Transplanted human induced pluripotent stem cells- derived retinal ganglion cells embed within mouse retinas and are electrophysiologically functional

Vrathasha Vrathasha; Sergei Nikonov; Brent Allen Bell; Jie He; Yajat Bungatavula; Katherine Elizabeth Uyhazi; Venkata Ramana Murthy Chavali

doi:10.1016/j.isci.2022.105308

Transplanted human induced pluripotent stem cells- derived retinal ganglion cells embed within mouse retinas and are electrophysiologically functional

iScience. 2022 Oct 7;25(11):105308. doi: 10.1016/j.isci.2022.105308. eCollection 2022 Nov 18.

Authors

Vrathasha Vrathasha¹, Sergei Nikonov^{1

2}, Brent Allen Bell^{1

2}, Jie He¹, Yajat Bungatavula¹, Katherine Elizabeth Uyhazi^{1

2}, Venkata Ramana Murthy Chavali^{1

2}

Affiliations

¹ Scheie Eye Institute at The Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
² Center for Advanced Retinal and Ocular Therapeutics (CAROT) and F.M. Kirby Center for Molecular Ophthalmology, University of Pennsylvania, Philadelphia, PA 19104, USA.

Abstract

Glaucoma is an optic neuropathy characterized by permanent visual field loss caused by the death of retinal ganglion cells (RGCs) and it is the leading cause of irreversible blindness worldwide. Consequently, there is an unmet need for the development of new strategies for its treatment. We investigated RGC replacement therapy as a treatment for ganglion cell loss. Human-induced pluripotent stem cells (hiPSCs) were differentiated into mature, functional RGCs in vitro, labeled with AAV2.7m8-SNCG-eGFP, and transplanted intravitreally in wild-type 4-month-old C57BL/6J mice. Survival of the transplanted hiPSC-RGCs was assessed by color fundus photography and histological studies confirmed the localization of the transplanted hiPSC-RGCs within the retina. Two-photon live imaging of retinal explants and electrophysiological studies confirmed that the morphology and function of the transplanted hiPSC-RGCs were similar to native RGCs. These experiments will provide key strategies to enhance the efficiency of stem cell replacement therapy for neurodegenerative diseases, including glaucoma.

Keywords: Bioengineering; Biological sciences; Biotechnology; Cell biology; Stem cells research; Tissue engineering.

Grants and funding

P30 EY001583/EY/NEI NIH HHS/United States