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肾上腺素在原发性开角型青光眼施累姆管及脉络膜上腔微创青光眼手术中的初步抗纤维化和血管收缩作用

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

作者信息

Luo Jinyuan, Fajardo-Sanchez Julia, Qin Mengqi, Patel Brihitejas, Mahtani Karishma, Ho Henrietta, Yu-Wai-Man Cynthia

机构信息

Faculty of Life Sciences & Medicine, King's College London, London, SE1 7EH, UK.

Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.

出版信息

Graefes Arch Clin Exp Ophthalmol. 2025 Feb;263(2):489-500. doi: 10.1007/s00417-024-06642-3. Epub 2024 Sep 30.

DOI:10.1007/s00417-024-06642-3
PMID:39347799
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11868348/
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.

摘要

目的

研究肾上腺素在施莱姆管和脉络膜上腔微创青光眼手术(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,测量其对细胞收缩性、细胞活力以及关键细胞周期和纤维化基因表达的影响。对5例接受iStent注射或MINIject手术联合超声乳化术的原发性开角型青光眼患者进行前房内注射0.05%肾上腺素。评估所有患者的眼部和全身不良反应,包括对术中瞳孔大小、术前和术后视力、眼压以及眼前节光学相干断层扫描(OCT)结果的影响。

结果

肾上腺素以剂量依赖性方式显著降低TM细胞的收缩性(肾上腺素浓度为0%、0.0005%、0.01%时,基质收缩分别为87.8%、80.6%、7.9%)。即使在高浓度下,肾上腺素也未表现出任何显著的细胞毒性(P>0.05)。0.01%的肾上腺素显著下调G2和M期关键细胞周期基因的表达,同时降低MRTFB和ACTA2基因的表达(P<0.05)。对5例MIGS患者进行前房内注射0.05%肾上腺素未导致任何眼部或全身不良反应。

结论

我们建议在前房内注射0.05%肾上腺素,作为一种廉价且安全的药物,在植入MIGS之前使用。肾上腺素可降低小梁网出血风险,并通过阻断细胞周期发挥抗纤维化作用,从而提高MIGS术后成功率。

关键信息

已知情况:纤维化是微创青光眼手术(MIGS)手术失败的主要原因。丝裂霉素C和5-氟尿嘧啶毒性太大,不能用于眼内。新发现:肾上腺素降低了小梁网细胞的收缩性,抑制了关键细胞周期基因和纤维化基因的表达,且无显著细胞毒性。前房内注射0.05%肾上腺素在MIGS患者中未导致任何眼部或全身不良反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3791/11868348/e04e0b97771d/417_2024_6642_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3791/11868348/d62a3a611b13/417_2024_6642_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3791/11868348/648e0844566d/417_2024_6642_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3791/11868348/e03ce38ba3a2/417_2024_6642_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3791/11868348/e04e0b97771d/417_2024_6642_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3791/11868348/d62a3a611b13/417_2024_6642_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3791/11868348/648e0844566d/417_2024_6642_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3791/11868348/e03ce38ba3a2/417_2024_6642_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3791/11868348/e04e0b97771d/417_2024_6642_Fig4_HTML.jpg

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