The retinal explant as a model to investigate neuronal pathology and neuroprotective strategies

Doctoral thesis English OPEN
Binley, Kate E.
  • Subject: RE

Despite the association of neuronal cell loss with a wide range of neurodegenerative disorders, the mechanisms leading to this cell death remain poorly understood. In this thesis I have investigated these mechanisms and tested whether they represent viable targets for therapeutic intervention. The adult mouse retinal explant is a popular model of axotomy-induced neuronal degeneration but has been limited by the lack of morphometric data. Since dendritic pruning is well-evidenced to precede cell loss in neurodegenerative diseases, including glaucoma and Alzheimer’s disease, I investigated whether the quantification of dendritic morphology of retinal ganglion cells in the retinal explant could be used as a more sensitive measure of neuronal health after axotomy. I report here that retinal ganglion cell dendrite loss precedes cell loss by at least 7 days and that this retraction is substantially retarded following treatment with brain-derived neurotrophic factor applied at the time of explantation. Perhaps most importantly, I demonstrate for the first time in this model that delayed application of brain-derived neurotrophic factor significantly protects against dendritic retraction of retinal ganglion cells. The work outlined in this thesis thus supports the targeting of dendritic outgrowth and/or synaptic connectivity for the treatment of neurodegenerative disorders.
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