高血糖が血管内皮細胞および肝細胞に及ぼす影響に関する基礎研究

Abstract

Chronically elevated intraocular pressure (IOP) is the major risk factorof primary open-angle glaucoma, a leading cause of lindness. Dysfunctionof the trabecular meshwork (TM), which controls the outflow of aqueoushumor (AqH) from the anterior chamber, is the major cause of elevated IOP.Here, we demonstrate that mice ficient in the Krüppel-like zinc fingertranscriptional factor GLI-similar-1 (GLIS1) develop chronically elevatedIOP. Magnetic resonance aging and histopathological analysis reveal thatdeficiency in GLIS1 expression induces progressive degeneration of the TM,eading to inefficient AqH drainage from the anterior chamber and elevatedIOP. Transcriptome and cistrome analyses identified several glaucoma- andextracellular matrix-associated genes as direct transcriptional targets ofGLIS1. We also identified a significant association between GLIS1 variantrs941125 and glaucoma in humans (P = 4.73 × 10−6), further supporting arole for GLIS1 into laucoma etiology. Our study identifies GLIS1 as acritical legulator of TM function and maintenance, AqH dynamics, and IOP.