The Role of Survivin and Transcription Factor FOXP1 in Scarring After Glaucoma Surgery

Abstract

Purpose This study aims to elucidate the role and mechanism of survivin and FOXP1 in scarring after glaucoma surgery and to evaluate the prevention and treatment of excessive wound healing and scar formation in an in vitro model of glaucoma filtration surgery. Methods Human Tenon's capsule fibroblasts (HTFs) were used with TGF-β to establish an in vitro cell model after glaucoma, observe survivin expression in the cell model, and observe HTFs proliferation after treatment with survivin inhibitor YM155 and the expression of α-SMA and collagen type I. In addition, the effects of survivin and cell proliferation in HTFs after knockdown of FOXP1 were observed by Western blot analysis. Results Survivin was upregulated in HTFs after glaucoma surgery, and it could promote the cell proliferation of HTFs. After treatment with its inhibitor YM155, the cell proliferation of HTFs was inhibited, and the expression of α-SMA and collagen type I were decreased. The results showed that in knockdown of FOXP1, the expression of survivin was downregulated, and the cell proliferation of HTFs was significantly reduced. Conclusions This study demonstrates that targeting survivin with an inhibitory YM155 reduced fibrosis and the extracellular matrix (ECM), and it was regulated by the FOXP1 transcription factor. These results suggest that survivin could be a potential target for treating scar formation after glaucoma surgery. Translational Relevance Together with the results from previous survivin and FOXP1 preclinical studies, these data support the evaluation of this gene therapy candidate in clinical trials as a potential durable treatment for antiscarring of glaucoma surgery.

Survivin regulates intracellular stiffness and extracellular matrix production in vascular smooth muscle cells

“…Furthermore, the stiffness-sensitive induction of ECM proteins was blocked when survivin expression was suppressed by YM155, indicating that survivin may serve as a signal to promote ECM production. These findings are consistent with other studies showing that downregulation of survivin reduces vessel wall thickness and neointima formation in response to vascular injury 80 and reduces collagen-1 in human Tenon's capsule fibroblasts 49 and hepatic stellate cells. 81 …”

Survivin Regulates Intracellular Stiffness and Extracellular Matrix Production in Vascular Smooth Muscle Cells

“…Furthermore, the stiffness-sensitive induction of ECM proteins was blocked when survivin expression was suppressed, indicating that survivin may serve as a signal to promote ECM production. These findings are consistent with other studies showing that downregulation of survivin reduces vessel wall thickness and neointima formation in response to vascular injury [61] and reduces collagen-1 in human Tenon's capsule fibroblasts [49] and hepatic stellate cells [62].…”