Research Paper Volume 12, Issue 10 pp 8837—8857
The TβR II-targeted aptamer S58 prevents fibrosis after glaucoma filtration surgery
- 1 Department of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing 401120, China
- 2 Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, China
Received: October 13, 2019 Accepted: February 4, 2020 Published: May 23, 2020https://doi.org/10.18632/aging.102997
How to Cite
Copyright © 2020 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Glaucoma filtration surgery (GFS) is an effective clinical treatment for glaucoma when intraocular pressure (IOP) control is poor. However, the occurrence of conjunctival scarring at the surgical site is the main reason for failure of the surgery. In a previous study, we isolated and developed S58, a novel nucleic acid aptamer targeting TβR II, by systematic evolution of ligands by exponential enrichment (SELEX). Here, we show how S58 sterically inhibits the TβR II interaction with TGF-β. The effects of topical S58 treatment were studied in a rabbit model of GFS. At 6 postoperative weeks, S58 reduced fibrosis and prolonged bleb survival in rabbits after GFS. Further in vitro tests showed that the levels of fibrosis in S58 treated-Human Conjunctival Fibroblasts (HConFs) were decreased and that antioxidant defense was increased. In addition, the loss of nuclear factor erythroid 2-related factor 2 (Nrf2) or the inhibition of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) reversed the anti-fibrotic effects of S58. The present work suggests that S58 could effectively improve GFS surgical outcomes by activating the intracellular antioxidant defense PI3K/Akt/Nrf2 signaling pathway.
S58: Aptamer S58; TGF-β2: Transforming growth factor beta; TβR II: TGF-β Receptor II; SELEX: systematic evolution of ligands by exponential enrichment; CCK8: Cell counting kit-8; qPCR: quantitative polymerase chain reaction; EMT: Epithelial-Mesenchymal Transition; HConFs: Human Conjunctival Fibroblasts; Nrf2 and PI3K/Akt: nuclear factor erythroid 2-related factor 2 (Nrf2) and phosphoinositide 3-kinase/protein kinase B; SOD: Superoxide dismutase; GFS: Glaucoma Filtration Surgery; NOX-4: NADPH oxidase 4; PBS: Phosphate Buffer solution; γ-GCS: γ-glutamyl cysteine synthetase; CAT: Catalase; IOP: Intraocular pressure.