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

Sci Rep. 2020 Sep 29;10(1):16040. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anterior Chamber / physiology
  • Aqueous Humor / metabolism
  • Glaucoma / metabolism
  • Growth Differentiation Factor 2 / metabolism*
  • Intraocular Pressure / physiology*
  • Lymphangiogenesis / physiology
  • Lymphatic Vessels / metabolism*
  • Lymphatic Vessels / physiology
  • Male
  • Membrane Transport Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Sclera / physiology
  • Tonometry, Ocular / methods
  • Trabecular Meshwork / physiology

Substances

  • Growth Differentiation Factor 2
  • Membrane Transport Proteins
  • Xlkd1 protein, mouse