Abstract
Purpose: :
Podoplanin has been shown to be a reliable marker of lymphatic endothelium, but its role in the lymphatic system has not been well investigated. We investigated the role of podoplanin in lymphangiogenesis in models of murine corneal transplantation and corneal inflammation (suture model) by testing the effect of blocking podoplanin on lymphatic growth in both models.
Methods: :
Male C57BL/6 mice (8-10 weeks old) were used as donors and male BALB/c mice (8-10 weeks old) were used as hosts for the corneal transplantation model. For a model of corneal inflammation, stromal incisions that encompassed more than 120 degrees of the corneal circumference were made and three 11-0 nylon sutures were placed intrastromally (each group, n=5). Rabbit anti- mouse podoplanin antisera (150 µg) (n=15) or rabbit IgG (n=9) were injected into the subconjuncitival space at 0, 3, 5, and 7 days after corneal transplantation at the time of suture placement and three days after suture placement. The status of the corneal transplant was assessed at postoperative day 56. Lymphatic vessels were visualized at postoperative day seven for the suture placement model when corneas were collected and stained with anti-LYVE-1. The area covered by vessels was determined using National Institutes of Health (NIH) image software.
Results: :
Administration of anti-podoplanin reduced lymphangiogenesis in the corneas of in the suture placement model (P<0.05) and led to a significant suppression of the rejection reaction in corneal transplantation model (85% vs control 40% survival rate; p=0.0259).
Conclusions: :
Blocking podoplanin inhibits lymphatic growth associated with corneal wound healing. These data functionally implicate podoplanin in the process of lymphangiogenesis and suggest a novel therapeutic target for high risk corneal transplantation. This work was supported by KAKENHI 19791283 and grant R21 EY018347 (PAD).
Keywords: neovascularization • cornea: basic science • transplantation