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of retinal pigment epithelium (RPE) and photoreceptors and is one of the leading causes of blindness in the elderly. Oxidative damage to proteins, lipids, and DNA has been associated with RPE dysfunction and AMD. In this study, we evaluated oxidative stress in AMD and the efficacy of antioxidant, N-acetyl-L-cysteine (NAC), in protecting RPE from oxidative damage. To test this idea, primary cultures of RPE from human donors with AMD (\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                      <mml:mi>n<\/mml:mi>\n                      <mml:mo>=<\/mml:mo>\n                      <mml:mn>32<\/mml:mn>\n                    <\/mml:math>\n                    ) or without AMD (No AMD,\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                      <mml:mi>n<\/mml:mi>\n                      <mml:mo>=<\/mml:mo>\n                      <mml:mn>21<\/mml:mn>\n                    <\/mml:math>\n                    ) were examined for expression of NADPH oxidase (NOX) genes, a source of reactive oxygen species (ROS). Additionally, the cells were pretreated with NAC for 2 hours and then treated with either hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ) or\n                    <jats:italic>tert<\/jats:italic>\n                    -butyl hydroperoxide (\n                    <jats:italic>t<\/jats:italic>\n                    -BHP) to induce cellular oxidation. Twenty-four hours after treatment, ROS production, cell survival, the content of glutathione (GSH) and adenosine triphosphate (ATP), and cellular bioenergetics were measured. We found increased expression of p22phox, a NOX regulator, in AMD cells compared to No AMD cells (\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M3\">\n                      <mml:mi>p<\/mml:mi>\n                      <mml:mo>=<\/mml:mo>\n                      <mml:mn>0.02<\/mml:mn>\n                    <\/mml:math>\n                    ). In both AMD and No AMD cells, NAC pretreatment reduced\n                    <jats:italic>t<\/jats:italic>\n                    -BHP-induced ROS production and protected from H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -induced cell death and ATP depletion. In the absence of oxidation, NAC treatment improved mitochondrial function in both groups (\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M4\">\n                      <mml:mi>p<\/mml:mi>\n                      <mml:mo>&lt;<\/mml:mo>\n                      <mml:mn>0.01<\/mml:mn>\n                    <\/mml:math>\n                    ). Conversely, the protective response exhibited by NAC was disease-dependent for some parameters. In the absence of oxidation, NAC significantly reduced ROS production (\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M5\">\n                      <mml:mi>p<\/mml:mi>\n                      <mml:mo>&lt;<\/mml:mo>\n                      <mml:mn>0.001<\/mml:mn>\n                    <\/mml:math>\n                    ) and increased GSH content (\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M6\">\n                      <mml:mi>p<\/mml:mi>\n                      <mml:mo>=<\/mml:mo>\n                      <mml:mn>0.02<\/mml:mn>\n                    <\/mml:math>\n                    ) only in RPE from AMD donors. Additionally, NAC-mediated protection from H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -induced GSH depletion (\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M7\">\n                      <mml:mi>p<\/mml:mi>\n                      <mml:mo>=<\/mml:mo>\n                      <mml:mn>0.04<\/mml:mn>\n                    <\/mml:math>\n                    ) and mitochondrial dysfunction (\n                    <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M8\">\n                      <mml:mi>p<\/mml:mi>\n                      <mml:mo>&lt;<\/mml:mo>\n                      <mml:mn>0.05<\/mml:mn>\n                    <\/mml:math>\n                    ) was more pronounced in AMD cells compared with No AMD cells. These results demonstrate the therapeutic benefit of NAC by mitigating oxidative damage in RPE. Additionally, the favorable outcomes observed for AMD RPE support NAC\u2019s relevance and the potential therapeutic value in treating AMD.\n                  <\/jats:p>","DOI":"10.1155\/2019\/5174957","type":"journal-article","created":{"date-parts":[[2019,8,14]],"date-time":"2019-08-14T19:31:14Z","timestamp":1565811074000},"page":"1-14","source":"Crossref","is-referenced-by-count":58,"title":["N-Acetyl-L-cysteine Protects Human Retinal Pigment Epithelial Cells from Oxidative Damage: Implications for Age-Related Macular Degeneration"],"prefix":"10.1155","volume":"2019","author":[{"given":"Marcia R.","family":"Terluk","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, Minnesota, USA"},{"name":"Center for Orphan Drug Research, Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara 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