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Mitochondrial Protection by Exogenous Otx2 in Mouse Retinal Neurons.

Abstract
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.
AuthorsHyoung-Tai Kim, Soung Jung Kim, Young-In Sohn, Sun-Sook Paik, Romain Caplette, Manuel Simonutti, Kyeong Hwan Moon, Eun Jung Lee, Kwang Wook Min, Mi Jeong Kim, Dong-Gi Lee, Antonio Simeone, Thomas Lamonerie, Takahisa Furukawa, Jong-Soon Choi, Hee-Seok Kweon, Serge Picaud, In-Beom Kim, Minho Shong, Jin Woo Kim
JournalCell reports (Cell Rep) Vol. 13 Issue 5 Pg. 990-1002 (Nov 03 2015) ISSN: 2211-1247 [Electronic] United States
PMID26565912 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Chemical References
  • Otx Transcription Factors
  • Otx2 protein, mouse
  • Adenosine Triphosphate
Topics
  • Adenosine Triphosphate (metabolism)
  • Animals
  • Intravitreal Injections
  • Mice
  • Mitochondria (drug effects, metabolism)
  • Otx Transcription Factors (administration & dosage, pharmacology, therapeutic use)
  • Retinal Bipolar Cells (drug effects, metabolism)
  • Retinal Dystrophies (drug therapy)

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