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Novel characterization and live imaging of Schlemm's canal expressing Prox-1.

Truong TN, Li H, Hong YK, Chen L - PLoS ONE (2014)

Bottom Line: 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.This may lead to new avenues toward the development of novel therapeutic intervention for relevant diseases, most notably glaucoma.

View Article: PubMed Central - PubMed

Affiliation: Graduate Group in Vision Science, University of California, Berkeley, California, United States of America; Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, California, United States of America.

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.

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Related in: MedlinePlus

Ultrastructure electron micrographs of Schelmm's canal in Prox-1 GFP mice.(A) Representative image showing normal morphology of Schlemm's canal (SC) and nearby trabecular meshwork (TM) in adult mice. (B) Magnified left boxed region in (A) of TM with characteristic intertrabecular spaces (asterisks). (C) Magnified right boxed region in (A) showing outer wall of Schlemm's canal lined with endothelial cells (arrow). A typical giant vacuole (arrowhead) was observed on the inner wall of Schlemm's canal. Scale bars, 4 µm (A); 2 µm (B, C).
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pone-0098245-g003: Ultrastructure electron micrographs of Schelmm's canal in Prox-1 GFP mice.(A) Representative image showing normal morphology of Schlemm's canal (SC) and nearby trabecular meshwork (TM) in adult mice. (B) Magnified left boxed region in (A) of TM with characteristic intertrabecular spaces (asterisks). (C) Magnified right boxed region in (A) showing outer wall of Schlemm's canal lined with endothelial cells (arrow). A typical giant vacuole (arrowhead) was observed on the inner wall of Schlemm's canal. Scale bars, 4 µm (A); 2 µm (B, C).

Mentions: It has been shown that the Prox-1-GFP mice faithfully recapitulate the expression pattern of Prox-1 in cells and structures without causing morphological change [15]. This is also confirmed by our electron microscopic examination of the Prox-1-GFP mice where normal and typical morphology of Schlemm's canal and trabecular meshwork was observed, as shown in Figure 3. While the outer wall of Schlemm's canal was lined with a monolayer of endothelial cells, typical giant vacuoles were seen on the inner wall protruding from the trabecular meshwork where characteristic intertrabecular spaces were observed.


Novel characterization and live imaging of Schlemm's canal expressing Prox-1.

Truong TN, Li H, Hong YK, Chen L - PLoS ONE (2014)

Ultrastructure electron micrographs of Schelmm's canal in Prox-1 GFP mice.(A) Representative image showing normal morphology of Schlemm's canal (SC) and nearby trabecular meshwork (TM) in adult mice. (B) Magnified left boxed region in (A) of TM with characteristic intertrabecular spaces (asterisks). (C) Magnified right boxed region in (A) showing outer wall of Schlemm's canal lined with endothelial cells (arrow). A typical giant vacuole (arrowhead) was observed on the inner wall of Schlemm's canal. Scale bars, 4 µm (A); 2 µm (B, C).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4020937&req=5

pone-0098245-g003: Ultrastructure electron micrographs of Schelmm's canal in Prox-1 GFP mice.(A) Representative image showing normal morphology of Schlemm's canal (SC) and nearby trabecular meshwork (TM) in adult mice. (B) Magnified left boxed region in (A) of TM with characteristic intertrabecular spaces (asterisks). (C) Magnified right boxed region in (A) showing outer wall of Schlemm's canal lined with endothelial cells (arrow). A typical giant vacuole (arrowhead) was observed on the inner wall of Schlemm's canal. Scale bars, 4 µm (A); 2 µm (B, C).
Mentions: It has been shown that the Prox-1-GFP mice faithfully recapitulate the expression pattern of Prox-1 in cells and structures without causing morphological change [15]. This is also confirmed by our electron microscopic examination of the Prox-1-GFP mice where normal and typical morphology of Schlemm's canal and trabecular meshwork was observed, as shown in Figure 3. While the outer wall of Schlemm's canal was lined with a monolayer of endothelial cells, typical giant vacuoles were seen on the inner wall protruding from the trabecular meshwork where characteristic intertrabecular spaces were observed.

Bottom Line: 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.This may lead to new avenues toward the development of novel therapeutic intervention for relevant diseases, most notably glaucoma.

View Article: PubMed Central - PubMed

Affiliation: Graduate Group in Vision Science, University of California, Berkeley, California, United States of America; Center for Eye Disease and Development, Program in Vision Science and School of Optometry, University of California, Berkeley, California, United States of America.

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.

Show MeSH
Related in: MedlinePlus