Department of Ophthalmology, Carmel Medical Center, Haifa, 34362, Israel.
Graefes Arch Clin Exp Ophthalmol. 2011 Jul;249(7):1047-55. doi: 10.1007/s00417-011-1658-0. Epub 2011 Mar 31.
Glaucoma filtering surgery may be compromised by cystic blebs which develop more frequently when anti-metabolites are used to arrest wound healing. Matrix metalloproteinases (MMPs) and the naturally occurring tissue inhibitors of metalloproteinases (TIMPs) are essential in connective tissue remodeling and wound healing. This study aimed to determine whether filtering blebs display increased expression of MMP-2, MMP-9, TIMP-1 and TIMP-2, and whether it is reflected in tear fluid.
Tissue samples from leaking blebs (n = 5) and control conjunctiva (n = 5) were evaluated by immunohistochemistry for MMP-2, MMP-9, TIMP-1 and TIMP-2. Tear fluid was collected from 12 patients (12 eyes) with cystic blebs and ten patients (ten eyes) with flat blebs following trabeculectomy with Mitomycin C applied and 16 controls. MMP levels were evaluated by zymography and TIMP levels by Western blot analysis.
Conjunctival tissue was obtained from five eyes with cystic leaking blebs and five control eyes undergoing cataract surgery. More extensive MMP-2 and MMP-9 expression was found in the epithelial and stromal layers of blebs than in control conjunctiva. TIMP-1and TIMP-2 were expressed in all layers of the blebs, but only in the epithelium of control conjunctiva. MMP-2 and proMMP-2 activity in tears from eyes with flat blebs was significantly higher than that of controls, while activity in tears of eyes with cystic blebs was significantly higher than in those with flat blebs. There was no difference in MMP-9 activity between tears of control and post-filtering surgery eyes.
Increased MMPs and TIMPs expression is associated with the formation of filtering blebs, suggesting involvement of MMPs in bleb remodeling. MMP-2 and ProMMP-2 levels in tear fluid may be markers for bleb configuration.
抗代谢药物用于抑制伤口愈合时，更常发生囊泡性滤过泡，这可能会影响青光眼滤过性手术的效果。基质金属蛋白酶（MMPs）及其天然组织抑制剂（TIMPs）在连接组织重塑和伤口愈合中起着至关重要的作用。本研究旨在确定滤过泡是否表现出 MMP-2、MMP-9、TIMP-1 和 TIMP-2 表达增加，以及这种增加是否反映在泪液中。
通过免疫组织化学方法评估 5 例渗漏性囊泡（n=5）和 5 例对照性结膜（n=5）组织中的 MMP-2、MMP-9、TIMP-1 和 TIMP-2。在应用丝裂霉素 C 进行小梁切除术并伴有囊性滤过泡的 12 例患者（12 只眼）和伴有扁平滤过泡的 10 例患者（10 只眼）中收集泪液。通过酶谱法评估 MMP 水平，通过 Western blot 分析评估 TIMP 水平。
从 5 只具有囊性渗漏性囊泡的眼睛和 5 只接受白内障手术的对照性眼睛中获得了结膜组织。囊泡的上皮和基质层中 MMP-2 和 MMP-9 的表达比对照性结膜更广泛。TIMP-1 和 TIMP-2 在囊泡的所有层中表达，但仅在对照性结膜的上皮层中表达。具有扁平滤过泡的眼睛的泪液中的 MMP-2 和 proMMP-2 活性明显高于对照组，而具有囊性滤过泡的眼睛的泪液中的活性明显高于具有扁平滤过泡的眼睛。泪液中 MMP-9 的活性在对照组和滤过术后眼睛之间没有差异。
MMPs 和 TIMPs 的表达增加与滤过泡的形成有关，提示 MMPs 参与了滤过泡的重塑。泪液中的 MMP-2 和 ProMMP-2 水平可能是滤过泡结构的标志物。
