Retinal neuronal remodelling in a model of optic atrophy

Doctoral thesis English OPEN
Williams, Peter
  • Subject: RE
    mesheuropmc: eye diseases | sense organs

The heterozygous mutation, B6;C3-Opa1Q285STOP, leads to a 50% reduction in Opa1 transcript and protein in the mouse retina and neural tissues and models autosomal dominant optic atrophy and presents with visual dysfunction and structural changes in the retina and optic nerve. This thesis explores the intimate relationship between retinal ganglion cell dendritic architecture, health and synaptic connectivity as influenced by the mitochondrial fusion protein Opa1. \ud Using a range experimental paradigms it is reported here retinal ganglion cell dendritic atrophy which is exacerbated with age and localised exclusively to sublamina b of the inner plexiform layer. There is a marked reduction in the number of glutamatergic synaptic sites and PSD95 levels on ON-centre retinal ganglion cells. In addition, there is a significant increase in synaptic vesicle number and density in both ON and OFF bipolar cells.\ud These processes cast light on the intimate relationship between normal mitochondrial fusion and fission balances, as influenced by the OPA1 protein, in neural cell connectivity in the mammalian retina and the changes shown here serve as an exciting biomarker for disease and rescue and recovery therapeutics.
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