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Segmental differences found in aqueous angiographic-determined high - and low-flow regions of human trabecular meshwork.
Experimental Eye Research ( IF 3.0 ) Pub Date : 2020-05-18 , DOI: 10.1016/j.exer.2020.108064
Sindhu Saraswathy 1 , Thania Bogarin 1 , Ernesto Barron 1 , Brian A Francis 1 , James C H Tan 1 , Robert N Weinreb 2 , Alex S Huang 1
Affiliation  

This work sought to compare aqueous angiographic segmental patterns with bead-based methods which directly visualize segmental trabecular meshwork (TM) tracer trapping. Additionally, segmental protein expression differences between aqueous angiographic-derived low- and high-outflow human TM regions were evaluated. Post-mortem human eyes (One Legacy and San Diego eye banks; n = 15) were perfused with fluorescent tracers (fluorescein [2.5%], indocyanine green [0.4%], and/or fluorescent microspheres). After angiographic imaging (Spectralis HRA+OCT; Heidelberg Engineering), peri-limbal low- and high-angiographic flow regions were marked. Aqueous angiographic segmental outflow patterns were similar to fluorescent microsphere TM trapping segmental patterns. TM was dissected from low- and high-flow areas and processed for immunofluorescence or Western blot and compared. Versican expression was relatively elevated in low-flow regions while MMP3 and collagen VI were relatively elevated in high-flow regions. TGF-β2, thrombospondin-1, TGF-β receptor1, and TGF-β downstream proteins such as α-smooth muscle actin were relatively elevated in low-flow regions. Additionally, fibronectin (FN) levels were unchanged, but the EDA isoform (FN-EDA) that is associated with fibrosis was relatively elevated in low-flow regions. These results show that segmental aqueous angiographic patterns are reflective of underlying TM molecular characteristics and demonstrate increased pro-fibrotic activation in low-flow regions. Thus, we provide evidence that aqueous angiography outflow visualization, the only tracer outflow imaging method available to clinicians, is in part representative of TM biology.

中文翻译:

在水性血管造影确定的人小梁网的高流量和低流量区域中发现了节段差异。

这项工作试图将水性血管造影的节段性图案与基于珠子的方法进行比较,该方法可直接可视化节段性小梁网(TM)示踪剂捕获。另外,评估了水性血管造影衍生的低流出和高流出人类TM区之间的节段蛋白表达差异。用荧光示踪剂(荧光素[2.5%],吲哚菁绿[0.4%]和/或荧光微球)灌注死后人眼(One Legacy和San Diego眼库; n = 15)。血管造影成像后(Spectralis HRA + OCT; Heidelberg Engineering),标出了沿肢体周围低和高血管造影的血流区域。血管造影分段流出模式类似于荧光微球TM捕获分段模式。从低流量和高流量区域解剖TM,并进行免疫荧光或蛋白质印迹处理并进行比较。Versican表达在低流量区域相对升高,而MMP3和胶原VI在高流量区域相对升高。在低流量区域,TGF-β2,血小板反应蛋白-1,TGF-β受体1和TGF-β下游蛋白(例如α-平滑肌肌动蛋白)相对升高。此外,纤连蛋白(FN)的水平不变,但与纤维化相关的EDA同工型(FN-EDA)在低流量区域相对升高。这些结果表明,节段性血管造影模式反映了潜在的TM分子特征,并证明在低流量区域中促纤维化激活增加。因此,我们提供了证据,即水性血管造影流出可视化,
更新日期:2020-05-18
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