GLIS1 regulates trabecular meshwork function and intraocular pressure and is associated with glaucoma in humans.

Journal Article (Journal Article)

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 × 10-6), 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.

Full Text

Duke Authors

Cited Authors

  • Nair, KS; Srivastava, C; Brown, RV; Koli, S; Choquet, H; Kang, HS; Kuo, Y-M; Grimm, SA; Sutherland, C; Badea, A; Johnson, GA; Zhao, Y; Yin, J; Okamoto, K; Clark, G; Borrás, T; Zode, G; Kizhatil, K; Chakrabarti, S; John, SWM; Jorgenson, E; Jetten, AM

Published Date

  • August 12, 2021

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • 4877 -

PubMed ID

  • 34385434

Pubmed Central ID

  • PMC8361148

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-021-25181-7

Language

  • eng

Conference Location

  • England