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Calcineurin activation causes retinal ganglion cell degeneration.

dc.contributor.author Qu, J
dc.contributor.author Matsouaka, Roland Albert
dc.contributor.author Betensky, RA
dc.contributor.author Hyman, BT
dc.contributor.author Grosskreutz, CL
dc.coverage.spatial United States
dc.date.accessioned 2017-11-01T16:32:28Z
dc.date.available 2017-11-01T16:32:28Z
dc.date.issued 2012
dc.identifier https://www.ncbi.nlm.nih.gov/pubmed/23233785
dc.identifier.uri https://hdl.handle.net/10161/15726
dc.description.abstract PURPOSE: We previously reported that calcineurin, a Ca(2+)/calmodulin-dependent serine/threonine phosphatase, is activated and proposed that it participates in retinal ganglion cell (RGC) apoptosis in two rodent ocular hypertension models. In this study, we tested whether calcineurin activation by itself, even in the absence of ocular hypertension, is sufficient to cause RGC degeneration. METHODS: We compared RGC and optic nerve morphology after adeno-associated virus serotype 2 (AAV2)-mediated transduction of RGCs with constitutively active calcineurin (CaNCA) or unactivated, wild-type calcineurin (CaNwt). Retinas and optic nerves were harvested 7-16 weeks after injection of the AAV into mouse vitreous. In flatmounted retinas, the transduced RGCs were identified with immunohistochemistry. The morphology of the RGCs was revealed by immunostaining for neurofilament SMI32 or by using GFP-M transgenic mice. A modified Sholl analysis was applied to analyze the RGC dendritic morphology. Optic nerve damage was assessed with optic nerve grading according to the Morrison standard. RESULTS: CaNwt and CaNCA were highly expressed in the injected eyes. Compared to the CaNwt-expressing RGCs, the CaNCA-expressing RGCs had smaller somas, smaller dendritic field areas, shorter total dendrite lengths, and simpler dendritic branching patterns. At 16 weeks, the CaNCA-expressing eyes had greater optic nerve damage than the CaNwt-expressing eyes. CONCLUSIONS: Calcineurin activation is sufficient to cause RGC dendritic degeneration and optic nerve damage. These data support the hypothesis that calcineurin activation is an important mediator of RGC degeneration, and are consistent with the hypothesis that calcineurin activation may contribute to RGC neurodegeneration in glaucoma.
dc.language eng
dc.relation.ispartof Mol Vis
dc.subject Animals
dc.subject Axons
dc.subject Calcineurin
dc.subject Dendrites
dc.subject Dependovirus
dc.subject Enzyme Activation
dc.subject Genetic Vectors
dc.subject Green Fluorescent Proteins
dc.subject Immunohistochemistry
dc.subject Intravitreal Injections
dc.subject Mice
dc.subject Mice, Transgenic
dc.subject Nerve Degeneration
dc.subject Optic Nerve
dc.subject Retinal Degeneration
dc.subject Retinal Ganglion Cells
dc.subject Transduction, Genetic
dc.subject Transgenes
dc.title Calcineurin activation causes retinal ganglion cell degeneration.
dc.type Journal article
pubs.author-url https://www.ncbi.nlm.nih.gov/pubmed/23233785
pubs.begin-page 2828
pubs.end-page 2838
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biostatistics & Bioinformatics
pubs.organisational-group Duke
pubs.organisational-group Duke Clinical Research Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group School of Medicine
pubs.publication-status Published
pubs.volume 18
dc.identifier.eissn 1090-0535


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