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The role of retinal ganglion cell axons in the regulation of glial cell numbers in the rodent optic nerve

Burne, Julia F; (1997) The role of retinal ganglion cell axons in the regulation of glial cell numbers in the rodent optic nerve. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

The effect of increased optic nerve axon number on glial cell numbers was studied in a transgenic mouse that expresses the human bcl-2 gene from a neuron-specific-enolase promoter. The normal postnatal loss of retinal ganglion cell (RGC) axons was decreased and, consequently, the number of axons in the adult optic nerve was 80% greater. The expression of human Bcl-2 in RGCs protected the cell body from programmed cell death when the axon was cut, but it did not protect the isolated axon from Wallerian degeneration, even though human Bcl-2 was present in the axon. The numbers of both oligodendrocytes and astrocytes increased proportionally in the transgenic optic nerve. Unexpectedly, the transgene was expressed in both types of glia, but this was not responsible for the increased numbers of these cells. Oligodendrocytes increased because of a decrease in normal cell death, whereas astrocytes increased because of increased proliferation. To investigate whether astrocyte proliferation normally depends on axons I looked first at the effect of axon removal induced by Wallerian degeneration and found that this stopped astrocyte division. This was also the case in cut optic nerves in the Wlds mutant mouse where the axons did not degenerate. I found that axonal transport, but not electrical activity in the axons was required for axons to stimulate astrocyte division, suggesting that the putative astrocyte mitogen must be continuously transported from the cell body to the axon. I showed that purified RGCs can stimulate astrocytes to synthesise DNA when RGCs were co-cultured with a mixed population of optic nerve cells; of all the signalling molecules tested, only bFGF could mimic this effect of the RGCs. Finally I have found weak evidence that Wallerian degeneration of axons may utilise some of the proteases (caspases) that mediate programmed cell death.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The role of retinal ganglion cell axons in the regulation of glial cell numbers in the rodent optic nerve
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Optic nerve; Retinal ganglion cell
URI: https://discovery.ucl.ac.uk/id/eprint/10097978
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