• Home
  • Search Results
  • The Schlemm's canal is a VEGF-C/VEGFR-3-responsive lymphatic-like vessel.

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

The Journal of clinical investigation (2014-07-26)
Aleksanteri Aspelund, Tuomas Tammela, Salli Antila, Harri Nurmi, Veli-Matti Leppänen, Georgia Zarkada, Lukas Stanczuk, Mathias Francois, Taija Mäkinen, Pipsa Saharinen, Ilkka Immonen, Kari Alitalo
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
DAPI, for nucleic acid staining
Sigma-Aldrich
Glutaraldehyde solution, Grade I, 25% in H2O, specially purified for use as an electron microscopy fixative
Sigma-Aldrich
Glutaraldehyde solution, Grade II, 25% in H2O
Sigma-Aldrich
Imidazole, ACS reagent, ≥99% (titration)
Sigma-Aldrich
Glutaraldehyde solution, 50 wt. % in H2O
Sigma-Aldrich
Imidazole, for molecular biology, ≥99% (titration)
Sigma-Aldrich
Imidazole, ReagentPlus®, 99%
Sigma-Aldrich
Imidazole, puriss. p.a., ≥99.5% (GC)
Sigma-Aldrich
Glutaraldehyde solution, Grade I, 50% in H2O, specially purified for use as an electron microscopy fixative or other sophisticated use
Sigma-Aldrich
Imidazole buffer Solution, BioUltra, 1 M in H2O
Sigma-Aldrich
Glutaraldehyde solution, Grade I, 70% in H2O, specially purified for use as an electron microscopy fixative or other sophisticated use
Sigma-Aldrich
Imidazole, BioUltra, ≥99.5% (GC)
Sigma-Aldrich
Anti-NG2 Chondroitin Sulfate Proteoglycan Antibody, Chemicon®, from rabbit
Sigma-Aldrich
Imidazole, anhydrous, free-flowing, Redi-Dri, ACS reagent, ≥99%
Sigma-Aldrich
Imidazole, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
Glutaraldehyde solution, Grade I, 8% in H2O, specially purified for use as an electron microscopy fixative or other sophisticated use
Supelco
Imidazole, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Imidazole, ≥99% (titration), crystalline
Sigma-Aldrich
Glutaraldehyde solution, 50% in H2O, suitable for photographic applications
Sigma-Aldrich
Anti-PECAM-1 Antibody, clone 2H8, Azide Free, clone 2H8, Chemicon®, from hamster(Armenian)
Sigma-Aldrich
Glutaraldehyde solution, technical, ~50% in H2O (5.6 M)
Sigma-Aldrich
Glutaric dialdehyde solution, 50 wt. % in H2O, FCC
USP
Imidazole, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Imidazole, ReagentPlus®, 99%, Redi-Dri, free-flowing
Ondansetron impurity E, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Anti-VCAN antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-CSPG4 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Imidazole, for molecular biology, ≥99% (titration), free-flowing, Redi-Dri
Imidazole, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Anti-CSPG4 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution