Harnessing Astrocytes and Müller Glial Cells in the Retina for Survival and Regeneration of Retinal Ganglion Cells

Cells, 2021 · DOI: https://doi.org/10.3390/cells10061339 · Published: May 28, 2021

Simple Explanation

Astrocytes, typically seen as hindering nerve regeneration in the central nervous system due to scar formation, have shown promise in spinal cord injury recovery by becoming growth-supportive. This review explores whether astrocytes and Müller cells in the retina, which react to retinal and optic nerve damage, can be similarly induced to support retinal ganglion cell (RGC) survival and axon regeneration. The review identifies potential molecular pathways that induce growth-supportive astrocytes in the spinal cord. It suggests that activating these pathways in the retina could be a new therapeutic approach for promoting RGC survival and axon regeneration in retinal degenerative diseases. Epidermal Growth Factor (EGF) signaling in the spinal cord seems to induce the A2 phenotype, it is currently unknown whether EGFR signaling can also generate A2 astrocytes in the retina and promote RGC survival and axon regeneration after injury.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Astrocytes and Müller cells in the retina undergo reactive gliosis after damage, and their role in RGC survival and axon regeneration is debated.
2
Inducing growth-supportive astrocytes in the spinal cord has shown promise, suggesting a similar approach might benefit RGCs in retinal degenerative diseases.
3
Manipulating Epidermal Growth Factor (EGF) signaling in the spinal cord appears to aid CNS axon regeneration by inducing the A2 phenotype that can provide axon growth-supportive substrates.

Research Summary

This review discusses the potential of harnessing astrocytes and Müller glial cells in the retina to promote the survival and regeneration of retinal ganglion cells (RGCs). It draws parallels with studies in spinal cord injury (SCI), where astrocytes have been induced to become growth-supportive. The review highlights the dual role of astrocytes, traditionally seen as inhibitors of axon regeneration in the CNS but now recognized for their potential in neural repair. It explores the possibility of inducing a growth-supportive state in retinal macroglia to aid RGC survival and axon regeneration. The authors suggest that stimulating specific molecular pathways, particularly those involved in inducing growth-supportive astrocytes in the spinal cord, could represent a novel therapeutic approach for retinal degenerative diseases. They also note the need for further research to elucidate the reparative roles of retinal gliosis.

Practical Implications

Therapeutic Potential

Stimulating specific molecular pathways in retinal macroglia could lead to new treatments for retinal degenerative diseases.

Further Research

More research is needed to understand the reparative roles of retinal gliosis and the effects of EGFR ligand-induced EGFR signaling on RGC survival and axon regeneration.

Drug Delivery

Future research should evaluate the efficacy of EGFR ligand-based eye drops after ONC.

Study Limitations

1
The exact mechanisms by which astrocytes and Müller cells can be induced to become growth-supportive in the retina are not fully understood.
2
The phenotypic dichotomy of reactive Müller cells has yet to be defined.
3
Whether so-called neurotoxic astrocytes are indeed detrimental to neurons.

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