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Opa1 is essential for retinal ganglion cell synaptic architecture and connectivity

Williams, Pete A., Piechota, Malgorzata, Von Ruhland, Christopher John, Taylor, Elaine, Morgan, James Edwards ORCID: and Votruba, Marcela ORCID: 2012. Opa1 is essential for retinal ganglion cell synaptic architecture and connectivity. Brain 135 (2) , pp. 493-505. 10.1093/brain/awr330

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Retinal ganglion cell dendritic pruning has been reported in association with a 50% reduction in Opa1 transcript and protein in retinal and neural tissue, which manifests as visual dysfunction in the heterozygous mutant mouse, B6;C3-Opa1Q285STOP. Here we report a marked reduction in retinal ganglion cell synaptic connectivity in the absence of soma loss and explore the mechanism and relationship between mitochondrial integrity and synaptic connectivity. We observed decreased levels of postsynaptic density protein 95 in Opa1+/− mutant mice consistent with synaptic loss in the inner plexiform layer. Glutamatergic but not γ-aminobutyric acid-ergic synaptic sites were reduced in Opa1+/− mice. We observed increased synaptic vesicle number in bipolar cell terminal arbours assessed by immunohistochemistry, electron microscopy and western blot analysis. These changes occur without significant loss of mitochondrial membrane potential in retina and optic nerve. Analysis of biolistically transfected retinal ganglion cells shows the retraction of mitochondria towards the soma, and mitochondrial fragmentation, preceding dendritic loss. 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Optometry and Vision Sciences
Systems Immunity Research Institute (SIURI)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: R Medicine > RE Ophthalmology
Publisher: Oxford University Press
ISSN: 0006-8950
Last Modified: 05 Nov 2022 15:08

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