Eye lymphatic defects induced by bone morphogenetic protein 9 deficiency have no functional consequences on intraocular pressure

Mariela Subileau,Sabine Bailly,Alison Carret,Daniel Vittet,Isabelle Vilgrain,Niyazi Acar,Lionel Bretillon

doi:10.1038/s41598-020-71877-z

Abstract

Aqueous humor drainage is essential for the regulation of intraocular pressure (IOP), a major risk factor for glaucoma. The Schlemm’s canal and the non-conventional uveoscleral pathway are known to drain aqueous humor from the eye anterior chamber. It has recently been reported that lymphatic vessels are involved in this process, and that the Schlemm’s canal responds to some lymphatic regulators. We have previously shown a critical role for bone morphogenetic protein 9 (BMP9) in lymphatic vessel maturation and valve formation, with repercussions in drainage efficiency. Here, we imaged eye lymphatic vessels and analyzed the consequences of Bmp9 (Gdf2) gene invalidation. A network of lymphatic vessel hyaluronan receptor 1 (LYVE-1)-positive lymphatic vessels was observed in the corneolimbus and the conjunctiva. In contrast, LYVE-1-positive cells present in the ciliary bodies were belonging to the macrophage lineage. Although enlarged conjunctival lymphatic trunks and a reduced valve number were observed in Bmp9-KO mice, there were no morphological differences in the Schlemm’s canal compared to wild type animals. Moreover, there were no functional consequences on IOP in both basal control conditions and after laser-induced ocular hypertonia. Thus, the BMP9-activated signaling pathway does not constitute a wise target for new glaucoma therapeutic strategies.

Highlights

Glaucoma is a group of neuropathies associated with retinal ganglion cells and optic nerve degeneration that can lead to severe vision loss
To address the potential consequences of Bmp[9] gene invalidation on eye lymphatics and on aqueous humor drainage and intraocular pressure (IOP), we first characterized the distribution of the lymphatic vessels of the mouse eye
Their expression profiles are in accordance with the presence of both classical M1 and alternative M2 macrophage subtypes according to their CD206 antigen expression pattern[47]

Summary

Introduction

Glaucoma is a group of neuropathies associated with retinal ganglion cells and optic nerve degeneration that can lead to severe vision loss. Following binding to prostaglandin FP receptors, their effects were described to be mainly related with the rapid induced relaxation of both ciliary muscle cells and trabecular meshwork cells, and further extracellular matrix remodeling after metalloproteinases synthesis Another more recent work mentioned that Latanoprost have reduced IOP-lowering effects in patients who have undergone cervical lymph node s urgery[21]. Overall, these observations support the hypothesis of the involvement of a lymphatic component in aqueous humor outflow regulation. The consequences of Bmp[9] gene invalidation in the mouse were still observed in the skin and the diaphragm of adult mice in parallel of a reduced lymphatic drainage efficiency in limb[37]

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Conclusion