Table 1.
Summary of studies that assessed the effect of PTEN silencing on axon regeneration and neuronal survival in the corticospinal tract and optic nerve
| Method for PTEN silencing | Injury model | Age of mice: PTEN deletion | Age of mice: Injury | Main findings regarding axon regeneration | Reference |
|---|---|---|---|---|---|
| Transgenic | Optic nerve crush | Postneonatal 3 wk | Young adult 5 wk | - Increased RGC survival by 2-fold - Axon regeneration up to 4 mm beyond the crush site at 4 wk post-injury |
Park et al., 2008 |
| Postneonatal 3 wk | Young adult 5 wk | - Increased RGC survival by 2-fold - Axon regeneration up to 3 mm beyond the crush site at 4 wk post-injury |
Sun et al., 2011 | ||
| Young adult 5 wk | Young adult 5 wk | - No effect on RGC survival xs- Axon regeneration up to 2.5 mm beyond the crush site at 3 wk post-injury |
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| Young adult 8–12 wk | Young adult/adult 10–14 wk | - Increased RGC survival by 3-fold - Axon regeneration up to 2.5 mm beyond the crush site at 3 wk post-injury |
Leibinger et al., 2016 | ||
| Young adult 8–12 wk | Young adult/adult 11–15 wk | - Increased RGC survival by 2-fold - Axon regeneration up to 3 mm beyond the crush site at 3 wk post-injury |
Leibinger et al., 2019 | ||
| T8 crush | Neonatal 1 d | Young adult 6 wk | Axon regeneration up to 2.5 mm at 12 wk post-injury | Liu et al., 2010 | |
| Young adult 4 wk | Young adult8 wk | Axon regeneration up to 1.5 mm at 12 wk post-injury | |||
| Adult 12 wk | Young adult 8 wk | Axon regeneration up to 2.5 mm beyond the lesion at 16 wk after PTEN deletion | Du et al., 2015 | ||
| Aged 1 yr and 2 mon | Young adult 8 wk | - Axon regeneration up to 1.5 mm beyond the lesion at 4 mon after PTEN deletion - Axon regeneration up to 3 mm beyond the lesion at 7 mon after PTEN deletion | |||
| Neonatal 1 d | Young adult 7 wk | - Axon regeneration up to 1.5 mm beyond the lesion at 8 wk post-injury - Improved hindlimb function | Leibinger et al., 2021 | ||
| T8 dorsal hemisection | Neonatal 1 d | Young adult 6 wk | Axon regeneration up to 1.5 mm beyond the lesion at 8 wk post-injury | Liu et al., 2010 | |
| Neonatal 1 d | Young adult 6 wk | - Axon regeneration up to 1.5 mm beyond the lesion at 6 wk post-injury - No effect on hindlimb function |
Geoffroy et al., 2015 | ||
| Young adult 4–6 wk | Young adult 8–10 wk | - Axon regeneration up to 1.0 mm beyond the lesion at 6 wk post-injury - No effect on hindlimb function |
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| Neonatal 1 d | Young adult 4–6 wk | Axon regeneration up to 1.5 mm beyond the lesion at 6 wk post-injury | Geoffroy et al., 2016 | ||
| Young adult 4–6 wk | Young adult 8–12 wk | Axon regeneration up to 0.75 mm beyond the lesion at 6 wk post-injury | |||
| Young adult 10 wk | Adult 14–16 wk | Axon regeneration up to 0.25 mm beyond the lesion at 6 wk post-injury | |||
| Aged 12–18 mon | Aged 13–20 mon | No axon regeneration beyond the lesion at 6 wk post-injury | |||
| C5 contusion | Young adult 7–9 wk | Young adult 7–9 wk | - Axon regeneration up to 2 mm beyond the contusion site at 16 wk post-injury - Improved forelimb function |
Danilov and Steward, 2015 | |
| AAV-shRNA | T8 crush | Neonatal 1 d | Young adult 7–8 wk | Axon regeneration up to 1.5 mm beyond the crush at 8 wk post-injury | Zukor et al., 2013 |
| Optic nerve crush | Young adult 4–6 wk | Young adult 6–8 wk | - Increased RGC survival by 2-fold - Axon regeneration up to 2 mm beyond the crush at 4 wk post-injury |
Yungher et al., 2015 |
This table highlights that PTEN silencing is a well-established approach to promote axon regeneration and that there is an age-depended decline of axon regeneration capacity. In addition to ageing, the different extensiveness of axon regeneration observed between studies are caused by variation in the injury models, and the techniques applied to silence PTEN such differences in the viral vector design, and other experimental paradigms differences. Transgenic codeletion and other growth-promoting treatments combined with genetic PTEN silencing are not included in this table. Studies that examined the effect of genetic PTEN silencing in other species than mice and those that examined effects on CNS sprouting, rubrospinal tract regeneration, or peripheral nervous system regeneration, are not included in this table. The number of regenerating axonal fibres is not included in this table due to differences in the quantification method per study. RGC: retinal ganglion cell.