CRISPR-Cas9–based treatment of myocilin-associated glaucoma
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Author(s)
Jain, Ankur
Zode, Gulab
Kasetti, Ramesh B.
Sharma, Tasneem P.
Bugge, Kevin
Searby, Charles C.
Fingert, John H.
Clark, Abbot F.
Sheffield, Val C.
Ran, Fei
Date Issued
October 2017
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Jain, Ankur et al. “CRISPR-Cas9–based Treatment of Myocilin-Associated Glaucoma.” Proceedings of the National Academy of Sciences 114, 42 (October 2017): 11199–11204 © 2017 National Academy of Sciences
Version
Final published version
Abstract
Primary open-angle glaucoma (POAG) is a leading cause of irreversible vision loss worldwide, with elevated intraocular pressure (IOP) a major risk factor. Myocilin (MYOC) dominant gain-of-function mutations have been reported in ∼4% of POAG cases. MYOC mutations result in protein misfolding, leading to endoplasmic reticulum (ER) stress in the trabecular meshwork (TM), the tissue that regulates IOP. We use CRISPR-Cas9–med iated genome editing in cultured human TM cells and in a MYOC mouse model of POAG to knock down expression of mutant MYOC, resulting in relief of ER stress. In vivo genome editing results in lower IOP and prevents further glaucomatous damage. Importantly, using an ex vivo human organ culture system, we demonstrate the feasibility of human genome editing in the eye for this important disease. Keywords: myocilin; CRISPR; glaucoma; trabecular meshwork; genome editing
MIT Department
Institute for Medical Engineering and Science
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
McGovern Institute for Brain Research at MIT
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/PNAS.1706193114
