Department of Ophthalmology, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing 401120, China.
Institute of Rocket Force Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Third Military Medical University, Chongqing 400038, China.
Aging (Albany NY). 2020 May 23;12(10):8837-8857. doi: 10.18632/aging.102997.
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.
青光眼滤过手术（GFS）是治疗眼压（IOP）控制不佳的青光眼的有效临床治疗方法。然而，手术部位结膜瘢痕的发生是手术失败的主要原因。在之前的研究中，我们通过指数富集的配体系统进化（SELEX）分离并开发了针对 TβR II 的新型核酸适体 S58。在这里，我们展示了 S58 如何通过空间位阻抑制 TβR II 与 TGF-β 的相互作用。我们在兔 GFS 模型中研究了局部 S58 治疗的效果。在术后 6 周，S58 减少了 GFS 后兔子的纤维化并延长了滤泡的存活时间。进一步的体外试验表明，S58 处理的人结膜成纤维细胞（HConFs）中的纤维化水平降低，抗氧化防御能力增强。此外，核因子红细胞 2 相关因子 2（Nrf2）的缺失或磷酸肌醇 3-激酶/蛋白激酶 B（PI3K/Akt）的抑制逆转了 S58 的抗纤维化作用。本工作表明，S58 可以通过激活细胞内抗氧化防御 PI3K/Akt/Nrf2 信号通路，有效改善 GFS 手术效果。
