Mitochondrial Protection by Exogenous Otx2 in Mouse Retinal Neurons

作者：Kim Hyoung Tai; Kim Soung Jung; Sohn Young In; Paik Sun Sook; Caplette Romain; Simonutti Manuel; Moon Kyeong Hwan; Lee Eun Jung; Min Kwang Wook; Kim Mi Jeong; Lee Dong Gi; Simeone Antonio; Lamonerie Thomas; Furukawa Takahisa; Choi Jong Soon; Kweon Hee Seok; Picaud Serge; Kim In Beom; Shong Minho; Kim Jin Woo^*

来源：Cell Reports, 2015, 13(5): 990-1002.

DOI：10.1016/j.celrep.2015.09.075

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.

• 出版日期2015-11-3