The consequences for central nervous system synaptic transmission following retinal degeneration and its treatment.
Doctoral thesis, UCL (University College London).
Previous studies into glaucoma in animal models have concentrated on the retinal ganglion cell (RGC) degeneration associated with the disease. However it is of interest also to examine any changes that occur in the rest of the retina and visual system, including the brain areas associated with vision, to gain a better understanding of the disease and to have better knowledge for designing treatments. This study looks at two rat models of RGC degeneration which are currently used in our lab for treatment studies. These models are the Morrison method of glaucoma and a model where an intravitreal injection of Aβ1-42 oligomers is given to cause RGC apoptosis. To investigate functional changes in the visual system from the retina to the central visual areas of these animals we have employed electrophysiological techniques at different time points after model induction. Using electroretinography (ERG) and histology of the retina we found that the RGC degeneration in the OHT model of glaucoma is also accompanied by 16 weeks after surgery by a dysfunction of the outer retina. However in the Aβ oligomer model only the RGCs were affected in the retina by 16 weeks after injection. We also found changes in the synaptic transmission from the RGCs to the superior colliculus (SC) in both models using in vitro SC slice electrophysiology. This included changes in the group III metabotropic glutamate receptor (mGluR) modulation of synaptic transmission from the RGCs to the SC and NMDA receptor contribution to synaptic transmission in the SC. The results from this study suggest that it will be necessary in the future to study the mechanisms of changes in cells other than just the RGCs in the retina and changes that occur to the central visual areas due to RGC degeneration in greater detail. It has also highlighted the need for the development of neuroprotective strategies and has added further importance for studies looking at earlier changes in and diagnosis of diseases where RGC degeneration is involved.
|Title:||The consequences for central nervous system synaptic transmission following retinal degeneration and its treatment|
|Additional information:||Authorisation for digitisation not received|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology|
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