Characterization of dendritic changes induced by elevated intraocular pressure in a chronic glaucoma model.
Doctoral thesis, UCL (University College London).
Visual information is sent from the retina to central visual targets through the optic nerve which is formed of retinal ganglion cells’ (RGCs) axons. In rodents, the superior colliculus (SC) is the major site of termination of retinal axons and the lateral geniculate nucleus (LGN) is another target of retinal axons. Glaucoma is a progressive optic neuropathy, characterized by RGC death. Dendrites are fine neuronal processes which support postsynaptic contact elements and are responsible for receiving synaptic signals. Accordingly, the morphology of dendrites has a profound impact on integrating neuronal input to the central nervous system from peripheral targets. Previous studies have documented dendritic changes in neuronal degenerative processes including those occurring in ageing and diseases. However, the morphological changes of dendrites in the visual pathway in glaucoma have not been well characterized. This thesis characterizes morphological changes of dendrites in the retina and the central visual targets in an experimental rat model of glaucoma for the first time. Dendritic labelling was achieved using the fluorescent dye DiI with in vivo and in vitro techniques. Dendrites of neurons in the SC and LGN were labelled in vitro using 0.1% DiI solution, and those of the RGCs were labelled using the biolistic technique. Confocal microscopy was next performed to image neurons, and dendrites were traced and quantified using Image J. Dendritic parameters including the mean dendritic length and the number of dendrites per neuron were analyzed in baseline, glaucoma animals and age-matched controls. Dendritic morphologies were studied in five types of neurons in the SC (including horizontal (H); piriform (P); narrow field vertical (V); wide field vertical (W) and stellate (S) cells), two types of neurons in the LGN (including the relay neuron type I (LG1) and type II (LG2)) and three types of RGCs (including type I (RI), type II (RII) and type III (RIII)). In this thesis, both age-related and glaucoma-related dendritic changes were demonstrated in the RGCs, SC cells and LGN cells in our rat model of experimental glaucoma. Firstly, the mean dendritic length and dendritic number of RGCs, SC cells and LGN cells were significantly reduced during ageing in normal animals, and more pronounced changes were observed in glaucoma animals. Secondly, significant dendritic shrinkage and losses were also shown in glaucoma animals compared with age-matched controls. Thirdly, the RGC was the first site to show dendritic changes following elevated IOP, but the most prominent changes were visible in the SC. The results in this study implicated that both the RGC and SC are potential sites for an early diagnosis strategy. Additionally, the glaucoma-related dendritic degeneration was demonstrated not only in the RGCs, but also in the SC and LGN, indicating that both the retina and the brain should be targeted when considering therapies for glaucoma. In conclusion, this thesis characterizes dendritic changes in the visual pathway in rats with chronic glaucoma, demonstrating that both ageing and elevated intraocular pressure (IOP) can affect dendritic morphology in the RGCs, SC cells and LGN cells. The findings in this study have contributed to the understanding of retinal and central neuronal degeneration in glaucoma, providing new insights into potential diagnosis and therapeutic strategies.
|Title:||Characterization of dendritic changes induced by elevated intraocular pressure in a chronic glaucoma model|
|Open access status:||An open access version is available from UCL Discovery|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology > Institute of Ophthalmology - Visual Neuroscience|
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