Understanding axon regeneration and retinal ganglion cell neuroprotection in optic nerve injury

Thompson, Adam (2019). Understanding axon regeneration and retinal ganglion cell neuroprotection in optic nerve injury. University of Birmingham. Ph.D.

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Abstract

Most central nervous system (CNS) axons are incapable of regenerating after injury and their cell bodies die by apoptosis. A glial scar forms at the injury site and acts as a physical and chemical barrier to regenerating axons. It is frequently observed that no scar is formed when axons are experimentally stimulated to regenerate. Here, we attempted to test the hypothesis that given robust regenerative stimulation, CNS axons can grow through and degrade an established mature glial scar in an optic nerve crush (ONC) model of CNS injury. First in vivo and ex vivo methods of assessing retinal ganglion cell (RGC) survival were compared. Acute phase bone morphogenetic protein 4 (BMP4) therapy was tested as a potential pro-regenerative treatment. Finally, axogenic treatment was delayed until after a mature glial scar had established to test the initial hypothesis. RNA Binding Protein, mRNA Processing Factor (RBPMS) counts on retinal sections were determined to be the optimal method of assessing RGC survival, alongside longitudinal in vivo assessment of retinal nerve fibre layer (RNFL) thickness. BMP4 treatment promoted RGC survival but not axonal regeneration. In the final study after ONC and delayed axogenic treatment, no glial scar degradation or RGC axon regeneration was observed.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):