Journal
STEM CELL REPORTS
Volume 15, Issue 2, Pages 482-497Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2020.06.019
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Funding
- National Eye Institute of the NIH [U01 EY025497-Audacious, U54HD090256, P30 EY001319]
- Research to Prevent Blindness
- Retina Research Foundation Emmett A. Humble Directorship
- Sandra Lemke Trout Chair in Eye Research
- Muskingum County Community Foundation
- Carl Marshall Reeves and Mildred Almen Reeves Foundation
- NATIONAL EYE INSTITUTE [F30EY031230] Funding Source: NIH RePORTER
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Stem cell-based transplantation therapies offer hope for currently untreatable retinal degenerations; however, preclinical progress has been largely confined to rodent models. Here, we describe an experimental platform for accelerating photoreceptor replacement therapy in the nonhuman primate, which has a visual system much more similar to the human. We deployed fluorescence adaptive optics scanning light ophthalmoscopy (FAOSLO) to noninvasively track transplanted photoreceptor precursors over time at cellular resolution in the living macaque. Fluorescently labeled photoreceptors generated from a CRX+/tdTomato human embryonic stem cell (hESC) reporter line were delivered subretinally to macaques with normal retinas and following selective ablation of host photoreceptors using an ultra-fast laser. The fluorescent reporter together with FAOSLO allowed transplanted photoreceptor precursor survival, migration, and neurite formation to be monitored over time in vivo. Histological examination suggested migration of photoreceptor precursors to the outer plexiform layer and potential synapse formation in ablated areas in the macaque eye.
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