Q&A Report: Postsynaptic Neuronal Activity Promotes Retinal Axon Regeneration

Supraja Varadarajan, PhD answers questions from a recent webinar hosted by Striatech, “Postsynaptic Neuronal Activity Promotes Retinal Axon Regeneration”.

The answers to these questions have been provided by:

Supraja Varadarajan, PhD
Incoming Assistant Professor
University of Texas Southwestern Medical Center

You may also read this Q&A here: https://stria.tech/journal-club-postsynaptic-neuronal-activity-promotes-retinal-axon-regeneration/#QandA

Could you elaborate on the uniqueness of the distal injury model? How could it be used to study other diseases or conditions?

The distal injury is different from the optic nerve crush as the lesion site is caudal to the chiasm, not as severe, and RGC axons retain collaterals in some visual targets anterior to the lesion. These conditions cause degeneration in some RGCs therefore mimicking injuries that occur in clinical settings, as well as other degenerative optic neuropathies.

Have you looked at how individual retinal ganglion cell (RGC) subtypes may be affected in this injury model?

We haven’t yet looked at how different RGC subtypes are uniquely affected.

If all RGCs would die from the injury, how long would the green staining remain visible in the target areas?

In the CNS, degenerating processes should be cleared between 30-90 days.

Why are the spared axons spared?

The injury is a partial injury that severs some axons while other axons remain connected, i.e. spared.

Would increasing activity in postsynaptic neurons promote regeneration in an optic nerve crush model?

We haven’t tested this yet.

Have you looked at pattern ERG as a functional readout?


Since neighboring targets are innervated as well, this suggests that activity sets up a regenerative environment, and that it is not required for reconnecting?

It does indicate that activity promotes regeneration, but the current data does not test the role of activity in regeneration vs reconnection.

Can you identify if the regeneration you observe is coming from spared axons sprouting collaterals or are they from injured axons?

Yes retrograde labeling shows that there is a threefold increase in the number of RGCs labeled in the retina in the activity group compared to controls, indicating that injured axons are regenerating. However in addition to injured axons regenerating, spared axons are likely to be sprouting collaterals.

Since all injuries are not the same, and inflammation plays a major role in the repair process, which way the immune system may be playing a role, particularly in diseases?

We haven’t looked at the role of immune cells in our model yet.

What would be the most common normal injury or disease a patient might have that resembles the distal injury model?

Glaucoma and other degenerative diseases where some RGC axons degenerate over time are likely to show similar pathologies.