Imaging Transplanted Photoreceptors in Living Nonhuman Primates with Single-Cell Resolution.

PubMed ID: 32707075

Author(s): Aboualizadeh E, Phillips MJ, McGregor JE, DiLoreto DA Jr, Strazzeri JM, Dhakal KR, Bateman B, Jager LD, Nilles KL, Stuedemann SA, Ludwig AL, Hunter JJ, Merigan WH, Gamm DM, Williams DR. Imaging transplanted photoreceptors in living nonhuman primates with single-cell resolution. Stem Cell Reports. 2020 Aug 11;15(2):482-497. doi: 10.1016/j.stemcr.2020.06.019. Epub 2020 Jul 23. PMID 32707075

Journal: Stem Cell Reports, Volume 15, Issue 2, Aug 2020

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 ultrafast 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.