Mutations in OPA1 are the leading cause of autosomal dominant optic atrophy, a disease in which a progressive loss of retinal ganglion cells (RGCs) leads to blindness. In the B6;C3-Opa1Q285STOP (het) mouse, an Opa1 mutation causes a decrease in ATP production and a progressive loss in visual acuity, which coincides with pruning of the predominantly ON-centre RGC dendrites. As 670 nm light can increase ATP production and provide neuroprotective effects, we hypothesise that protection from dendritic pruning will be observed in the ON-centre RGCs of the het mouse with 670 nm light. By Sholl analysis, and other measures of dendritic complexity, we found that ex vivo delivery of 670 nm light to retinal explants provides partial protection against the ex vivo retinal ganglion cell dendropathy, triggered by axotomy, in young wild-type mice. By the same methods of analyses, in vivo delivery of 670 nm light to aged wild-type and het mice partial provided protection against ex vivo RGC dendropathy in RGCs from wild-type mice and partial protection in RGCs from het mice. By immunohistochemistry, the transcription factor NFκB was found to be activated in RGCs from aged het mice treated with in vivo 670 nm light. The oxidative stress sensor, DJ1, was upregulated in RGCs from aged wild-type and het mice, by in vivo 670 nm light. The activation of the serine/threonine protein kinase, AKT, which plays a pivotal role in controlling cell survival and apoptosis, was decreased following in vivo 670 nm light treatment in aged wild-type RGCs.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:738357 |
| Date | January 2017 |
| Creators | Beirne, Kathy |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/109384/ |
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