| First Author | Kim HT | Year | 2015 |
| Journal | Cell Rep | Volume | 13 |
| Issue | 5 | Pages | 990-1002 |
| PubMed ID | 26565912 | Mgi Jnum | J:228952 |
| Mgi Id | MGI:5749891 | Doi | 10.1016/j.celrep.2015.09.075 |
| Citation | Kim HT, et al. (2015) Mitochondrial Protection by Exogenous Otx2 in Mouse Retinal Neurons. Cell Rep 13(5):990-1002 |
| abstractText | 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. |
