 2021 / Published: 22 August 2021
(This article belongs to the Special Issue Molecular Biology of Age-Related Macular Degeneration (AMD) 2.0)
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. View Full-Text
Keywords: age-related macular degeneration; hydroquinone; oxidative stress; autophagy; ubiquitin-proteasome system (UPS); lysosomal alkalization age-related macular degeneration; hydroquinone; oxidative stress; autophagy; ubiquitin-proteasome system (UPS); lysosomal alkalization
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MDPI and ACS Style

Abokyi, S.; Shan, S.-W.; Lam, C.H.-I.; Catral, K.P.; Pan, F.; Chan, H.H.-L.; To, C.-H.; Tse, D.Y.-Y. Targeting Lysosomes to Reverse Hydroquinone-Induced Autophagy Defects and Oxidative Damage in Human Retinal Pigment Epithelial Cells. Int. J. Mol. Sci. 2021, 22, 9042. https://doi.org/10.3390/ijms22169042

AMA Style

Abokyi S, Shan S-W, Lam CH-I, Catral KP, Pan F, Chan HH-L, To C-H, Tse DY-Y. Targeting Lysosomes to Reverse Hydroquinone-Induced Autophagy Defects and Oxidative Damage in Human Retinal Pigment Epithelial Cells. International Journal of Molecular Sciences. 2021; 22(16):9042. https://doi.org/10.3390/ijms22169042

Chicago/Turabian Style

Abokyi, Samuel, Sze-Wan Shan, Christie Hang-I Lam, Kirk Patrick Catral, Feng Pan, Henry Ho-Lung Chan, Chi-Ho To, and Dennis Yan-Yin Tse. 2021. "Targeting Lysosomes to Reverse Hydroquinone-Induced Autophagy Defects and Oxidative Damage in Human Retinal Pigment Epithelial Cells" International Journal of Molecular Sciences 22, no. 16: 9042. https://doi.org/10.3390/ijms22169042

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