BMB Rep. 2016; 49(2): 69-70  
Donating Otx2 to support neighboring neuron survival
Hyoung-Tai Kim1, Alain Prochiantz2 & Jin Woo Kim1,*
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea, 2Center for Interdisciplinary Research in Biology (CIRB), College de France, Paris, France
Correspondence to: E-mail:
Received: January 11, 2016; Published online: February 28, 2016.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

Mutations of orthodentricle homeobox 2 (OTX2) in human and mice often cause retinal dystrophy and nyctalopia, suggesting a role of OTX2 in mature retina, in addition to its functions in the development of the eye and retina. In support of this, the number of bipolar cells in Otx2+/? post-natal mouse retina was found to be significantly lower than normal. Degeneration of the cells becomes greater as the mice age, leading to the loss of vision. Especially, the type-2 OFF-cone bipolar cells, which do not express Otx2 mRNA but carry Otx2 protein, are most sensitive to Otx2 haplodeficiency. Interestingly, this bipolar cell subpopulation imports Otx2 protein from photoreceptors to protect itself from glutamate excitotoxicity in the dark. Moreover, in the bipolar cells, the exogenous Otx2 relocates to the mitochondria to support mitochondrial ATP synthesis. This novel mitochondrial activity of exogenous Otx2 highlights the therapeutic potential of Otx2 protein transduction in retinal dystrophy.
Keywords: Glutamate excitotoxicity, Intercellular protein transfer, Mitochondria, Otx2, Retina

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