Preliminary antifibrotic and vasoconstrictor effects of adrenaline in Schlemm's canal and suprachoroidal minimally invasive glaucoma surgery in primary open-angle glaucoma.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2024-09-30 DOI:10.1007/s00417-024-06642-3
Jinyuan Luo, Julia Fajardo-Sanchez, Mengqi Qin, Brihitejas Patel, Karishma Mahtani, Henrietta Ho, Cynthia Yu-Wai-Man
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Abstract

Purpose: To investigate the antifibrotic and vasoconstrictor effects of adrenaline in Schlemm's canal and suprachoroidal minimally invasive glaucoma surgery (MIGS).

Methods: Human trabecular meshwork (TM) cells were treated with different concentrations of adrenaline (0%, 0.0005%, 0.01%), and we measured the effects on contractility, cell viability and the expression of key cell cycle and fibrosis genes. Adrenaline 0.05% was also injected intracamerally in five primary open-angle glaucoma patients undergoing iStent inject or MINIject surgery combined with phacoemulsification. All patients were assessed for ocular and systemic adverse reactions, including the effects on intraoperative pupil size, preoperative and postoperative visual acuity, intraocular pressure, and anterior segment OCT results.

Results: Adrenaline significantly reduced the contractility of TM cells in a dose-dependent manner (87.8%, 80.6%, 7.9% matrix contraction with adrenaline 0%, 0.0005%, 0.01%, respectively). Adrenaline did not exhibit any significant cytotoxicity even at high concentrations (P > 0.05). Adrenaline 0.01% significantly downregulated the expression of key cell cycle genes in the G2 and M phases, and also decreased the expression of MRTFB and ACTA2 genes (P < 0.05). Intracameral injections of adrenaline 0.05% in the five MIGS patients did not result in any ocular or systemic adverse effects.

Conclusion: We recommend intracameral injections of adrenaline 0.05% as a cheap and safe drug to be used before MIGS insertion. Adrenaline decreases the risk of bleeding from the trabecular meshwork and also exhibits antifibrotic effects by arresting the cell cycle, thereby increasing the postoperative success rates in MIGS.

Key message: What is known Fibrosis is the main cause of surgical failure in minimally invasive glaucoma surgery (MIGS). Mitomycin-C and 5-fluorouracil are too toxic to be used inside the eye. What is new Adrenaline reduced the contractility of trabecular meshwork cells and inhibited the expression of key cell cycle genes and fibrosis genes, without significant cytotoxicity. Intracameral injection of adrenaline 0.05% did not result in any ocular or systemic adverse reactions in MIGS patients.

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肾上腺素在原发性开角型青光眼 Schlemm's 管和脉络膜上微创青光眼手术中的初步抗纤维化和血管收缩作用。
目的:研究肾上腺素在Schlemm's管和脉络膜上微创青光眼手术(MIGS)中的抗纤维化和血管收缩作用。方法:用不同浓度的肾上腺素(0%、0.0005%、0.01%)处理人小梁网(TM)细胞,测量其对收缩力、细胞活力以及关键细胞周期和纤维化基因表达的影响。我们还为五名接受 iStent 注射或 MINIject 手术并结合超声乳化术的原发性开角型青光眼患者在晶体内注射了 0.05% 的肾上腺素。对所有患者的眼部和全身不良反应进行了评估,包括对术中瞳孔大小、术前和术后视力、眼压和前段 OCT 结果的影响:肾上腺素以剂量依赖的方式明显降低了 TM 细胞的收缩力(肾上腺素 0%、0.0005%、0.01% 时基质收缩率分别为 87.8%、80.6%、7.9%)。即使在高浓度下,肾上腺素也没有表现出明显的细胞毒性(P > 0.05)。肾上腺素 0.01% 能显著下调 G2 期和 M 期关键细胞周期基因的表达,还能降低 MRTFB 和 ACTA2 基因的表达(P 结论:肾上腺素 0.01% 能显著下调 G2 期和 M 期关键细胞周期基因的表达,还能降低 MRTFB 和 ACTA2 基因的表达:我们建议在插入 MIGS 前巩膜内注射 0.05% 肾上腺素,这是一种既便宜又安全的药物。肾上腺素能降低小梁网出血的风险,还能通过阻止细胞周期而发挥抗纤维化作用,从而提高 MIGS 的术后成功率:已知纤维化是微创青光眼手术(MIGS)失败的主要原因。丝裂霉素-C和5-氟尿嘧啶毒性太大,不能在眼内使用。新发现 肾上腺素能降低小梁网细胞的收缩力,抑制关键细胞周期基因和纤维化基因的表达,且无明显细胞毒性。鞘内注射 0.05% 肾上腺素不会导致 MIGS 患者出现任何眼部或全身不良反应。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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