Abstract
Purpose :
Corneal neovascularization and scarring are serious conditions that can lead to a profound decline in vision or vision loss. Recent studies have demonstrated that a carbohydrate-binding protein, galectin-3 (Gal-3), promotes angiogenesis as well as fibrosis, and that it does so by independent mechanisms. Therefore, our goal has been to target Gal-3 for developing dual-benefit drugs to control both neovascularization and fibrosis of ocular tissues. We have recently synthesized a new small molecule inhibitor of Gal-3 (Gal-200-10) with improved properties including high Gal-3 selectivity. The Aim of the current study was to test the efficacy of this newly developed inhibitor in reducing corneal neovascularization and fibrosis.
Methods :
Corneal neovascularization was induced by silver nitrate (AgNO3) cautery and corneal fibrosis was induced by alkali-burn injury in C57B/6 mice. Vehicle alone (10µl of 1.65% hydroxyethyl cellulose) or GAL-200-10 (10µl in vehicle) were topically applied to the eye twice per day from day 1 until day 13. Corneal opacity was scored by slit lamp examination at day 7 and 14 post-injury. Corneas were harvested on day 7 (for angiogenesis analysis, whole mount staining with CD31, a marker of blood vessels) or 14 post-injury and processed for Western blotting and immunofluorescence staining with anti-α-SMA antibody to reveal and quantify the extent fibrosis in the treated and control groups.
Results :
Robust angiogenesis was observed in silver nitrate–cauterized corneas on day 7 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 (n=20, p<0.01, 31% inhibition compared to control) and opacification with a concomitant decrease in a-smooth muscle actin (a-SMA) expression and distribution (0.6677 ± 0.04921, n=3, p<0.01).
Conclusions :
The small molecule inhibitor, GAL-200-10, is an ideal candidate for developing a dual-benefit drug to control both corneal neovascularization and fibrosis.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.