Journal article
Tau inclusions in retinal ganglion cells of human P301S tau transgenic mice: Effects on axonal viability
L Gasparini, R Anthony Crowther, KR Martin, N Berg, M Coleman, M Goedert, MG Spillantini
Neurobiology of Aging | ELSEVIER SCIENCE INC | Published : 2011
Abstract
Tau inclusions play a key role in the pathogenesis of tauopathies. Altered tau levels have been detected in retina and optic nerve of patients with glaucoma, suggesting the possibility of shared pathogenic mechanisms with tauopathies. Here we report that hyperphosphorylated transgenic tau accumulates in the nerve fibre layer and, from 2 months of age, aggregates into filamentous inclusions in retinal ganglion cells of human P301S tau transgenic mice. Axonopathy and accumulation of hyperphosphorylated tau in the nerve fibre layer preceded inclusion formation. Hyperphosphorylated tau and tau inclusions were also detected in cultured retinal explants from 5-month-old transgenic mice. Axonal out..
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Awarded by Medical Research Council
Funding Acknowledgements
We thank Drs. Ron Meyer, Jill Miotke (Univ. of California, Irvine, CA), Natalie Bull and Nephtali Marina Gonzalez (Univ. of Cambridge, UK) for technical advice. We are grateful to Helen Gossage, Elena Fineberg and Mike Peacock for technical assistance. We thank Drs. Peter Davies (Albert Einstein College of Medicine, New York, NY) for the gift of the PHF-1 antibody, Bill Blakemore (Univ. of Cambridge, UK) for helpful discussions and Jeremy Skepper (Univ. of Cambridge, UK) for assistance with electron microscopy. LG is the recipient of an Alzheimer's Research Trust Fellowship (ART/RF2005/05). This work was supported by the UK Alzheimer's Research Trust and the Medical Research Council.