A single gene connects stiffness in glaucoma and the vascular system

Arterial calcification results in arterial stiffness and higher systolic blood pressure. Arterial calcification is prevented by the high expression of the Matrix-Gla gene (MGP) in the vascular smooth muscle cells (VSMC) of the arteries' tunica media. Originally, MGP, a gene highly expressed in cartilage and VSMC, was found to be one of the top expressed genes in the trabecular meshwork. The creation of an Mgp-lacZ Knock-In mouse and the use of mouse genetics revealed that in the eye, Mgp's abundant expression is localized and restricted to glaucoma-associated tissues from the anterior and posterior segments. In particular, it is specifically expressed in the regions of the trabecular meshwork and of the peripapillary sclera that surrounds the optic nerve. Because stiffness in these tissues would significantly alter outflow facility and biomechanical scleral stress in the optic nerve head (ONH), we propose MGP as a strong candidate for the regulation of stiffness in glaucoma. MGP further illustrates the presence of a common function affecting key glaucomatous parameters in the front and back of the eye, and thus offers the possibility for a sole therapeutic target for the disease.