Testing Mitochondrial-Targeted Drugs in iPSC-RPE from Patients with Age-Related Macular Degeneration.

Autor: Ebeling MC; Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA., Geng Z; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA.; Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA., Stahl MR; Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA., Kapphahn RJ; Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA., Roehrich H; Histology Core for Vision Research, University of Minnesota, Minneapolis, MN 55455, USA., Montezuma SR; Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA., Ferrington DA; Department of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN 55455, USA.; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA., Dutton JR; Stem Cell Institute, University of Minnesota, Minneapolis, MN 55455, USA.; Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2022 Jan 04; Vol. 15 (1). Date of Electronic Publication: 2022 Jan 04.
DOI: 10.3390/ph15010062
Abstrakt: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. No universally effective treatments exist for atrophic or "dry" AMD, which results from loss of the retinal pigment epithelium (RPE) and photoreceptors and accounts for ≈80% of all AMD patients. Prior studies provide evidence for the involvement of mitochondrial dysfunction in AMD pathology. This study used induced pluripotent stem cell (iPSC) RPE derived from five AMD patients to test the efficacy of three drugs (AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide), Metformin, trehalose) that target key processes in maintaining optimal mitochondrial function. The patient iPSC-RPE lines were used in a proof-of-concept drug screen, utilizing an analysis of RPE mitochondrial function following acute and extended drug exposure. Results show considerable variability in drug response across patient cell lines, supporting the need for a personalized medicine approach for treating AMD. Furthermore, our results demonstrate the feasibility of using iPSC-RPE from AMD patients to develop a personalized drug treatment regime and provide a roadmap for the future clinical management of AMD.
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje