| Autor: |
Jennifer C, Fan Gaskin, Roy C K, Kong, Manisha H, Shah, Amanda J, Edgley, Hitesh M, Peshavariya, Elsa C, Chan |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Translational Vision Science & Technology. 11:18 |
| ISSN: |
2164-2591 |
| DOI: |
10.1167/tvst.11.8.18 |
| Popis: |
Cytotoxic agents such as mitomycin C (MMC) are part of the mainstay treatment for limiting subconjunctival scarring following glaucoma filtration surgery (GFS). However, a safer antifibrotic therapy is clinically needed. The anti-scarring properties of 3',4'-dihydroxyflavonol (DiOHF) were evaluated in a mouse model of GFS and in cultured human Tenon's fibroblasts (HTFs).GFS was performed in C57BL/6 mice receiving daily intraperitoneal injections of DiOHF or vehicle or a single intraoperative injection of MMC. Eyes were harvested on day 14 for assessment of collagen deposition, expression of alpha-smooth muscle actin (α-SMA), cluster of differentiation 31 (CD31), and 4-hydroxy-2-nonenal (4HNE) in the conjunctiva/Tenon's layer. The inhibitory effects of DiOHF on transforming growth factor β (TGFβ)-induced responses were also assessed in HTFs.Treatment with DiOHF demonstrated a reduction in collagen deposition at the GFS site compared to vehicle-treated mice. The degree of 4HNE-positive fluorescence was significantly reduced in DiOHF-treated eyes compared to the other groups, indicating a decrease in oxidative stress. A reduction in expression of α-SMA and CD31 was seen in DiOHF-treated conjunctiva compared to those treated with vehicle. Concordant results were demonstrated in cultured HTFs in vitro. Furthermore, treatment of cultured HTFs with DiOHF also displayed a reduction in the proliferation, migration, and contractility of HTFs.Treatment with DiOHF reduces scarring and angiogenesis in the conjunctiva of mice with GFS at a level comparable to MMC. The reduction in oxidative stress suggests that DiOHF may suppress scarring via different mechanisms from MMC.DiOHF may be a safer and superior wound modulating agent than conventional antifibrotic therapy in GFS. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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