Zebrafish optic nerve regeneration involves resident and retinal oligodendrocytes

Area of Science:

• Neuroscience
• Developmental Biology
• Regenerative Medicine

Background:

• The visual system of teleost fish offers a model for central nervous system regeneration due to continuous growth.
• Oligodendrocytes are crucial glial cells in this process, but their precise role in optic nerve regeneration remains unclear.

Purpose of the Study:

• To investigate the dynamic changes and roles of oligodendrocytes during zebrafish optic nerve regeneration.
• To understand the contribution of oligodendrocyte progenitor cells to the regenerative process.

Main Methods:

• Utilized the sox10:tagRFP transgenic zebrafish line and confocal microscopy to track oligodendrocytes.
• Employed Sox2 immunohistochemistry to identify oligodendrocyte progenitor cells and assess differentiation.
• Applied Click-iT™ Plus TUNEL assay for cell death and BrdU assay for cell proliferation analysis.

Main Results:

• Oligodendrocytes (sox10:tagRFP+) initially disappeared from the optic nerve crush site, suggesting degeneration, but were not TUNEL-positive.
• Sox2-positive cells, indicative of progenitor cells, increased around the lesion, optic nerve head, and retina.
• Double-positive sox10:tagRFP /Sox2 cells and proliferation were observed between 24 hours and 14 days post-lesion, indicating progenitor cell activation and differentiation.

Conclusions:

• Oligodendrocytes undergo a degeneration phase before regeneration, transitioning from myelinating to non-myelinating forms and eventually dying.
• Oligodendrocyte progenitor cells in the optic nerve and retina proliferate and differentiate to remyelinate new axons.
• Oligodendrocytes actively participate in zebrafish axon regeneration by guiding, nourishing, and myelinating newly formed axons.