eLife | |
AAV-Txnip prolongs cone survival and vision in mouse models of retinitis pigmentosa | |
Helian Feng1  Parimal Rana2  Yunlu Xue3  Constance L Cepko4  Sean K Wang4  David M Wu5  Emma R West6  Christin M Hong6  | |
[1] Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, United States;Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, United States;Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, United States;Department of Ophthalmology, Harvard Medical School, Boston, United States;Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, United States;Department of Ophthalmology, Harvard Medical School, Boston, United States;Howard Hughs Medical Institute, Chevy Chase, United States;Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, United States;Department of Ophthalmology, Harvard Medical School, Boston, United States;Retina Service, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, United States;Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, United States;Howard Hughs Medical Institute, Chevy Chase, United States; | |
关键词: retina; neurodegeneration; gene therapy; cone photoreceptor; retinal metabolism; mitochondria; Mouse; | |
DOI : 10.7554/eLife.66240 | |
来源: eLife Sciences Publications, Ltd | |
【 摘 要 】
Retinitis pigmentosa (RP) is an inherited retinal disease affecting >20 million people worldwide. Loss of daylight vision typically occurs due to the dysfunction/loss of cone photoreceptors, the cell type that initiates our color and high-acuity vision. Currently, there is no effective treatment for RP, other than gene therapy for a limited number of specific disease genes. To develop a disease gene-agnostic therapy, we screened 20 genes for their ability to prolong cone photoreceptor survival in vivo. Here, we report an adeno-associated virus vector expressing Txnip, which prolongs the survival of cone photoreceptors and improves visual acuity in RP mouse models. A Txnip allele, C247S, which blocks the association of Txnip with thioredoxin, provides an even greater benefit. Additionally, the rescue effect of Txnip depends on lactate dehydrogenase b (Ldhb) and correlates with the presence of healthier mitochondria, suggesting that Txnip saves RP cones by enhancing their lactate catabolism.
【 授权许可】
CC BY
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
RO202106210544445ZK.pdf | 10072KB | download |