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Citations to this article

Lymphatic regulator PROX1 determines Schlemm’s canal integrity and identity
Dae-Young Park, … , Young-Kwon Hong, Gou Young Koh
Dae-Young Park, … , Young-Kwon Hong, Gou Young Koh
Published July 25, 2014
Citation Information: J Clin Invest. 2014;124(9):3960-3974. https://doi.org/10.1172/JCI75392.
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Research Article Article has an altmetric score of 18

Lymphatic regulator PROX1 determines Schlemm’s canal integrity and identity

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Abstract

Schlemm’s canal (SC) is a specialized vascular structure in the eye that functions to drain aqueous humor from the intraocular chamber into systemic circulation. Dysfunction of SC has been proposed to underlie increased aqueous humor outflow (AHO) resistance, which leads to elevated ocular pressure, a factor for glaucoma development in humans. Here, using lymphatic and blood vasculature reporter mice, we determined that SC, which originates from blood vessels during the postnatal period, acquires lymphatic identity through upregulation of prospero homeobox protein 1 (PROX1), the master regulator of lymphatic development. SC expressed lymphatic valve markers FOXC2 and integrin α9 and exhibited continuous vascular endothelial–cadherin (VE-cadherin) junctions and basement membrane, similar to collecting lymphatics. SC notably lacked luminal valves and expression of the lymphatic endothelial cell markers podoplanin and lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1). Using an ocular puncture model, we determined that reduced AHO altered the fate of SC both during development and under pathologic conditions; however, alteration of VEGF-C/VEGFR3 signaling did not modulate SC integrity and identity. Intriguingly, PROX1 expression levels linearly correlated with SC functionality. For example, PROX1 expression was reduced or undetectable under pathogenic conditions and in deteriorated SCs. Collectively, our data indicate that PROX1 is an accurate and reliable biosensor of SC integrity and identity.

Authors

Dae-Young Park, Junyeop Lee, Intae Park, Dongwon Choi, Sunju Lee, Sukhyun Song, Yoonha Hwang, Ki Yong Hong, Yoshikazu Nakaoka, Taija Makinen, Pilhan Kim, Kari Alitalo, Young-Kwon Hong, Gou Young Koh

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2010 Total
Citations: 4 12 5 9 13 14 4 5 16 10 6 3 1 102
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Citations to this article in year 2020 (14)

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Organogenesis and Distribution of the Ocular Lymphatic Vessels in the Anterior Eye: Implication to Glaucoma Surgery Site Selection
Yifan Wu, Young Jin Seong, Kin W. Li, Dongwon Choi, Eunkyung Park, George H. Daghlian, Eunson Jung, Khoa D. Bui, Luping Zhao, Shrimika Madhavan, Saren Daghlian, Patill Daghlian, Desmond Chin, Cho Il-Taeg, Alex Wong, Martin Heur, Sandy Zhang-Nunes, James C Tan, Masatsugu Ema, Tina T. Wong, Alex Huang, Young-Kwon Hong
JCI Insight 2020
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The Lymphatic Vasculature in the 21st Century: Novel Functional Roles in Homeostasis and Disease
G Oliver, J Kipnis, GJ Randolph, NL Harvey
Cell 2020
Ras Pathways on Prox1 and Lymphangiogenesis: Insights for Therapeutics
K Bui, YK Hong
Frontiers in Cardiovascular Medicine 2020
Eye lymphatic defects induced by bone morphogenetic protein 9 deficiency have no functional consequences on intraocular pressure
M Subileau, N Acar, A Carret, L Bretillon, I Vilgrain, S Bailly, D Vittet
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Absence of lymphatic vessels in term placenta
J Becker, GE Tchangou, S Schmidt, C Zelent, F Kahl, J Wilting
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Investigative ophthalmology & visual science 2020
Epigenetic regulation of the lineage specificity of primary human dermal lymphatic and blood vascular endothelial cells
C Tacconi, Y He, L Ducoli, M Detmar
Angiogenesis 2020
TGF-beta and TNF-alpha cooperatively induce mesenchymal transition of lymphatic endothelial cells via activation of Activin signals
Y Yoshimatsu, S Kimuro, J Pauty, K Takagaki, S Nomiyama, A Inagawa, K Maeda, KA Podyma-Inoue, K Kajiya, YT Matsunaga, T Watabe, N Takakura
PloS one 2020
A Small Molecule Inhibitor of VE-PTP Activates Tie2 in Schlemm's Canal Increasing Outflow Facility and Reducing Intraocular Pressure
G Li, AF Nottebaum, M Brigell, ID Navarro, U Ipe, S Mishra, M Gomez-Caraballo, H Schmitt, B Soldo, S Pakola, B Withers, KG Peters, D Vestweber, WD Stamer
Investigative ophthalmology & visual science 2020
A bioengineering approach to Schlemm's canal-like stem cell differentiation for in vitro glaucoma drug screening
YI Tian, X Zhang, K Torrejon, J Danias, S Gindina, A Nayyar, Y Du, Y Xie
Acta Biomaterialia 2020
Minimally Invasive Glaucoma Surgery: What Do We Know? Where Should We Go?
C Xin, H Wang, N Wang
Translational Vision Science & Technology 2020
Aqueous outflow regulation – 21st century concepts
M Johnstone, C Xin, J Tan, E Martin, J Wen, RK Wang
Progress in Retinal and Eye Research 2020
Effect of Electrical Stimulation of Cervical Sympathetic Ganglia on Intraocular Pressure Regulation According to Different Circadian Rhythms in Rats
Luo Z, Li M, Ye M, Ji P, Lou X, Huang J, Yao K, Zhao Y, Zhang H
Investigative ophthalmology & visual science 2020

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