Dataset Information

The T?R II-targeted aptamer S58 prevents fibrosis after glaucoma filtration surgery.

ABSTRACT: 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 T?R II, by systematic evolution of ligands by exponential enrichment (SELEX). Here, we show how S58 sterically inhibits the T?R II interaction with TGF-?. 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.

SUBMITTER: Li X

PROVIDER: S-EPMC7288943 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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The TβR II-targeted aptamer S58 prevents fibrosis after glaucoma filtration surgery.

Li Xueru X Leng Yu Y Li Xiangji X Wang Yawei Y Luo Peng P Zhang Chi C Wang Ziwen Z Yue Xiaofeng X Shen Chongxing C Chen Long L Liu Zujuan Z Shi Chunmeng C Xie Lin L

Aging 20200523 10

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 ef ...[more]

PMID: 32452828

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Project description:PrcisUtilizing an automated pipeline for data extraction from electronic health records provides real-world information on the success of various glaucoma procedures, with tube shunt implantation associated with increased failure rates compared with trabeculectomy.BackgroundWe aimed to evaluate the long-term survival of glaucoma surgeries using an automated pipeline for extraction of outcomes from electronic health records.MethodsA retrospective observational study from a single academic center. Patients undergoing trabeculectomy, Ex-PRESS shunt, Baerveldt, and Ahmed tube shunt insertion from 2009 to 2018 were identified from electronic health record procedure codes. Patient characteristics were identified from structured and unstructured fields using a previously validated natural language processing pipeline.ResultsFive hundred twelve patients underwent 711 glaucoma surgeries: 287 trabeculectomies, 47 Ex-PRESS shunts, 274 Baerveldt and 103 Ahmed tube implantations. The Median follow-up was 359 days. The mean baseline IOP was 24.4 mm Hg (SD 10.9), and 73.1% were on ≥3 medications. Compared with trabeculectomy, tube shunt surgery had a higher risk of failure (Baerveldt: Hazard Ratio (HR) 1.44, 95% CI 1.02 to 2.02; Ahmed: HR 2.01, 95% CI 1.28 to 3.17). Previous glaucoma surgery was associated with increased failure (≥2 previous surgeries: HR 2.74, 95% CI 1.62 to 4.64), as were fewer baseline medications (<3 medications: HR 2.96, 95% CI 2.12 to 4.13) and male sex (HR 1.40, 95% CI 1.03 to 1.90). At 1 year, tube shunt patients had a 2.53 mm Hg ( P =0.002) higher IOP compared with trabeculectomy patients.ConclusionsBaerveldt and Ahmed tube shunt implantation was associated with increased failure compared with trabeculectomy. Fewer baseline medications, previous glaucoma surgeries, and male sex were also risk factors for failure. These results demonstrate the utility of applying an informatics pipeline to electronic health records to investigate key clinical questions using real-world evidence.

Dataset Information

The T?R II-targeted aptamer S58 prevents fibrosis after glaucoma filtration surgery.

Publications

The TβR II-targeted aptamer S58 prevents fibrosis after glaucoma filtration surgery.

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