Friday, November 5, 2021

Injectable Treatment Targeting Schlemm's Canal Explored for Congenital Glaucoma

Article: A new treatment for glaucoma?
Source: Northwestern University Medicine
Published: October 18, 2021
Article: New Therapeutic Targets for Glaucoma Identified in Mice
Source: Genetic Engineering & Biotechnology News
Published: October 19, 2021 

ANGPT1 mimetic treatment increased SC area and lowered IOP in mice
Primary congenital glaucoma (PCG) is a pediatric form of glaucoma that results from developmental defects in the trabecular meshwork (TM) and Schlemm's canal (SC). As with other types of glaucoma, this in turn compromises aqueous outflow, causing a build-up of intraocular pressure (IOP) that ultimately damages the optic nerve and leads to vision loss. Although rare, primary congenital glaucoma is devastating in its severity and early onset, with few viable treatment options other than surgery. Some scientists are working on a new class of injectable treatments. In this case, they genetically engineered mouse models that resembled forms of PCG. The authors write, “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 [genome-wide association 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.” Next, they administered intraocular injection of a protein called Hepta-ANGPT1, a recombinant ANGPT1-mimetic, to replace the function of the mutated genes. They report that Hepta-ANGPT1 promoted developmental SC expansion in healthy and Angpt1  deficient eyes, and blunted IOP elevation and RGC loss in one mouse model of primary congenital glaucoma. When injected into the eyes of healthy adult mice, Hepta-ANGPT1 lowered intraocular pressure. They additionally performed single-cell transcriptomic analysis of normal and glaucomatous Angpt1  deficient eyes to investigate TM-SC signaling pathways. The authors highlight the role of ANGPT1-TEK signaling and TM-SC crosstalk in IOP homeostasis that could guide a potential new class of drug therapy for glaucoma that targets Schlemm's canal.

My rating of this study:

Thomson BR, Liu P, Onay T, et al. "Cellular crosstalk regulates the aqueous humor outflow pathway and provides new targets for glaucoma therapies." Nature Communications.  12:6072. 18 October 2021. https://doi.org/10.1038/s41467-021-26346-0 

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