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