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Abstract #74512 Published in IGR 19-1
CRISPR-Cas9-based treatment of myocilin-associated glaucoma
Jain A; Zode G; Kasetti RB; Ran FA; Yan W; Sharma TP; Bugge K; Searby CC; Fingert JH; Zhang F; Clark AF; Sheffield VCProceedings of the National Academy of Sciences of the United States of America 2017; 114: 11199-11204
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.
Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242.
Full articleClassification:
11.9 Gene therapy (Part of: 11 Medical treatment)
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
