Mahale Alka, Fikri Fatma, Al Hati Khitam, Al Shahwan Sami, Al Jadaan Ibrahim, Al Katan Hind, Khandekar Rajiv, Maktabi Azza, Edward Deepak P
King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia.
Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, United States of America.
PLoS One. 2017 Nov 9;12(11):e0187506. doi: 10.1371/journal.pone.0187506. eCollection 2017.
Impervious encapsulation around Ahmed glaucoma valve (AGV) results in surgical failure raising intraocular pressure (IOP). Dysregulation of extracellular matrix (ECM) molecules and cellular factors might contribute to increased hydraulic resistance to aqueous drainage. Therefore, we examined these molecules in failed AGV capsular tissue. Immunostaining for ECM molecules (collagen I, collagen III, decorin, lumican, chondroitin sulfate, aggrecan and keratan sulfate) and cellular factors (αSMA and TGFβ) was performed on excised capsules from failed AGVs and control tenon's tissue. Staining intensity of ECM molecules was assessed using Image J. Cellular factors were assessed based on positive cell counts. Histopathologically two distinct layers were visible in capsules. The inner layer (proximal to the AGV) showed significant decrease in most ECM molecules compared to outer layer. Furthermore, collagen III (p = 0.004), decorin (p = 0.02), lumican (p = 0.01) and chondroitin sulfate (p = 0.02) was significantly less in inner layer compared to tenon's tissue. Outer layer labelling however was similar to control tenon's for most ECM molecules. Significantly increased cellular expression of αSMA (p = 0.02) and TGFβ (p = 0.008) was detected within capsular tissue compared to controls. Our results suggest profibrotic activity indicated by increased αSMA and TGFβ expression and decreased expression of proteoglycan (decorin and lumican) and glycosaminoglycans (chondroitin sulfate). Additionally, we observed decreased collagen III which might reflect increased myofibroblast contractility when coupled with increased TGFβ and αSMA expression. Together these events lead to tissue dysfunction potentially resulting in hydraulic resistance that may affect aqueous flow through the capsular wall.
艾哈迈德青光眼阀（AGV）周围形成的不透性包裹会导致手术失败，眼压（IOP）升高。细胞外基质（ECM）分子和细胞因子的失调可能会导致房水引流的液压阻力增加。因此，我们在失败的AGV囊膜组织中检测了这些分子。对取自失败的AGV的切除囊膜和对照Tenon组织进行了ECM分子（I型胶原、III型胶原、核心蛋白聚糖、纤连蛋白聚糖、硫酸软骨素、聚集蛋白聚糖和硫酸角质素）和细胞因子（α平滑肌肌动蛋白和转化生长因子β）的免疫染色。使用Image J评估ECM分子的染色强度。基于阳性细胞计数评估细胞因子。组织病理学上，囊膜中可见两个不同的层。与外层相比，内层（靠近AGV）的大多数ECM分子显著减少。此外，与Tenon组织相比，内层的III型胶原（p = 0.004）、核心蛋白聚糖（p = 0.02）、纤连蛋白聚糖（p = 0.01）和硫酸软骨素（p = 0.02）明显减少。然而，外层标记与对照Tenon组织的大多数ECM分子相似。与对照组相比，在囊膜组织中检测到α平滑肌肌动蛋白（p = 0.02）和转化生长因子β（p = 0.008）的细胞表达显著增加。我们的结果表明，α平滑肌肌动蛋白和转化生长因子β表达增加以及蛋白聚糖（核心蛋白聚糖和纤连蛋白聚糖）和糖胺聚糖（硫酸软骨素）表达减少表明存在促纤维化活性。此外，我们观察到III型胶原减少，当与转化生长因子β和α平滑肌肌动蛋白表达增加相结合时，这可能反映了肌成纤维细胞收缩性增加。这些事件共同导致组织功能障碍，可能导致液压阻力，从而影响房水通过囊膜壁的流动。
