Novel Characterization and Live Imaging of Schlemm's Canal Expressing Prox-1

Schlemm's canal is an important structure of the conventional aqueous humor outflow pathway and is critically involved in regulating the intraocular pressure. In this study, we report a novel finding that prospero homeobox protein 1 (Prox-1), the master control gene for lymphatic development, is expressed in Schlemm's canal. Moreover, we provide a novel in vivo method of visualizing Schlemm's canal using a transgenic mouse model of Prox-1-green fluorescent protein (GFP). The anatomical location of Prox-1+ Schlemm's canal was further confirmed by in vivo gonioscopic examination and ex vivo immunohistochemical analysis. Additionally, we show that the Schlemm's canal is distinguishable from typical lymphatic vessels by lack of lymphatic vessel endothelial hyaluronan receptor (LYVE-1) expression and absence of apparent sprouting reaction when inflammatory lymphangiogenesis occurred in the cornea. Taken together, our findings offer new insights into Schlemm's canal and provide a new experimental model for live imaging of this critical structure to help further our understanding of the aqueous humor outflow. This may lead to new avenues toward the development of novel therapeutic intervention for relevant diseases, most notably glaucoma.

施莱姆管（Schlemm's canal）是房水常规流出通路的重要结构，在眼压调控中发挥关键作用。本研究首次报道了一项全新发现：淋巴发育主控基因prospero同源盒蛋白1（Prox-1）可在施莱姆管中表达。此外，本研究建立了一种全新的活体可视化施莱姆管的方法，即利用Prox-1-绿色荧光蛋白（GFP）转基因小鼠模型。通过活体前房角镜检查与离体免疫组织化学分析，本研究进一步验证了Prox-1阳性施莱姆管的解剖定位。本研究还发现，施莱姆管可通过两项特征与典型淋巴管区分：其一不表达淋巴管内皮透明质酸受体（LYVE-1），其二当角膜发生炎症性淋巴管生成时，施莱姆管无明显出芽反应。综上，本研究为施莱姆管的相关研究提供了新的认知，并为该关键结构的活体成像提供了全新的实验模型，有助于进一步阐明房水流出机制，或可为相关疾病（尤其是青光眼）的新型治疗干预手段开发开辟新路径。