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.
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Authors | Hyoung-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 |
Journal | Cell reports
(Cell Rep)
Vol. 13
Issue 5
Pg. 990-1002
(Nov 03 2015)
ISSN: 2211-1247 [Electronic] United States |
PMID | 26565912
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Otx Transcription Factors
- Otx2 protein, mouse
- Adenosine Triphosphate
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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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