Autosomal dominant optic atrophy (ADOA) is an inherited optic neuropathy due to mutation in the OPA1 gene. Patients present with bilateral optic nerve head pallor and loss of visual function. Patients also show a reduction in the P50:N95 ratio of the pattern electroretinogram (PERG) and thinning of the retinal nerve fibre layer (RNFL) and macula. In a mouse model of ADOA, previously generated in this laboratory, the defect first manifested as a dendritic pruning of RGCs, which appeared to be ON-centre specific. Electrophysiological evidence in both humans and the mutant mice showed a reduction in the photopic negative component (PhNR) of the brief flash electroretinogram (ERG). The separation of the photopic ERG into ON- and OFF-pathway components using long-duration monochromatic (red) flash on a rod suppressing blue background, provided an opportunity to assess ON- and OFF-RGC function in ADOA, which had not been previously investigated in humans. This study therefore aimed to assess the effect of ADOA on the red-on blue PhNR-ON and PhNR-OFF components to determine whether the PhNR-ON was a selective marker for ADOA. In this thesis, a protocol was developed for recording long duration red-on-blue PhNRs from the macula (focal) and entire retina (full-field). A comparison of the retinotopic characteristics of the PhNRs (brief and long-duration) with the N95 of the PERG and the distribution of RGCs in the retina showed that the PhNR was capable of assessing RGC function. Retinal function was then probed in twelve participants with ADOA and sixteen controls using focal and full-field long duration ERG, full-field brief flash ERG and PERG. Retinal structure was also assessed using optical coherence tomography. In conclusion, this thesis found that the PhNR-ON and PhNR-OFF amplitudes were equally affected with no evidence of a preferential ON-pathway loss.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:709570 |
| Date | January 2016 |
| Creators | Morny, Enyam Komla |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/98943/ |
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