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

Aspelund, Aleksanteri, Tammela, Tuomas, Antila, Salli, Nurmi, Harri, Leppanen, Veli-Matti, Zarkada, Georgia, Stanczuk, Lukas, Francois, Mathias, Makinen, Taija, Saharinen, Pipsa, Immonen, Ilkka and Alitalo, Kari (2014) The Schlemm’s canal is a VEGF-C/VEGFR-3–responsive lymphatic-like vessel. The Journal of Clinical Investigation, 124 9: 3975-3986. doi:10.1172/JCI75395

Author Aspelund, Aleksanteri
Tammela, Tuomas
Antila, Salli
Nurmi, Harri
Leppanen, Veli-Matti
Zarkada, Georgia
Stanczuk, Lukas
Francois, Mathias
Makinen, Taija
Saharinen, Pipsa
Immonen, Ilkka
Alitalo, Kari
Title The Schlemm’s canal is a VEGF-C/VEGFR-3–responsive lymphatic-like vessel
Journal name The Journal of Clinical Investigation   Check publisher's open access policy
ISSN 0021-9738
Publication date 2014-09-02
Year available 2014
Sub-type Article (original research)
DOI 10.1172/JCI75395
Open Access Status DOI
Volume 124
Issue 9
Start page 3975
End page 3986
Total pages 12
Place of publication Ann Arbor, MI, United States
Publisher American Society for Clinical Investigation
Language eng
Abstract In glaucoma, aqueous outflow into the Schlemm’s canal (SC) is obstructed. Despite striking structural and functional similarities with the lymphatic vascular system, it is unknown whether the SC is a blood or lymphatic vessel. Here, we demonstrated the expression of lymphatic endothelial cell markers by the SC in murine and zebrafish models as well as in human eye tissue. The initial stages of SC development involved induction of the transcription factor PROX1 and the lymphangiogenic receptor tyrosine kinase VEGFR-3 in venous endothelial cells in postnatal mice. Using gene deletion and function-blocking antibodies in mice, we determined that the lymphangiogenic growth factor VEGF-C and its receptor, VEGFR-3, are essential for SC development. Delivery of VEGF-C into the adult eye resulted in sprouting, proliferation, and growth of SC endothelial cells, whereas VEGF-A obliterated the aqueous outflow system. Furthermore, a single injection of recombinant VEGF-C induced SC growth and was associated with trend toward a sustained decrease in intraocular pressure in adult mice. These results reveal the evolutionary conservation of the lymphatic-like phenotype of the SC, implicate VEGF-C and VEGFR-3 as critical regulators of SC lymphangiogenesis, and provide a basis for further studies on therapeutic manipulation of the SC with VEGF-C in glaucoma treatment.
Keyword Medicine, Research & Experimental
Research & Experimental Medicine
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID ERC-2010-AdG-268804
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 42 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 43 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Sat, 02 Aug 2014, 01:11:27 EST by Susan Allen on behalf of Institute for Molecular Bioscience