Calcineurin activation causes retinal ganglion cell degeneration

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Calcineurin activation causes retinal ganglion cell degeneration

Show simple item record Qu, Juan Matsouaka, Roland Albert Betensky, Rebecca Aubrey Hyman, Bradley Theodore Grosskreutz, Cynthia Lee 2013-04-24T18:59:46Z 2012
dc.identifier.citation Qu, 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.issn 1090-0535 en_US
dc.description.abstract Purpose: 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.iso en_US en_US
dc.publisher Molecular Vision en_US
dc.relation.isversionof en_US
dc.relation.hasversion en_US
dash.license LAA
dc.title Calcineurin activation causes retinal ganglion cell degeneration en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal Molecular Vision en_US Betensky, Rebecca Aubrey 2013-04-24T18:59:46Z

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