Synaptic repair and vision restoration in advanced degenerating eyes by transplantation of retinal progenitor cells

Summary Stem cell transplantation shows enormous potential for treatment of incurable retinal degeneration (RD). To determine if and how grafts connect with the neural circuits of the advanced degenerative retina (ADR) and improve vision, we perform calcium imaging of GCaMP5-positive grafts in retinal slices. The organoid-derived C-Kit+/SSEA1− (C-Kit+) retinal progenitor cells (RPCs) become synaptically organized and build spontaneously active synaptic networks in three major layers of ADR. Light stimulation of the host photoreceptors elicits distinct neuronal responses throughout the graft RPCs. The graft RPCs and their differentiated offspring cells in inner nuclear layer synchronize their activities with the host cells and exhibit presynaptic calcium flux patterns that resemble intact retinal neurons. Once graft-to-host network is established, progressive vision loss is stabilized while control eyes continually lose vision. Therefore, transplantation of organoid-derived C-Kit+ RPCs can form functional synaptic networks within ADR and it holds promising avenue for advanced RD treatment.
Highlights •C-Kit+ RPCs migrate and integrate in 3 major layers of advanced degenerative retina • Host inputs evoked by light activates graft neural response • 2-photon imaging visually defines graft-to-host synaptic Ca2+ transients in retina • Grafts connecting with the host retinal circuits preserves vision
In this article Liu, Yin, and colleagues show C-Kit+ retinal progenitor cells can migrate and integrate in three major layers of advanced degenerative retina, form functional synapses with the hosts, and connect with the neural circuits. They provide state-of-the-art techniques to visually demonstrate exceptional synaptic repair and vision restoration, opening up a feasible avenue for advanced RD treatment.