Vasorin, an antagonist of TGF-β is decreased in glaucoma patients

Abstract

Purpose : To explore the role of vasorin, a common constituent of human aqueous humor, and a known regulator of TGF-β activity in the etiology of glaucoma and trabecular meshwork physiology.

Methods : Vasorin levels in the aqueous humor of glaucoma patients (POAG and Uveitis) were determined by mass spectrometry and ELISA. The effects of vasorin on TGF-β2 induced activation of SMAD signaling, and the effects of ADAM17 on vasorin secretion in human TM, were evaluated by immunoblot analyses.

Results : Aqueous humor derived from both primary open-angle glaucoma (POAG, n=20)) and uveitis glaucoma (n=12) patients showed a significant but moderate decrease in vasorin levels compared to age and gender matched non-glaucoma (cataract) patients. Recombinant vasorin significantly suppressed TGF-β2-induced SMAD 2/3 phosphorylation and α-smooth muscle actin, in human TM cells compared to control TM cells. The profile of extracellular vasorin of human TM cells was found to be different with treatment of ADAM17 inhibitor. Although vasorin has been reported to be anti-apoptotic and localized to the mitochondria in mouse embryonic fibroblasts, the protein exhibited vesicular distribution in human TM cells.

Conclusions : These results reveal that levels of the active form of vasorin (secreted extracellular domain of the transmembrane form of vasorin) are decreased in the aqueous humor of POAG and uveitis glaucoma patients. Vasorin is known to antagonize TGF-β2 signaling in human TM cells. Taken together, these findings suggest a crucial role for vasorin in the etiology of glaucoma, and support the potential therapeutic significance of vasorin in treatment of glaucoma.

This is a 2021 ARVO Annual Meeting abstract.