Article Alert: A Step Closer to hPSC-based Therapies for Retinal Degenerative Disease

Efforts to restore vision impacted by retinal degenerative diseases (RDD) (e.g., retinitis pigmentosa and glaucoma) have focused on either exogenous replacement of essential cell types (i.e., photoreceptors and retinal ganglion cells (RGCs)) or “repurposing” of other associated cells. This is due to the inability of the mammalian retina to replace lost neurons. However, the success of either vision restorative strategy is dependent ultimately on new synaptic circuits being established by donor/regenerated retinal neurons. Recent work by Ludwig et al. makes a significant contribution to realizing the ambitious goal of replacement therapy for RDD (1).

In their study, the authors utilize a clever in vitro, rabies virus-based, monosynaptic retrograde tracing assay to recognize new synaptic connections among early retinal cell types from dissociated human pluripotent stem cell (hPSC)-derived retinal organoids (RO). They found that the key retinal cells required for retinal cell reconstitution, specifically photoreceptors and RGCs, represented the primary neuronal populations among the traced presynaptic cells. The researchers’ system offers a potential framework for studying synaptic connectivity in cultured retinal neurons as well as for evaluating strategies to promote synaptogenesis. In addition, they provide further evidence that RO-derived retinal neurons are capable of the synaptic plasticity essential for visual circuit reintegration.

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