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Ocular Hypotensive Efficacy of Src-family Tyrosine Kinase Inhibitors via Different Cellular Actions From Rock Inhibitors

Ocular Hypotensive Efficacy of Src-family Tyrosine Kinase Inhibitors via Different Cellular Actions From Rock Inhibitors

Tomoko Kirihara, Atsushi Shimazaki, Masatsugu Nakamura, Nobuaki Miyawaki

Exp Eye Res. 2014 Feb;119:97-105.

PMID: 24321889

Abstract:

We investigated the effects of Src-family tyrosine kinase (SFK) inhibitors on intraocular pressure (IOP) and trabecular meshwork (TM) cells. The SFK inhibitors, PP2, PP1, and damnacanthal, significantly lowered IOP from baseline following intracameral injection in ocular normotensive rabbits, and PP2 decreased trans-epithelial electrical resistance (TEER) of TM cell layers in a dose-dependent manner ranging from 0.1 μM to 100 μM. The maximal efficacy of PP2 on TEER was a reduction to 71.7% relative to the vehicle-treated group at 100 μM. PP2 decreased the adhesion of TM cells to culture surfaces either uncoated with specific ECM proteins dose-dependently or coated with extracellular matrix proteins such as laminin I, fibronectin, collagen type I and basement membrane extraction. Tyrosine phosphorylation of focal adhesion kinase and p130(cas) was decreased by PP2. On the other hand, major changes in actin staining of TM cells were not able to be detected after PP2 treatment, although quantitative analysis showed that PP2 induced some morphological changes which were in the different direction to those caused by Y-27632, a Rock inhibitor. Y-27632 at 10 μM increased the permeability of TM cell layers, but did not induce changes in the adhesion of TM cells. These results suggest that SFK inhibitors lower IOP, at least partly, by acting on TM cells in a manner that is distinct from Rock inhibitors.

Chemicals Related in the Paper:

Catalog Number	Product Name	CAS Number	Price
AP146986507	Y-27632 - CAS 146986-50-7	146986-50-7	Price
AP172889279	PP2 - CAS 172889-27-9	172889-27-9	Price
AP179248590-B	Src Kinase Inhibitor I - CAS 179248-59-0	179248-59-0	Price
AP4506665-B	Focal Adhesion Kinase Inhibitor I - CAS 4506-66-5	4506-66-5	Price
AP477849	Damnacanthal - CAS 477-84-9	477-84-9	Price

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