Imaging Light Responses of Foveal Ganglion Cells in the Living Macaque Eye

Abstract

The fovea dominates primate vision, and its anatomy and perceptual abilities are well studied, but its physiology has been little explored because of limitations of current physiological methods. In this study, we adapted a novel in vivo imaging method, originally developed in mouse retina, to explore foveal physiology in the macaque, which permits the repeated imaging of the functional response of many retinal ganglion cells (RGCs) simultaneously. A genetically encoded calcium indicator, G-CaMP5, was inserted into foveal RGCs, followed by calcium imaging of the displacement of foveal RGCs from their receptive fields, and their intensity-response functions. The spatial offset of foveal RGCs from their cone inputs makes this method especially appropriate for fovea by permitting imaging of RGC responses without excessive light adaptation of cones. This new method will permit the tracking of visual development, progression of retinal disease, or therapeutic interventions, such as insertion of visual prostheses.

Assessing retinal ganglion cell damage

“…Alternatively, genetically encoded calcium indicators can be administered with viral vectors, eliminating the need for transgenic animals. 60 The ability to detect changes in intracellular calcium of RGCs allows for an in vivo functional measure of assessing RGC damage.…”

A New Promoter Allows Optogenetic Vision Restoration with Enhanced Sensitivity in Macaque Retina

“…Results from our study will be highly valuable in guiding viral dose and promoter choice in further clinical development of this approach and other optogenetic approaches aimed at vision restoration. Furthermore, the retinal ganglion cell (RGC) promoter we describe here will benefit both basic research 32 and clinical gene therapies targeting RGCs. 33 …”

Adaptive Optics Ophthalmoscopy

“…Visualizing the GCs in living eyes has only been possible to date using extrinsic fluorophores. Using specially designed AOSLO systems, extrinsic fluorophores of various types have been employed to visualize ganglion cells in monkeys (G-CaMP3, (Yin et al 2014)), rats (eGFP, (Geng et al 2009)) and mice (G-CaMP3, (Yin et al 2013); YFP-expressing genetic strains for GCs (Geng et al 2012)). Two examples of GCs imaged in a YFP-expressing mouse are shown in Fig.…”

“…The only functional optical recording from inner retinal neurons using AO has relied on the use of a neural-activity-dependent fluorescent dyes (calcium indicators, G-CaMP3) in mice (Yin et al 2013) and in monkeys (Yin et al 2014). These fluorescent-based approaches are not yet ready for use in humans, but the accelerating development of effective viral-based cellular delivery systems for gene therapy and the possibility that these vectors may also be approved to carry fluorescent payloads means that these techniques may translate to human use sooner than we might have anticipated.…”