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dc.contributor.authorQu, Juan
dc.contributor.authorMatsouaka, Roland Albert
dc.contributor.authorBetensky, Rebecca Aubrey
dc.contributor.authorHyman, Bradley Theodore
dc.contributor.authorGrosskreutz, Cynthia Lee
dc.date.accessioned2013-04-24T18:59:46Z
dc.date.issued2012
dc.identifier.citationQu, Juan, Roland Albert Matsouaka, Rebecca Aubrey Betensky, Bradley Theodore Hyman, and Cynthia Lee Grosskreutz. 2012. Calcineurin activation causes retinal ganglion cell degeneration. Molecular Vision 18:2828-2838.en_US
dc.identifier.issn1090-0535en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10581402
dc.description.abstractPurpose: We previously reported that calcineurin, a Ca2+/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.en_US
dc.language.isoen_USen_US
dc.publisherMolecular Visionen_US
dc.relation.isversionofhttp://www.molvis.org/molvis/v18/a289en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519372/pdf/en_US
dash.licenseLAA
dc.titleCalcineurin activation causes retinal ganglion cell degenerationen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalMolecular Visionen_US
dash.depositing.authorBetensky, Rebecca Aubrey
dc.date.available2013-04-24T18:59:46Z
dash.contributor.affiliatedMatsouaka, Roland Albert
dash.contributor.affiliatedQu, Juan
dash.contributor.affiliatedBetensky, Rebecca
dash.contributor.affiliatedGrosskreutz, Cynthia
dash.contributor.affiliatedHyman, Bradley


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