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3',4'-二羟基黄酮醇抑制兔青光眼滤过手术模型中的纤维化反应。

3',4'-Dihydroxyflavonol Inhibits Fibrotic Response in a Rabbit Model of Glaucoma Filtration Surgery.

机构信息

Ophthalmology, Department of Surgery, University of Melbourne, Fitzroy, VIC 3065, Australia.

Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC 3002, Australia.

出版信息

Int J Mol Sci. 2024 Oct 7;25(19):10767. doi: 10.3390/ijms251910767.

Abstract

Post-operative fibrosis of the filtering bleb limits the success of glaucoma filtration surgery (GFS). To minimise subconjunctival scarring following GFS, treatment with antimetabolites such as Mitomycin C (MMC) has become standard practice; however, their use is associated with considerable side effects. This study aimed to investigate the anti-scarring properties of 3',4'-dihydroxyflavonol (DiOHF). GFS was performed in New Zealand white rabbits who received eye drops of DiOHF three times daily and vehicle eye drops after surgery ( = 5) or a single intraoperative treatment of MMC ( = 5). Blebs were imaged immediately following surgery and on days 7, 15, 21, and 28 for clinical examination. On day 28, eyes were harvested to assess collagen deposition, expression of α-SMA, oxidative stress, angiogenesis, fibroblast activity, and inflammation in the conjunctiva/Tenon's layer. At 7 and 28 days post-GFS, MMC-treated blebs were more ischaemic than DiOHF- or vehicle-treated blebs. On day 28, DiOHF treatment significantly suppressed collagen accumulation, CD31 expression, Vimentin expression, and CD45 expression compared to the vehicle control. No difference was observed in 3-Nitrotyrosine or αSMA expression between treatment groups. Treatment with DiOHF reduced conjunctival scarring and angiogenesis in rabbits with GFS, which was comparable to MMC. DiOHF may be a safer and more effective wound-modulating agent than conventional antifibrotic therapy in GFS.

摘要

术后滤过泡纤维化限制了青光眼滤过手术(GFS)的成功。为了最大限度地减少 GFS 后结膜下瘢痕形成,抗代谢药物如丝裂霉素 C(MMC)的治疗已成为标准做法;然而,它们的使用与相当大的副作用有关。本研究旨在研究 3',4'-二羟基黄酮醇(DiOHF)的抗瘢痕特性。新西兰白兔接受 DiOHF 滴眼剂每日三次,手术后(n=5)或术中单次 MMC 治疗(n=5)滴用载体滴眼剂。手术后立即对滤过泡进行成像,并在第 7、15、21 和 28 天进行临床检查。第 28 天,收获眼球以评估结膜/Tenon 层中的胶原沉积、α-SMA 表达、氧化应激、血管生成、成纤维细胞活性和炎症。在 GFS 后 7 和 28 天,与 DiOHF 或载体处理的滤过泡相比,MMC 处理的滤过泡更缺血。在第 28 天,与载体对照组相比,DiOHF 处理显著抑制了胶原积累、CD31 表达、波形蛋白表达和 CD45 表达。治疗组之间的 3-硝基酪氨酸或αSMA 表达没有差异。与 MMC 相比,DiOHF 治疗可减少 GFS 兔的结膜瘢痕形成和血管生成。DiOHF 可能是一种比传统抗纤维化治疗更安全、更有效的 GFS 伤口调节剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0757/11476621/6b8a6df0367d/ijms-25-10767-g001.jpg

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