Abstract
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.
Highlights
Schlemm’s canal is a circumferential channel located at the iridocorneal angle in the ocular anterior chamber
We found that the highly recognizable prospero-related homeobox 1 (Prox-1)+ Schlemm’s canal was distinguishable from typical lymphatic vessels by lack of lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1) expression and absence of apparent sprouting reaction when inflammatory lymphangiogenesis was induced from limbal lymphatics
The Prox1-green fluorescent protein (GFP) BAC construct was created by inserting the GFP-coding sequences under the Prox-1 promoter in a Prox-1harboring BAC through homologous recombination by the GENSAT researchers [17]. This BAC contains a mouse genomic contig harboring all regulatory elements for Prox-1 expression and it has been shown that the Prox-1-GFP mice faithfully recapitulate Prox-1 expression in lymphatic vessels with no morphologic alternation [15]
Summary
Schlemm’s canal is a circumferential channel located at the iridocorneal angle in the ocular anterior chamber. It is part of the conventional aqueous humor outflow system of the anterior chamber, which accounts for 70–90% of the total aqueous humor that drains out of the eye. The endothelial cell lining of Schlemm’s canal is one of the primary sites of resistance to aqueous humor drainage and is a major determinant of intraocular pressure [1]. The particular contribution and exact mechanisms by which this continuous endothelium monolayer of Schlemm’s canal resists aqueous humor outflow still remain largely unclear in both normal and glaucomatous eyes. It is essential to enhance our knowledge on this important structure, which is a crucial prerequisite for developing new therapeutic strategies
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