Crombie Duncan E, Van Bergen Nicole, Davidson Kathryn C, Anjomani Virmouni Sara, Mckelvie Penny A, Chrysostomou Vicki, Conquest Alison, Corben Louise A, Pook Mark A, Kulkarni Tejal, Trounce Ian A, Pera Martin F, Delatycki Martin B, Pébay Alice
Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital & Department of Surgery, The University of Melbourne, East Melbourne, Australia.
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.
Biochem Biophys Rep. 2015 Sep 11;4:141-147. doi: 10.1016/j.bbrep.2015.09.003. eCollection 2015 Dec.
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.
我们评估了弗里德赖希共济失调（FRDA）患者以及FRDA小鼠模型的视网膜结构成分，并利用诱导多能干细胞（iPSC）研究了FRDA中视网膜色素上皮（RPE）的功能。我们通过组织学分析了含有人类弗里德赖希共济失调蛋白（FXN）转基因的FRDA小鼠模型YG22R和YG8R的视网膜。我们通过对FRDA患者的眼睛进行尸检评估来补充这项工作。最后，我们从患者的FRDA-iPSC中获得RPE细胞，以评估氧化磷酸化（OXPHOS）和吞噬作用。我们发现，虽然YG22R和YG8R小鼠模型表现出视网膜变性的特征，但它们并未重现人类疾病中发现的视网膜神经节细胞（RGC）丢失。此外，从人类FRDA-iPSC分化而来的RPE细胞显示出正常的氧化磷酸化，并且我们未观察到人类RPE的功能受损。
