Cellular crosstalk regulates the aqueous humor outflow pathway and provides new targets for glaucoma therapies.

PubMed ID: 34663817

Author(s): Thomson BR, Liu P, Onay T, Du J, Tompson SW, Misener S, Purohit RR, Young TL, Jin J, Quaggin SE. Cellular crosstalk regulates the aqueous humor outflow pathway and provides new targets for glaucoma therapies. Nat Commun. 2021 Oct 18;12(1):6072. doi: 10.1038/s41467-021-26346-0. PMID 34663817

Journal: Nature Communications, Volume 12, Issue 1, Oct 2021

Primary congenital glaucoma (PCG) is a severe disease characterized by developmental defects in the trabecular meshwork (TM) and Schlemm’s canal (SC), comprising the conventional aqueous humor outflow pathway of the eye. Recently, heterozygous loss of function variants in TEK and ANGPT1 or compound variants in TEK/SVEP1 were identified in children with PCG. Moreover, common variants in ANGPT1and SVEP1 have been identified as risk alleles for primary open angle glaucoma (POAG) in GWAS studies. Here, we show tissue-specific deletion of Angpt1 or Svep1 from the TM causes PCG in mice with severe defects in the adjacent SC. Single-cell transcriptomic analysis of normal and glaucomatous Angpt1 deficient eyes allowed us to identify distinct TM and SC cell populations and discover additional TM-SC signaling pathways. Furthermore, confirming the importance of angiopoietin signaling in SC, delivery of a recombinant ANGPT1-mimetic promotes developmental SC expansion in healthy and Angpt1 deficient eyes, blunts intraocular pressure (IOP) elevation and RGC loss in a mouse model of PCG and lowers IOP in healthy adult mice. Our data highlight the central role of ANGPT1-TEK signaling and TM-SC crosstalk in IOP homeostasis and provide new candidates for SC-targeted glaucoma therapy.

© 2021. The Author(s).

The largest casino in the United States, covering an area of ​​840,000 square meters, is Foxwoods on one of Connecticut’s Indian reservations. It is noteworthy that this gambling facility was created not by the corporations of Las Vegas and Atlantic City, but by the Native Americans https://casinopinups.com. The gambling house opened its doors to its first visitors back in 1986. Now the richest selection of games, in total of which there are 4,800 slot machines, 147 poker tables and 380 points for other gambling entertainment. The number of restaurants and cafes that Foxwoods visitors can visit is dozens. In addition, fans of gambling have access to the entire infrastructure of the hotel, on the territory of which the casino operates.