JMG, Animals, Aqueous Humor, Chromatin Immunoprecipitation Sequencing, DNA-Binding Proteins, Disease Models, Animal, Gene Expression Profiling, Gene Expression Regulation, Glaucoma, HEK293 Cells, Humans, Intraocular Pressure, Mice, Inbred C57BL, Mice, Knockout, RNA-Seq, Trabecular Meshwork, Transcription Factors
Nat Commun 2021 Aug 12; 12(1):4877
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 = 4.73 × 10
Nair, K Saidas; Srivastava, Chitrangda; Brown, Robert V; Koli, Swanand; Choquet, Hélène; Kang, Hong Soon; Kuo, Yien-Ming; Grimm, Sara A; Sutherland, Caleb; Badea, Alexandra; Johnson, G Allan; Zhao, Yin; Yin, Jie; Okamoto, Kyoko; Clark, Graham; Borrás, Terete; Zode, Gulab; Kizhatil, Krishnakumar; Chakrabarti, Subhabrata; John, Simon W M; Jorgenson, Eric; and Jetten, Anton M, "GLIS1 regulates trabecular meshwork function and intraocular pressure and is associated with glaucoma in humans." (2021). Faculty Research 2021. 173.