• Hoi Ching Suen, Yan Qian, Jinyue Liao, Chun Shui Luk, Wing Tung Lee, Judy Kin Wing Ng, Thomas Ting Hei Chan, Hei Wan Hou, Ingrid Li, Kit Li, Wai-Yee Chan, Bo Feng, Lin Gao, Xiaohua Jiang, Yuen Hang Liu, John A Rudd, Robin Hobbs, Huayu Qi, NgTsz KinTKDepartment of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China., Heather Kayew Mak, Kai Shun Leung, and Tin-Lap Lee.
• School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
• Stem Cells Dev. 2019 Oct 15; 28 (20): 1365-1375.

AbstractGlaucoma is characterized by retinal ganglion cell (RGC) degeneration and is the second leading cause of blindness worldwide. However, current treatments such as eye drop or surgery have limitations and do not target the loss of RGC. Regenerative therapy using embryonic stem cells (ESCs) holds a promising option, but ethical concern hinders clinical applications on human subjects. In this study, we employed spermatogonial stem cells (SSCs) as an alternative source of ESCs for cell-based regenerative therapy in mouse glaucoma model. We generated functional RGCs from SSCs with a two-step protocol without applying viral transfection or chemical induction. SSCs were first dedifferentiated to embryonic stem-like cells (SSC-ESCs) that resemble ESCs in morphology, gene expression signatures, and stem cell properties. The SSC-ESCs then differentiated toward retinal lineages. We showed SSC-ESC-derived retinal cells expressed RGC-specific marker Brn3b and functioned as bona fide RGCs. To allow in vivo RGC tracing, Brn3b-EGFP reporter SSC-ESCs were generated and the derived RGCs were subsequently transplanted into the retina of glaucoma mouse models by intravitreal injection. We demonstrated that the transplanted RGCs could survive in host retina for at least 10 days after transplantation. SSC-ESC-derived RGCs can thus potentially be a novel alternative to replace the damaged RGCs in glaucomatous retina.

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