June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Galectin-3 Inhibition by A Small-Molecule Inhibitor Reduces Both Pathological Corneal Neovascularization and Fibrosis

Author Affiliations & Notes
  • Noorjahan A Panjwani
    Ophthalmology, Tufts University Medical School, Boston, Massachusetts, United States
  • Zhiyi Cao
    Ophthalmology, Tufts University Medical School, Boston, Massachusetts, United States
  • Wei-Sheng Chen
    Ophthalmology, Tufts University Medical School, Boston, Massachusetts, United States
  • Hakon leffler
    Laboratory Medicine, Lund University, Lund, Sweden
  • Ulf J Nilsson
    Chemistry, Lund University, Lund, Sweden
  • Footnotes
    Commercial Relationships   Noorjahan Panjwani, None; Zhiyi Cao, None; Wei-Sheng Chen, None; Hakon leffler, Galecto Biotech (C); Ulf Nilsson, Galecto Biotech (C)
  • Footnotes
    Support  R01EY007088, R01EY009349, Mass Lions Eye Research fund, New England Corneal Transplant Fund, an unrestricted award from Research to Prevent Blindness, and Galecto Biotech.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 996. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Noorjahan A Panjwani, Zhiyi Cao, Wei-Sheng Chen, Hakon leffler, Ulf J Nilsson; Galectin-3 Inhibition by A Small-Molecule Inhibitor Reduces Both Pathological Corneal Neovascularization and Fibrosis

      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):996.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : Corneal neovascularization and scarring commonly lead to significant vision loss. This study was designed to determine whether a small molecule inhibitor of galectin-3 can inhibit both corneal angiogenesis and fibrosis in experimental mouse models.

Methods : Animal models of silver nitrate cautery and alkaline burn were used to induce mouse corneal angiogenesis and fibrosis, respectively. Corneas were treated with the galectin-3 inhibitor, 33DFTG, or vehicle alone and were processed for whole-mount immunofluorescence staining and Western blot analysis to quantify the density of blood vessels and markers of fibrosis. In addition, human umbilical vein endothelial cells (HUVECs) and primary human corneal fibroblasts were used to analyze the role of galectin-3 in the process of angiogenesis and fibrosis in vitro.

Results : Robust angiogenesis was observed in silver nitrate-cauterized corneas on day 5 post-injury and markedly increased corneal opacification was demonstrated in alkaline burn-injured corneas on days 7 and 14 post-injury. Treatment with the inhibitor substantially reduced corneal angiogenesis and opacification with a concomitant decrease in α-smooth muscle actin (α-SMA) expression and distribution. In vitro studies revealed that 33DFTG inhibited VEGF-A-induced HUVEC migration and sprouting without cytotoxic effects. The addition of exogenous galectin-3 to corneal fibroblasts in culture induced the expression of fibrosis-related proteins, including α-SMA and connective tissue growth factor.

Conclusions : Our data provide proof-of-concept that targeting galectin-3 by the novel, small molecule inhibitor, 33DFTG, ameliorates pathological corneal angiogenesis as well as fibrosis. These findings suggest a potential new therapeutic strategy for treating ocular disorders related to pathological angiogenesis and fibrosis.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×