A Human Retinal Pigment Epithelium-Based Screening Platform Reveals Inducers of Photoreceptor Outer Segments Phagocytosis
Year: 2020
Type: article
Abstract: Phagocytosis is a key function in various cells throughout the body. A deficiency in photoreceptor outer segment (POS) phagocytosis by the retinal pigment epithelium (RPE) causes vision loss in inherited retinal diseases and possibly age-related macular degeneration. To date, there are no effective therapies available aiming at recovering the lost phagocytosis function. Here, we developed a high-throughput screening assay based on RPE derived from human embryonic stem cells (hRPE) to reveal enhancers of POS phagocytosis. One of the hits, ramoplanin (RM), reproducibly enhanced POS phagocytosis and ensheathment in hRPE, and enhanced the expression of proteins known to regulate membrane dynamics and ensheathment in other cell systems. Additionally, RM rescued POS internalization defect in Mer receptor tyrosine kinase (MERTK) mutant hRPE, derived from retinitis pigmentosa patient induced pluripotent stem cells. Our platform, including a primary phenotypic screening phagocytosis assay together with orthogonal assays, establishes a basis for RPE-based therapy discovery aiming at a broad patient spectrum.
Source: Stem Cell Reports
Institutions: Center for Regenerative Therapies Dresden, Center for Molecular and Cellular Bioengineering, Technische Universität Dresden, Max Planck Institute of Molecular Cell Biology and Genetics, Columbia University Irving Medical Center, German Center for Neurodegenerative Diseases (DZNE) Dresden, Research Institute of Molecular Pathology, Vienna Biocenter
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,800
Funders: Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Technische Universität Dresden, Sächsisches Staatsministerium für Wissenschaft und Kunst, Zentrum für Regenerative Therapien Dresden, Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie, Exzellenzcluster Ozean der Zukunft, National Institutes of Health, National Eye Institute
OpenAlex ID: W3110310198