Abstract
Purpose :
Scar formation is the most common cause of glaucoma filtration surgery fails due to increased fibroblast proliferation and activation. The aim of this study, to elucidate the inhibitory effect of Y-27632, Rho-associated protein kinase inhibitor (ROCK), on post-surgical scarring formation in human tenon fibroblast (HTF).
Methods :
Collagen gel contraction assay was used to compare contractility activity of Y-27632 with various anti-glaucoma drug and to examine the effect of Y-27632 in combination with other anti-glaucoma drugs. To investigate the effect of Y-27632 in post-surgical scarring, we mimic the TGF-β secretion by inducing the cell with TGF-β prior to Y-27632. The effect of Y-27632 on latanoprost and timolol-induce contractions were also tested in this study. Immunofluorescence (IF) and western blot (WB) were used to study the expression of factors relating scarring formation.
Results :
Y-27632 inhibited contraction in collagen gel assay, which was inversely promoted by latanoprost, timolol or TGF-β. IF and WB analysis showed that latanoprost and timolol significantly enhanced the upregulation of α-SMA and vimentin while Y-27632 significantly suppressed those expressions. HTF cell culture in the presence of TGF-β significantly increased the gel contraction. In contrast, when the cell treated with 10 μM Y-27632, the contraction was significantly inhibited. Y-27632 also considerably inhibited contraction in latanoprost- and timolol-induce contraction.
Conclusions :
These results suggest that ROCK inhibitor may inhibit excessive fibrosis after glaucoma filtering surgery via inhibition the transdifferentiation of tenon fibroblast into myofibroblast. These results considering ROCK inhibitors may have a potential effect as anti-scarring for glaucoma filtration surgery.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.