@article{e51bbc61766141648714ee418c76a18c,
title = "CNTF Gene Therapy Confers Lifelong Neuroprotection in a Mouse Model of Human Retinitis Pigmentosa",
abstract = "The long-term outcome of neuroprotection as a therapeutic strategy for preventing cell death in neurodegenerative disorders remains unknown, primarily due to slow disease progression and the inherent difficulty of assessing neuronal survival in vivo. Employing a murine model of retinal disease, we demonstrate that ciliary neurotrophic factor (CNTF) confers life-long protection against photoreceptor degeneration. Repetitive retinal imaging allowed the survival of intrinsically fluorescent cone photoreceptors to be quantified in vivo. Imaging of the visual cortex and assessment of visually-evoked behavioral responses demonstrated that surviving cones retain function and signal correctly to the brain. The mechanisms underlying CNTF-mediated neuroprotection were explored through transcriptome analysis, revealing widespread upregulation of proteolysis inhibitors, which may prevent cellular/extracellular matrix degradation and complement activation in neurodegenerative diseases. These findings provide insights into potential novel therapeutic avenues for diseases such as retinitis pigmentosa and amyotrophic lateral sclerosis, for which CNTF has been evaluated unsuccessfully in clinical trials.",
author = "Lipinski, {Daniel M.} and Barnard, {Alun R.} and Singh, {Mandeep S.} and Chris Martin and Lee, {Edward J.} and Davies, {Wayne I.L.} and MacLaren, {Robert E.}",
note = "Funding Information: This research was funded by Fight for Sight , the Wellcome Trust , the Health Foundation , the Medical Research Council , the Royal College of Surgeons of Edinburgh , the Oxford Stem Cell Institute and the NIHR Ophthalmology and Oxford Biomedical Research Centre (all bodies UK based). W.I.L.D. was funded by an Australian Research Council (ARC) Future Fellowship ( FT110100176 ) and an ARC Discovery Project grant ( DP140102117 ). C.M. was supported by a Royal Society University Research Fellowship. D.M.L. was sponsored in part by a Fulbright-Fight for Sight Research Scholarship. We thank the High-Throughput Genomics Group at the Wellcome Trust Centre for Human Genetics (funded by Wellcome Trust grant reference 090532/Z/09/Z and MRC Hub grant G0900747 91070 ; University of Oxford ) for the generation of the sequencing data. The authors would also like to thank Oleksandr Moskalenko (High Performance Computing Centre, University of Florida, USA) for assistance in the analysis of RNA-Seq data. D.M.L. would like to thank Bally (currently, University of Florida, USA) for helpful contributions throughout the preparation of this manuscript. The authors declare that they have no relevant conflicts of interest. Publisher Copyright: {\textcopyright} The American Society of Gene & Cell Therapy.",
year = "2015",
month = aug,
day = "1",
doi = "10.1038/mt.2015.68",
language = "English (US)",
volume = "23",
pages = "1308--1319",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "8",
}