Electrophysiological Analysis of Retinal Organoid Development Using 3D Microelectrodes of Liquid Metals

Area of Science:

• Neuroscience
• Developmental Biology
• Biomedical Engineering

Background:

• Human retinal organoids hold significant potential for studying retinal development and disease.
• Retinal ganglion cell (RGC) degeneration during organoid maturation limits functional assessment.
• Current analysis methods using fluorescence risk damaging organoid structure and offer limited functional insights.

Purpose of the Study:

• To develop and validate an electrophysiological method for monitoring RGC development in early to mid-stage human retinal organoids.
• To compare the functional properties and synaptic connectivity of RGCs in organoids with mature mouse retinas.
• To establish early-stage retinal organoids as a viable model for studying RGC function.

Main Methods:

• Utilized high-resolution 3D printing of soft liquid-metal microelectrodes for precise targeting within organoids.
• Performed electrophysiological recordings to monitor RGC development and activity.
• Compared organoid RGC electrophysiology and synaptic features with in vivo mature mouse retinas.

Main Results:

• Demonstrated the successful monitoring of RGC development and functional properties in early to mid-stage retinal organoids.
• Revealed insights into the synaptic connectivity of organoid RGCs, resembling fetal native retinas.
• Validated organoid features through comparison with mature mouse retina in vivo.

Conclusions:

• Electrophysiological analysis using 3D-printed microelectrodes is effective for assessing RGC function in retinal organoids.
• Early-stage retinal organoids exhibit functional and connectivity characteristics comparable to native fetal retinas.
• This approach enhances the utility of retinal organoids for biomedical research, particularly in studying RGCs.