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K. Terai, J. Yamada, S. Kinoshita; The Effects of Tgf-Beta Signaling Inhibitor in Cat Corneal Endothelium. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2844.
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We have reported that inhibition of TGF-beta signaling accelerates proliferation of mouse corneal endothelial cells in vivo by using a mouse corneal endothelium injury model. However, those results may not directly adapt to human corneas because mouse corneal endothelial cells have a higher proliferative ability than those in humans and can regenerate even when almost all of the cells are removed. The purpose of this study was to confirm the effect of TGF-beta signaling inhibitor in the corneal endothelium of cats, as the proliferative ability of cat corneal endothelial cells is similar to that in humans.
The corneal endothelia of cats were injured by either 1) liguid-nitrogen cryo injury from the epithelial side, 2) intracameral injection of 0.01% benzalkonium chloride, or 3) mechanical removal. In those endothelia,, 10 ug/mL of TGF-beta receptor-1 kinase inhibitor (CALBIOCHEM, 616451) was injected intracamerally after injury, yet some injured endothelia were injected with only PBS as a control. The TGF- beta signal inhibition groups and the controls were then compared.
Of the TGF-beta signal inhibition groups, alizarin red staining in the liquid-nitrogen cryo-injury group showed that endothelial cell density was significantly higher than in the control group, however, that cryo-injury also injured the corneal stroma and thus may not be an ideal model. In the group injured by intracameral injection of 0.01% benzalkonium chloride, corneal transparency gradually recovered for 6 months and was clearer than in the controls. However, that injury induced long- term bullous keratopathy, so it may not be an ideal model. The mechanical removal injury required a more difficult technique than the others, but it may be the best method. At 3 and 7 days after injury, it was confirmed that proliferation of the corneal endothelial cell was up-regulated in the TGF-beta signal inhibition group by analysis of Bromodeoxyuridine (BrdU) incorporation.
These results suggest that TGF-beta signal inhibition is effective in a cat corneal endothelial injury model, yet further data is needed to discover if that inhibition is effective enough for clinical application.
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