TY - JOUR
T1 - Visualization of conventional outflow tissue responses to netarsudil in living mouse eyes
AU - Li, Guorong
AU - Mukherjee, Dibyendu
AU - Navarro, Iris
AU - Ashpole, Nicole E.
AU - Sherwood, Joseph M.
AU - Chang, Jinlong
AU - Overby, Darryl R.
AU - Yuan, Fan
AU - Gonzalez, Pedro
AU - Kopczynski, Casey C.
AU - Farsiu, Sina
AU - Stamer, W. Daniel
N1 - Funding Information:
This work is supported in part by the BrightFocus Foundation ( G2015100 ) and that National Eye Institute ( EY005722 and EY019696 ). The authors thank Ying Hao from Duke Eye Center core facility for help with histology studies.
Publisher Copyright:
© 2016 The Authors
PY - 2016
Y1 - 2016
N2 - Visual impairment due to glaucoma currently impacts 70 million people worldwide. While disease progression can be slowed or stopped with effective lowering of intraocular pressure, current medical treatments are often inadequate. Fortunately, three new classes of therapeutics that target the diseased conventional outflow tissue responsible for ocular hypertension are in the final stages of human testing. The rho kinase inhibitors have proven particularly efficacious and additive to current therapies. Unfortunately, non-contact technology that monitors the health of outflow tissue and its response to conventional outflow therapy is not available clinically. Using optical coherence tomographic (OCT) imaging and novel segmentation software, we present the first demonstration of drug effects on conventional outflow tissues in living eyes. Topical netarsudil (formerly AR-13324), a rho kinase/ norepinephrine transporter inhibitor, affected both proximal (trabecular meshwork and Schlemm's Canal) and distal portions (intrascleral vessels) of the mouse conventional outflow tract. Hence, increased perfusion of outflow tissues was reliably resolved by OCT as widening of the trabecular meshwork and significant increases in cross-sectional area of Schlemm's canal following netarsudil treatment. These changes occurred in conjunction with increased outflow facility, increased speckle variance intensity of outflow vessels, increased tracer deposition in conventional outflow tissues and decreased intraocular pressure. This is the first report using live imaging to show real-time drug effects on conventional outflow tissues and specifically the mechanism of action of netarsudil in mouse eyes. Advancements here pave the way for development of a clinic-friendly OCT platform for monitoring glaucoma therapy.
AB - Visual impairment due to glaucoma currently impacts 70 million people worldwide. While disease progression can be slowed or stopped with effective lowering of intraocular pressure, current medical treatments are often inadequate. Fortunately, three new classes of therapeutics that target the diseased conventional outflow tissue responsible for ocular hypertension are in the final stages of human testing. The rho kinase inhibitors have proven particularly efficacious and additive to current therapies. Unfortunately, non-contact technology that monitors the health of outflow tissue and its response to conventional outflow therapy is not available clinically. Using optical coherence tomographic (OCT) imaging and novel segmentation software, we present the first demonstration of drug effects on conventional outflow tissues in living eyes. Topical netarsudil (formerly AR-13324), a rho kinase/ norepinephrine transporter inhibitor, affected both proximal (trabecular meshwork and Schlemm's Canal) and distal portions (intrascleral vessels) of the mouse conventional outflow tract. Hence, increased perfusion of outflow tissues was reliably resolved by OCT as widening of the trabecular meshwork and significant increases in cross-sectional area of Schlemm's canal following netarsudil treatment. These changes occurred in conjunction with increased outflow facility, increased speckle variance intensity of outflow vessels, increased tracer deposition in conventional outflow tissues and decreased intraocular pressure. This is the first report using live imaging to show real-time drug effects on conventional outflow tissues and specifically the mechanism of action of netarsudil in mouse eyes. Advancements here pave the way for development of a clinic-friendly OCT platform for monitoring glaucoma therapy.
KW - Conventional outflow
KW - Ocular hypertension
KW - Rho kinase inhibitor
KW - Schlemm's canal
KW - Trabecular meshwork
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U2 - 10.1016/j.ejphar.2016.04.002
DO - 10.1016/j.ejphar.2016.04.002
M3 - Article
C2 - 27085895
AN - SCOPUS:84964649332
VL - 787
SP - 20
EP - 31
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
ER -