Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China; Corresponding author
Zhiyang Chen
Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China
Xiaoman Zhu
Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China
Qingjian Ou
Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China
Zhe Wang
Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China
Binxin Wu
Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China
Jing-Ying Xu
Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China
Caixia Jin
Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China
Furong Gao
Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China
Juan Wang
Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China
Jingfa Zhang
Department of Ophthalmology, Shanghai General Hospital (Shanghai First People’s Hospital), Shanghai Jiao Tong University, Shanghai 200080, China
Jieping Zhang
Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China
Lixia Lu
Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China; Corresponding author
Guo-Tong Xu
Department of Ophthalmology of Tongji Hospital and Laboratory of Clinical and Visual Sciences of Tongji Eye Institute, Tongji University School of Medicine, Shanghai 200065, China; Department of Physiology and Pharmacology, Tongji University School of Medicine, Shanghai 200092, China; The collaborative Innovation Center for Brain Science, Tongji University, Shanghai 200092, China; Corresponding author
Summary: The hostile microenvironment of the retina in patients with age-related macular degeneration (AMD) may trigger epithelial-to-mesenchymal transition (EMT) of grafted retinal pigment epithelial (RPE) cells, thus attenuating the therapeutic outcome. Here, we transformed human dedifferentiated induced pluripotent stem cell-derived RPE (iPSC-RPE) cells into induced RPE (iRPE) cells using a cocktail of four transcription factors (TFs)—CRX, MITF-A, NR2E1, and C-MYC. These critical TFs maintained the epithelial property of iRPE cells by regulating the expression of bmp7, forkhead box f2, lin7a, and pard6b, and conferred resistance to TGF-β-induced EMT in iRPE cells by targeting ppm1a. The iRPE cells with Tet-on system-regulated c-myc expression exhibited EMT resistance and better therapeutic function compared with iPSC-RPE cells in rat AMD model. Our study demonstrates that endowing RPE cells with anti-EMT property avoids the risk of EMT after cells are grafted into the subretinal space, and it may provide a suitable candidate for AMD treatment.
