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

ABSTRACT: 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.

SUBMITTER: Aboualizadeh E

PROVIDER: S-EPMC7419740 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Aboualizadeh Ebrahim E Phillips M Joseph MJ McGregor Juliette E JE DiLoreto David A DA Strazzeri Jennifer M JM Dhakal Kamal R KR Bateman Brittany B Jager Lindsey D LD Nilles Kelsy L KL Stuedemann Sara A SA Ludwig Allison L AL Hunter Jennifer J JJ Merigan William H WH Gamm David M DM Williams David R DR

Stem cell reports 20200723 2

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 t ...[more]

PMID: 32707075

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Project description:To evaluate the feasibility of safely performing aqueous angiography in intact eyes of living nonhuman primates (NHPs) for evaluating aqueous humor outflow and segmental patterns.Cross-sectional, observational study.Six nonhuman primates.Aqueous angiography was performed in 6 nonhuman primates. After anesthesia, an anterior chamber (AC) maintainer was placed through a temporal 1-mm side-port wound. Indocyanine green (ICG; 0.4%) or 2.5% fluorescein was introduced (individually or in sequence) into the eye with a gravity-driven constant-pressure system. Aqueous angiography images were obtained with a Spectralis HRA+OCT (Heidelberg Engineering GmbH, Heidelberg, Germany) suspended over the NHP eye using a custom-designed surgical boom arm. Concurrent anterior segment optical coherence tomography (OCT) was performed on distally angiographically positive and negative regions.Angiographic patterns described by location, time-course, choice of tracer, and anterior-segment OCT.Aqueous angiography in the living NHP eye demonstrated mostly stable angiographic patterns. With multimodal imaging, angiographically positive signal co-localized with episcleral veins as identified by infrared imaging and intrascleral lumens, as demonstrated by anterior segment OCT. Sequential aqueous angiography in individual eyes with ICG followed by fluorescein showed similar angiographic patterns. A pulsatile nature of aqueous angiographic outflow was sometimes observed. Aqueous angiographic patterns could also dynamically change. In some instances, positive angiographic flow suddenly arose in regions previously without an angiographic signal. Alternatively, an angiographic signal could suddenly disappear from regions in which an angiographic signal was initially documented.Aqueous angiography in living NHPs demonstrated segmental and pulsatile patterns with a newly described ability to dynamically shift. These characteristics further the understanding of live aqueous humor outflow biology and may be useful in improving glaucoma surgeries aimed at trabecular meshwork bypass.

Dataset Information

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

Publications

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

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