CRISPR-Cas9–based treatment of myocilin-associated glaucoma

Ankur Jain, Gulab Zode, Ramesh B. Kasetti, Fei A. Ran, Winston Yan, Tasneem P. Sharma, Kevin Bugge, Charles C. Searby, John H. Fingert, Feng Zhang, Abbot F. Clark, Val C. Sheffield

Research output: Contribution to journalArticlepeer-review

104 Scopus citations


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–mediated 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.

Original languageEnglish
Pages (from-to)11199-11204
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number42
StatePublished - 17 Oct 2017


  • Genome editing
  • Glaucoma
  • Myocilin
  • Trabecular meshwork


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