TY - JOUR T1 - GLIS1 regulates trabecular meshwork function and intraocular pressure and is associated with glaucoma in humans JF - bioRxiv DO - 10.1101/2021.07.02.450719 SP - 2021.07.02.450719 AU - K. Saidas Nair AU - Chitrangda Srivastava AU - Robert V. Brown AU - Swanand Koli AU - Hélène Choquet AU - Hong Soon Kang AU - Yien-Ming Kuo AU - Sara A. Grimm AU - Caleb Sutherland AU - Alexandra Badea AU - G. Allan Johnson AU - Yin Zhao AU - Jie Yin AU - Kyoko Okamoto AU - Graham Clark AU - Teresa Borras AU - Gulab Zode AU - Krishnakumar Kizhatil AU - Subhabrata Chakrabarti AU - Simon W.M. John AU - Eric Jorgenson AU - Anton M. Jetten Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/07/05/2021.07.02.450719.abstract N2 - Chronically elevated intraocular pressure (IOP) is the major risk factor of primary open- angle glaucoma, a leading cause of blindness. Dysfunction of the trabecular meshwork (TM), which controls the outflow of aqueous humor (AqH) from the anterior chamber, is the major cause of elevated IOP. Here, we demonstrate that mice deficient in the Krüppel- like zinc finger transcriptional factor GLI-similar-1 (GLIS1) develop chronically elevated IOP. Magnetic resonance imaging and histopathological analysis reveal that deficiency in GLIS1 expression induces progressive degeneration of the TM, leading to inefficient AqH drainage from the anterior chamber and elevated IOP. Transcriptome and cistrome analyses identified several glaucoma- and extracellular matrix-associated genes as direct transcriptional targets of GLIS1. We also identified a significant association between GLIS1 variant rs941125 and glaucoma in humans (P=4.73x10-6), further supporting a role for GLIS1 into glaucoma etiology. Our study identifies GLIS1 as a critical regulator of TM function and maintenance, AqH dynamics, and IOP.Competing Interest StatementThe authors have declared no competing interest. ER -