Doheny Eye Institute and Department of Ophthalmology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Department of Surgery, Department of Biochemistry and Molecular Biology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Sci Rep. 2017 Dec 6;7(1):17071. doi: 10.1038/s41598-017-16897-y.
Outflow resistance in the aqueous drainage tract distal to trabecular meshwork is potentially an important determinant of intraocular pressure and success of trabecular bypass glaucoma surgeries. It is unclear how distal resistance is modulated. We sought to establish: (a) multimodal 2-photon deep tissue imaging and 3-dimensional analysis of the distal aqueous drainage tract (DT) in transgenic mice in vivo and ex vivo; (b) criteria for distinguishing the DT from blood and lymphatic vessels; and (c) presence of a DT wall organization capable of contractility. DT lumen appeared as scleral collagen second harmonic generation signal voids that could be traced back to Schlemm's canal. DT endothelium was Prox1-positive, CD31-positive and LYVE-1-negative, bearing a different molecular signature from blood and true lymphatic vessels. DT walls showed prominent filamentous actin (F-actin) labeling reflecting cells in a contracted state. F-actin co-localized with mesenchymal smooth muscle epitopes of alpha-smooth muscle actin, caldesmon and calponin, which localized adjacent and external to the endothelium. Our findings support a DT wall organization resembling that of blood vessels. This reflects a capacity to contract and support dynamic alteration of DT caliber and resistance analogous to the role of blood vessel tone in regulating blood flow.
房水流出道在巩膜突后的阻力可能是眼内压和小梁旁路青光眼手术成功的一个重要决定因素。目前尚不清楚如何调节远端阻力。我们试图建立：（a）多模式双光子深部组织成像和转基因小鼠在体和离体的远端房水引流道（DT）的三维分析；（b）区分 DT 与血管和淋巴管的标准；和（c）存在具有收缩能力的 DT 壁组织。DT 管腔呈现巩膜胶原二次谐波信号缺失，可以追踪到施莱姆管。DT 内皮细胞为 Prox1 阳性、CD31 阳性和 LYVE-1 阴性，与血液和真正的淋巴管具有不同的分子特征。DT 壁显示出明显的丝状肌动蛋白（F-actin）标记，反映了处于收缩状态的细胞。F-actin 与平滑肌肌动蛋白、钙调蛋白和钙调蛋白的间充质平滑肌表位共定位，定位于内皮细胞的相邻和外部。我们的发现支持类似于血管的 DT 壁组织。这反映了收缩的能力，并支持 DT 口径和阻力的动态变化，类似于血管张力在调节血流中的作用。
