All TIEd up: mechanisms of Schlemm’s canal maintenance

A Small Molecule Inhibitor of VE-PTP Activates Tie2 in Schlemm's Canal Increasing Outflow Facility and Reducing Intraocular Pressure

“…Specifically, Tie2 is expressed and activated in SC endothelial cells both during development and after a mature SC lumen has formed in mice. [18][19][20] Disruption of the Tie2 pathway in mice, by conditional knockout of Tie2 or its ligands (Angpt1 and Angpt2) early in postnatal development, results in failure of SC formation, which is associated with increased IOP and optic nerve pathology resembling human congenital glaucoma. [19][20][21] Developmental SC defects in Tie 2 heterozygote mice can be partially rescued by mice expressing only one allele of vascular endothelial protein tyrosine phosphatase (VE-PTP); but interference with VE-PTP expression or function in fully developed mice was not reported.…”

Minimally Invasive Glaucoma Surgery: What Do We Know? Where Should We Go?

“…57,[63][64][65][66][67][68] The complexity of the signaling pathway involved in SC development and in the initiation and maintenance of aqueous humor drainage have been demonstrated in multiple transgenic mice models. [56][57][58][59][60][68][69][70] It has been shown that SCEs are postnatally determined to acquire a lymphatic phenotype through the upregulation of Prox1. Tie2 is expressed before Prox1 in SCEs and is maintained at a high level to critically regulate SC integrity during the adulthood.…”

“…The latter had a lower expression of lymphatic vessel markers and increased expression of blood vessels and mesenchymal features. 60,69 Interestingly, the age-related changes in SC could be rescued by a TIE2-agonistic antibody that can potentially treat POAG. 60,62,[68][69][70] These experimental results might somehow explain the clinical outcome.…”

“…60,69 Interestingly, the age-related changes in SC could be rescued by a TIE2-agonistic antibody that can potentially treat POAG. 60,62,[68][69][70] These experimental results might somehow explain the clinical outcome. Indeed, when we perform canaloplasty on patients with POAG with failed trabeculectomy, the microcatheter could be easily inserted around the entire circumference and the postoperative IOP gradually becomes controlled, compared with subjects receiving circumferential trabeculotomy alone.…”

“… 57 , 58 The expression of the factor promotes the commitment of developing tissues to lymphatic fate by budding from the veins to form the primitive lymph sac. 57 , 60 In addition, signaling through the vascular endothelial growth factor receptor-3, another lymphatic marker, is also involved in SC development. 59 Although SCEs do not express the lymphatic vessel endothelial hyaluronan receptor-1 or podoplanin, 56 – 59 they show high levels of CCL21, 61 which promotes lymphatic drainage.…”