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L. Chen, H. Zhang, D. Yuen; Combined Blockade of VEGFR-3 and VLA-1 Promotes High-Risk Corneal Transplant Survival. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1556.
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Though corneal transplantation enjoys a low rejection rate of 10% in uninflamed recipient corneas or "low-risk" setting, the rejection rate of corneal grafts on the inflamed and highly vascularized recipient corneas or "high-risk" setting can be as high as 90%. To date, there is no effective treatment for this condition. Previous studies have demonstrated that single treatment of VEGFR-3 (vascular endothelial growth factor receptor-3) or VLA-1 (very late antigen-1) suppressed corneal graft rejection in the "low-risk" setting. This study is to determine whether a combined blockade of VEGFR-3 and VLA-1 will promote "high-risk" transplant survival.
High-risk corneal transplantation was performed between normal C57BL/6 (donor) and inflamed BALB/c (recipient) mice. The recipients were randomized to receive intraperitoneal injection of the VEGFR-3 (provided by ImClone Systems, New York) and VLA-1 neutralizing antibodies (provided by Covella Pharmaceuticals, Inc.) or their controls twice a week on the day of suture placement and thereafter for 10 weeks. Corneal grafts were evaluated by ophthalmic slit-lamp biomicroscopy and analyzed by Kaplan-Meier survival curve.
Compared to those of the control group, the transplants in the treatment group demonstrated a greater degree of transparency and a higher rate of survival.
Combined blockade of VEGFR-3 and VLA-1 may provide a new strategy to promote high-risk corneal transplant survival. Further studies are undertaken to determine possible underlying mechanisms of this significant effect.
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