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S. Grimaldo, D. Yuen, L. Chen; Vla-1 is Directly Involved in Lymphangiogenesis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):34.
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In the inflamed and lymphatic-rich corneas, the transplantation rejection rate can be as high as 90%. Unfortunately, many patients who are blind from corneal diseases fall in this category after inflammatory, traumatic, or chemical insults. To date, there is no effective treatment for these patients. This study is to investigate the specific roles of VLA-1 (very late antigen 1; also known as alpha1beta1 integrin) in the processes of lymphangiogenesis both in vitro and in vivo.
In vitro human lymphatic endothelial cell (LEC) culture model was used to study the expression of VLA-1 in LECs by both RT-PCR and immunocytochemistry assays. The effect of VLA-1 depletion in LECs by small interference RNAs (siRNA) on LEC proliferation and tube formation were also analyzed. Additionally, murine in vivo suture-induced corneal inflammatory lymphangiogenesis model was used to study the effect of VLA-1 neutralizing antibody (provided by Covella Pharmaceuticals, Inc.) on the development of new lymphatic vessels in the inflamed corneas.
VLA-1 was expressed in human LECs at both mRNA and protein levels. Its down-regulation by siRNAs suppressed LEC proliferation as well as tube formation. This effect was also confirmed in the inflamed corneas after the antibody treatment.
VLA-1 plays a direct role in the processes of lymphangiogenesis, holding the promise of uncovering new therapeutic targets for corneal inflammation and transplant rejection. It is hopeful that beyond its contributions to eye diseases, this study also will shed some light on the development of new therapeutic strategies for other lymphatic-related disorders in the body.
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