October 10, 2022

Opening a window to glaucoma

A metalloprotease enzyme plays an important role in retinal ganglion cell development, Vanderbilt researchers discovered; studying it and other family members may lead to the identification of novel targets for treating glaucoma.

Glaucoma, caused by neurodegeneration of retinal ganglion cells, is the leading cause of irreversible vision loss affecting tens of millions of people worldwide. 

Previous research at VUMC has shown that mutations in the gene for Adamts10, a metalloprotease enzyme, cause glaucoma in dogs. Adamts10 regulates signaling through transforming growth factor beta (TGF-beta), which promotes the development of retinal ganglion cells. 

In a recent study, John Kuchtey, PhD, and colleagues found that reducing Adamts10 expression in zebrafish embryos drastically reduced TGF-beta signaling in the eye and prevented formation of an ordered retinal ganglion cell layer. Directly inhibiting the TGF-beta receptor had a similar effect. 

Their findings, reported in September in the journal Frontiers in Molecular Biosciences, revealed for the first time that Adamts10 plays an important role in retinal ganglion cell development mediated by TGF-beta signaling. 

Determining the biological functions of Adamts genes may lead to the identification of novel targets for the treatment of glaucoma, the researchers concluded.

Lauren Wareham, PhD, Amy Whitener, PhD, and Hang-Jing Wu, PhD shared first authorship. Co-authors were Shu-Yu Wu, PhD, Hassane Mchaourab, PhD, Douglas Mortlock, PhD, and Rachel Kuchtey, MD, PhD.

This work was supported by the Vanderbilt Eye Institute, National Institutes of Health grants EY027746, EY012018, EY007135, and EY008126, and by Research to Prevent Blindness, Inc.