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Human photoreceptors switch from autonomous axon extension to cell-mediated process pulling during synaptic marker
Sarah K Rempel1, Madalynn J Welch2, Allison L Ludwig3
1Department of Neuroscience, University of Wisconsin - Madison, Madison, WI 53706, USA; McPherson Eye Research Institute, University of Wisconsin - Madison, Madison, WI 53706, USA.
Cell Reports
|May 18, 2022
Summary
Human pluripotent stem cell-derived retinal organoids reveal that early photoreceptors extend axons autonomously. Later, photoreceptors lose this ability, requiring non-photoreceptor cells for axon growth, impacting cell therapy for blindness.
Area of Science:
- Neuroscience
- Developmental Biology
- Ophthalmology
Background:
- Photoreceptor (PR) cells are crucial for vision, and their degeneration causes incurable blindness.
- Understanding PR axon growth is vital for developing effective cell replacement therapies.
Purpose of the Study:
- To investigate the mechanisms of photoreceptor axon extension during development and regeneration using human retinal organoids.
- To identify factors influencing photoreceptor process extension in 2D and 3D cultures.
Main Methods:
- Generation of retinal organoids from human pluripotent stem cells.
- Microscopic analysis of photoreceptor axon extension and terminal dynamics.
- Biochemical analysis of actin filaments and synaptic proteins in photoreceptor terminals.
Main Results:
- Early-born photoreceptors exhibit autonomous axon extension via dynamic terminals.
- Aging photoreceptors (40-80 days) lose terminal dynamics in both 2D and 3D cultures.
- Late-born photoreceptors extend axons by process stretching, relying on attachment to motile non-PR cells.
- Immobile late-born photoreceptor terminals show reduced actin organization but increased synaptic proteins compared to early-born ones.
Conclusions:
- Photoreceptor axon extension mechanisms change with differentiation time.
- Loss of terminal dynamics in aged photoreceptors presents a challenge for cell transplantation.
- Findings provide insights into photoreceptor development and potential strategies for vision restoration therapies.
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