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TRAP1 Is Expressed in Human Retinal Pigment Epithelial Cells and Is Required to Maintain their Energetic Status.

Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University Coimbra, 3000-548 Coimbra, Portugal. Center for Innovative Biomedicine and Biotechnology (CIBB), University Coimbra, 3004-504 Coimbra, Portugal. Clinical Academic Center of Coimbra (CACC), 3000-548 Coimbra, Portugal. Faculty of Sciences and Technology, University Coimbra, 3030-790 Coimbra, Portugal. CNC-Center for Neuroscience and Cell Biology, University of Coimbra, UC Biotech, Parque Tecnológico de Cantanhede, 3060-197 Coimbra, Portugal. Department of Biomedical Engineering, The Fu Foundation School of Engineering and Applied Science, Columbia University, New York, NY 10027, USA. Department of Ophthalmology, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA. Faculty of Medicine, University Coimbra, 3000-370 Coimbra, Portugal. Jonas Children's Vision Care, and Bernard and Shirlee Brown Glaucoma Laboratory, Columbia Stem Cell Initiative, Pathology and Cell Biology, Institute of Human Nutrition, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. Association for Innovation and Biomedical Research on Light and Image (AIBILI), 3000-548 Coimbra, Portugal. Institute of Pharmacology and Experimental Therapeutics, Faculty of Medicine, University Coimbra, 3000-548 Coimbra, Portugal. Department of Life Sciences, University Coimbra, 3000-456 Coimbra, Portugal.

Antioxidants (Basel, Switzerland). 2023;(2)
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Abstract

Age-related macular degeneration (AMD) is the leading cause of severe vision loss and blindness in elderly people worldwide. The damage to the retinal pigment epithelium (RPE) triggered by oxidative stress plays a central role in the onset and progression of AMD and results from the excessive accumulation of reactive oxygen species (ROS) produced mainly by mitochondria. Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial molecular chaperone that contributes to the maintenance of mitochondrial integrity by decreasing the production and accumulation of ROS. The present study aimed to evaluate the presence and the role of TRAP1 in the RPE. Here, we report that TRAP1 is expressed in human adult retinal pigment epithelial cells and is located mainly in the mitochondria. Exposure of RPE cells to hydrogen peroxide decreases the levels of TRAP1. Furthermore, TRAP1 silencing increases intracellular ROS production and decreases mitochondrial respiratory capacity without affecting cell proliferation. Together, these findings offer novel insights into TRAP1 functions in RPE cells, opening possibilities to develop new treatment options for AMD.