Mitochondrial Protection by Exogenous Otx2 in Mouse Retinal Neurons

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OTX2 (orthodenticle homeobox 2) haplodeficiency causes diverse defects in mammalian visual systems ranging from retinal dysfunction to anophthalmia. We find that the retinal dystrophy of Otx2(+/GFP) heterozygous knockin mice is mainly due to the loss of bipolar cells and consequent deficits in retinal activity. Among bipolar cell types, OFF-cone bipolar subsets, which lack autonomous Otx2 gene expression but receive Otx2 proteins from photoreceptors, degenerate most rapidly in Otx2(+/GFP) mouse retinas, suggesting a neuroprotective effect of the imported Otx2 protein. In support of this hypothesis, retinal dystrophy in Otx2(+/GFP) mice is prevented by intraocular injection of Otx2 protein, which localizes to the mitochondria of bipolar cells and facilitates ATP synthesis as a part of mitochondrial ATP synthase complex. Taken together, our findings demonstrate a mitochondrial function for Otx2 and suggest a potential therapeutic application of OTX2 protein delivery in human retinal dystrophy.
Publisher
CELL PRESS
Issue Date
2015-11
Language
English
Article Type
Article
Keywords

PHOTORECEPTOR CELL FATE; VISUAL-CORTEX; BIPOLAR CELLS; GENE; DIFFERENTIATION; SPECIFICATION; HOMEOPROTEIN; PLASTICITY; PHENOTYPES; MUTATIONS

Citation

CELL REPORTS, v.13, no.5, pp.990 - 1002

ISSN
2211-1247
DOI
10.1016/j.celrep.2015.09.075
URI
http://hdl.handle.net/10203/205182
Appears in Collection
BS-Journal Papers(저널논문)
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