Regulation of blood vessel versus lymphatic vessel growth in the cornea.

Journal Article (Journal Article)

PURPOSE: In the present study, the authors developed novel models to stimulate blood vessel formation (hemangiogenesis) versus lymphatic vessel formation (lymphangiogenesis) in the cornea. METHODS: Micropellets loaded with high-dose (80 ng) or low-dose (12.5 ng) basic fibroblast growth factor (bFGF) were placed in BALB/c corneas. Angiogenic responses were analyzed by immunohistochemistry to quantify blood neovessels (BVs) and lymphatic neovessels (LVs) to 3 weeks after implantation. Areas covered by BV and LV were calculated and expressed as a percentage of the total corneal area (percentage BV and percentage LV). Hemangiogenesis (HA) and lymphangiogenesis (LA) were also assessed after antibody blockade of VEGFR-2 or VEGFR-3 RESULTS: Although high-dose bFGF stimulation induced a more potent angiogenic response, the relative LV (RLV=percentage LV/percentage BV x 100) was nearly identical with high- and low-doses of bFGF. Delayed LA responses induced 3 weeks after implantation of high-dose bFGF resulted in a lymphatic vessel-dominant phenotype. Interestingly, the blockade of VEGFR-2 significantly suppressed BV and LV. However, the blockade of VEGFR-3 inhibited only LV (P=0.0002) without concurrent inhibition of BV (P=0.79), thereby resulting in a blood vessel-dominant phenotype CONCLUSIONS: An HA-dominant corneal phenotype can be obtained in BALB/c mice 2 weeks after implantation of an 80-ng bFGF micropellet with VEGFR-3 blockade. Alternatively, an LA-dominant corneal phenotype can be obtained 3 weeks after implantation of an 80-ng bFGF micropellet without supplementary modulating agents. These models will be useful in evaluating the differential contribution of BV and LV to a variety of corneal abnormalities, including transplant rejection, wound healing and microbial keratitis.

Full Text

Duke Authors

Cited Authors

  • Chung, E-S; Saban, DR; Chauhan, SK; Dana, R

Published Date

  • April 2009

Published In

Volume / Issue

  • 50 / 4

Start / End Page

  • 1613 - 1618

PubMed ID

  • 19029028

Pubmed Central ID

  • PMC2702143

Electronic International Standard Serial Number (EISSN)

  • 1552-5783

Digital Object Identifier (DOI)

  • 10.1167/iovs.08-2212


  • eng

Conference Location

  • United States