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

Abstract

Schlemm's canal (SC) is a unique vascular structure that functions to maintain fluid homeostasis by draining aqueous humor from the eye into the systemic circulation. The endothelium lining the inner wall of SC has both blood and lymphatic vascular characteristics, thus prompting exploration of the development and regulation of this unique channel. In this issue of the JCI, back-to-back papers by Aspelund et al. and Park et al. detail the mechanisms of SC development, which includes a lymphatic reprogramming that is necessary to maintain proper function. Furthermore, both groups exploit the lymph-like qualities of this canal: they identify VEGF-C as a potential therapeutic for glaucoma and suggest that expression of PROX1, a marker of lymphatic fate, could also serve as a biosensor for monitoring SC integrity. These studies provide substantial insight into the molecular and cellular pathways that govern SC development and reveal that ocular pathology is associated with deregulation of the lymph-like characteristics of SC.

Figure 1. Optical projection tomography (OPT) reconstruction of a mouse eye.

Whole-mount immunostaining with LYVE-1 reveals corneolimbal lymphatic vessels (clv) on the backdrop of OPT autofluorescence. SC (LYVE-1 negative) is illustrated in green at the corneoscleral junction. Red and blue arrows denote the two drainage pathways for vitreous humor (vh), originating from the ciliary body (cb). Low-dose VEGF-C therapy stimulates proliferation of SC and improves aqueous humor drainage pathways. Normal and pathological eye phenotypes are contrasted; asterisks denote vascular marker staining specific to SC. c, cornea; ac, anterior chamber; pc, posterior chamber; eom, extraocular muscle; on, optic nerve; SMA, smooth muscle actin. Image credit: S.T. Espenschied.