The Schlemm’s canal is a VEGF-C/VEGFR-3–responsive lymphatic-like vessel

Schlemm’s canal: more than meets the eye, lymphatics in disguise

“…Importantly, both Park et al and Aspelund et al confirmed PROX1 expression in SC (14,15), reinforcing its lymphatic fate characteristics. Immunohistochemical staining to characterize the ECs of SC revealed that they were positive for certain lymphatic and blood endothelial markers, including PROX1, integrin α9, CD31, lin, exhibited corneal edema, inflammation, and dilated corneoscleral lymphatic vessels (12).…”

“…Earlier this year, Truong et al discovered high expression of the lymphatic transcription factor prospero-related homeobox 1 (PROX1) on SC endothelium in the eye (13), linking expression of the lymphatic fate determinant PROX1 to a structure within the eye. In this issue of JCI, two independent yet complementary studies by Park et al (14) and Aspelund et al (15) use genetic mouse models and sophisticated lymphatic imaging techniques to offer insight into the developmental origin of SC and the pathology associated with its improper regulation.…”

“…In contrast, adenoviral or adeno-associated virus (AAV) delivery of VEGF-A induced massive increases in IOP and obliterated SC (15). These contrasting results of VEGF-mediated vascular growth in the eye are perhaps best explained by the observation that the preferential VEGF-C receptor, VEGFR3, is restricted to the ECs of SC, while the canonical VEGF-A receptor, VEGFR2, is ubiquitously expressed throughout the vascular structures of the eye.…”

Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity

“…While IOP is influenced by both production and drainage of the AH, defects in anterior chamber outflow have been identified as the source of ocular hypertension in glaucoma patients, including PCG patients (5,46). Despite evidence that vascular growth factors are essential for SC development and AH outflow (25,31,47), links between these pathways and human glaucoma have not been identified. Herein, we describe 10 heterozygous novel/rare protein-altering mutations in TEK as a cause for PCG.…”

Open-angle glaucoma: therapeutically targeting the extracellular matrix of the conventional outflow pathway

“…It is also distinct from other vessels in its ability to form giant vacuoles under high pressure and its unique tight junction profile including claudin-11 [43]. These features have allowed for new therapeutic opportunities to arise, such as the use of the VEGF family in outflow facility modulation [44,45]. The basement membrane is a fibrous layer of ECM material separating the endothelium from underlying connective tissues.…”