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The incidence of AMD increases with age. Retinal pigment epithelial (RPE) cells maintain retinal homeostasis and support the functionality of photoreceptors. In the pathogenesis of AMD, the degeneration of the RPE cells precedes photoreceptor cell death. RPE cells are susceptible to oxidative stress, and chronic inflammation involving nucleotide\u2010binding domain, leucine\u2010rich repeat and pyrin domain 3 (NLRP3) inflammasome activation and impaired autophagy are challenges faced by aged RPE cells in AMD. There are two types of AMD, dry (85\u201390%) and wet (10\u201315%) disease forms. Choroidal neovascularization is typical for wet AMD, and anti\u2010vascular endothelial growth factor (anti\u2010VEGF) injections are used to prevent the progression of the disease but there is no curative treatment. There is no cure for the dry disease form, but antioxidants have been proposed as a potential treatment option.<\/jats:p><jats:p>Ageing is the most important risk factor of AMD, and tobacco smoke is the most important environmental risk factor that can be controlled. Hydroquinone is a cytotoxic, immunotoxic, carcinogenic and pro\u2010oxidative component of tobacco smoke. The aim of this PhD thesis was to study hydroquinone\u2010induced oxidative stress and NLRP3 inflammasome activation in human RPE cells (ARPE\u201019 cells). An age\u2010related eye disease study (AREDS) formulation (incl. omega\u20103 fatty acids, vitamin C and E, copper, zinc, lutein and zeaxanthin), which is clinically investigated p.o. dosing combination of dietary supplements for AMD patients, has been evaluated as a possible treatment and restraining option for AMD. Resvega (4.1.1, Table 2) is a similar kind of product to AREDS with added resveratrol, and many of the components incorporated within Resvega can be considered as belonging to the normal antioxidative defence system of the retina. Another aim was to evaluate the effects of Resvega on hydroquinone\u2010induced oxidative stress or NLRP3 inflammasome activation induced by impaired protein clearance.<\/jats:p><jats:p>The results of this study reveal that hydroquinone elevated the activity of NADPH oxidase which subsequently mediated the production of reactive oxygen species (ROS) and predisposed RPE cells to degeneration by reducing levels of vascular endothelial growth factor (VEGF) and pigment epithelium\u2010derived factor (PEDF). Hydroquinone induced an NLRP3\u2010independent IL\u201018 release and NLRP3 accumulation inside the IL\u20101\u03b1\u2010primed cells. Resvega treatment reduced the extent of hydroquinone\u2010induced ROS production and NLRP3 inflammasome activation evoked by impaired protein clearance. Thus, Resvega alleviated hydroquinone\u2010 and impaired protein clearance\u2010induced stress in human RPE cells, but more studies are needed, for example, to reveal the most optimal route of administration for targeting the cells in the retina, since both oxidative stress and NLRP3 inflammasome activation are important contributors to the development of AMD and represent significant treatment targets.<\/jats:p>","DOI":"10.1111\/aos.15275","type":"journal-article","created":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T01:01:18Z","timestamp":1667869278000},"page":"3-59","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Regulation of oxidative stress and inflammatory responses in human retinal pigment epithelial cells"],"prefix":"10.1111","volume":"100","author":[{"given":"Niina","family":"Harju","sequence":"first","affiliation":[{"name":"School of Pharmacy University of Eastern Finland Kuopio 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