Project: SUF
ITGA9 as a Novel Target to Activate Angiopoietin/TIE Signaling in Schlemm’s Canal
This funded project investigates the role of Integrin Alpha-9 (ITGA9) as a novel regulator of angiopoietin/TIE signaling in Schlemm’s canal and explores its therapeutic potential for lowering intraocular pressure (IOP) in glaucoma. Schlemm’s canal is a specialized vascular structure essential for aqueous humour drainage and IOP regulation, and its dysfunction is a major contributor to glaucoma development. Importantly, the formation and maintenance of Schlemm’s canal relies on signaling pathways that are closely related to lymphangiogenesis, including VEGFC/VEGFR3 and ANG/TIE signaling pathways.
Recent unpublished findings identified ITGA9 as a regulator of angiopoietin/TIE signaling in mature lymphatic vessels. The project now aims to determine whether ITGA9 exerts a similar inhibitory function in Schlemm’s canal cells and whether blocking ITGA9 can enhance ANG/TIE signaling to improve Schlemm’s canal function and reduce IOP.
The project combines in vivo and in vitro approaches to investigate the molecular mechanisms underlying ITGA9-mediated regulation of ANG/TIE signaling. Genetically modified mice will be used to assess the impact of ITGA9 signaling on Schlemm’s canal integrity and intraocular pressure. Complementary cellular studies using primary human lymphatic endothelial cells will explore how ITGA9 influences VEGFC- and ANG/TIE-dependent signaling pathways and whether pharmacological inhibition of ITGA9 enhances endothelial signaling responses.
These approaches may not only improve Schlemm’s canal function but could also enhance the efficacy of existing ANG/TIE-targeted glaucoma therapies.
By linking vascular biology, lymphatic signaling, and glaucoma research, this project establishes a highly translational framework for developing innovative therapeutic strategies targeting ocular pressure regulation. The findings are expected to (1) support the notion that ITGA9 acts as a novel modulator of Schlemm’s canal homeostasis and (2) provide a foundation for future combination therapies aimed at preventing glaucoma progression and preserving vision.
Key Methods
- Conditional ITGA9 knockout mouse models
- TIE2 heterozygous glaucoma-associated mouse models
- Primary human dermal lymphatic endothelial cell (HDLEC) cultures
