A proof-of-concept study demonstrates therapeutic editing of a mutation underlying a form of glaucoma in a mouse model. Mutations in the myocilin gene (MYOC) can lead to the misfolding and toxic buildup of the encoded protein in the trabecular meshwork (TM), a tissue that regulates pressure inside the eyes, triggering the death of TM cells, raising intraocular pressure, and leading to glaucoma. Val Sheffield and colleagues used CRISPR/Cas9-mediated genome editing to disrupt the production of mutant myocilin in mouse and human TM cells, as well as in a mouse model of primary open angle glaucoma. Cells in which mutant MYOC was disrupted exhibited reduced levels of both myocilin and protein biomarkers of TM cell stress. Intravitreal injection of an adenovirus-based CRISPR construct that disrupted mutant MYOC lowered intraocular pressure and prevented progressive eye damage in the mouse model, compared with mice that received a control injection. The CRISPR construct also reversed elevated intraocular pressure in mice that exhibited elevated pressure for 9 months before treatment onset. Further, the authors demonstrated that treatment of perfusion-cultured human eyes with the CRISPR construct could disrupt secretion of myocilin into the culture medium, suggesting the translational potential of the approach. According to the authors, the findings provide a basis for the development of therapeutic genome editing for a common eye disorder with genetic underpinnings.
Article #17-06193: "CRISPR-Cas9-based treatment of myocilinassociated glaucoma," by Ankur Jain et al.
MEDIA CONTACT: Val Sheffield, University of Iowa, Iowa City, IA; tel: 319-335-6898; e-mail: <val-sheffield@uiowa.edu>
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