Injury to optic nerve (ON) axons plays a major role in glaucoma progression. ON crush is an established model of axonal injury which results in retrograde degeneration and death of retinal ganglion cells (RGCs). However, it is unknown how signal transmission to higher visual structures such as primary visual cortex (V1) is affected after ON crush. In human glaucoma, visual function is assessed using visual field (VF) tests, but it is also not clear how the test results relate to the disease progression in the retina. Unilateral ON crush was performed on the left eyes of adult C57BL/6 mice. V1 function of the right hemisphere was assessed longitudinally by optical imaging (OI) and in vivo calcium two-photon imaging under anaesthesia before and at 7 days, 14 days and 30 days after ON crush. Human retinas from glaucoma patients were investigated for changes in RGC density and compared to the score from the VF data obtained prior to the patients’ death. ISI and 2P experiments demonstrate a significant shift in OD towards the ipsilateral eye and significant reduction of signal magnitude in V1 in response to contralateral eye stimulation in all ON crush animals. Additionally, response magnitude to ipsilateral eye stimulation was significantly increased after ON crush. While there was significant RGC loss in human glaucoma compared to age matched controls that was correlated to mean VF loss, the scores from the individual VF test points were uncorrelated to RGC density in anatomically equivalent areas. This work demonstrates that unilateral ON crush results in immediate loss of signal transmission from the retina to V1 via a crushed ON. A significant increase of responsiveness in V1 to non-crushed eye stimulation was observed, which indicates that injury of the ON in adulthood may evoke compensatory plasticity in V1.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:704941 |
| Date | January 2016 |
| Creators | Vasalauskaite, Asta |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/98604/ |
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