|
|||||
|
|
Characterization of the retinal pigment epithelium in Friedreich ataxia |
|
| Authors: | Duncan E. Crombie Nicole Van Bergen Kathryn C. Davidson Sara Anjomani Virmouni Penny A. Mckelvie Vicki Chrysostomou Alison Conquest Louise A. Corben Mark A. Pook Tejal Kulkarni Ian A. Trounce Martin F. Pera Martin B. Delatycki Alice Pébay |
| Affiliation: | 1. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital & Department of Surgery, The University of Melbourne, East Melbourne, Australia;2. Division of Biosciences, Department of Life Sciences, College of Health & Life Sciences & Synthetic Biology Theme, Institute of Environment, Health & Societies, Brunel University London, Uxbridge, UK;3. St. Vincents Hospital, Fitzroy , Australia;4. Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville Victoria, Australia; Department of Paediatrics, The University of Melbourne, Australia;5. School of Psychological Sciences , Monash University, Clayton, Australia;6. Department of Anatomy and Neurosciences, The University of Melbourne, Florey Neuroscience and Mental Health Institute, Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia;7. Clinical Genetics, Austin Health, Heidelberg, Australia |
| Abstract: | We assessed structural elements of the retina in individuals with Friedreich ataxia (FRDA) and in mouse models of FRDA, as well as functions of the retinal pigment epithelium (RPE) in FRDA using induced pluripotent stem cells (iPSCs). We analyzed the retina of the FRDA mouse models YG22R and YG8R containing a human FRATAXIN (FXN) transgene by histology. We complemented this work with post-mortem evaluation of eyes from FRDA patients. Finally, we derived RPE cells from patient FRDA-iPSCs to assess oxidative phosphorylation (OXPHOS) and phagocytosis. We showed that whilst the YG22R and YG8R mouse models display elements of retinal degeneration, they do not recapitulate the loss of retinal ganglion cells (RGCs) found in the human disease. Further, RPE cells differentiated from human FRDA-iPSCs showed normal OXPHOS and we did not observe functional impairment of the RPE in Humans. |
| Keywords: | Friedreich ataxia Induced pluripotent stem cells Retinal pigment epithelium Human eye Mouse models Oxidative phosphorylation |
| 本文献已被 ScienceDirect 等数据库收录！ | |