Purchase this article with an account.
Hagen Thieme, Jens Uwe Nass, Michael Nuskovski, Nikolaos E. Bechrakis, Friederike Stumpff, Olaf Strauss, Michael Wiederholt; The Effects of Protein Kinase C on Trabecular Meshwork and Ciliary Muscle Contractility. Invest. Ophthalmol. Vis. Sci. 1999;40(13):3254-3261.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
purpose. The possible role of protein kinase C (PKC) inhibitors in novel
pressure-lowering drugs is currently under investigation. To gain
further insight into regulation of contractility by PKC in trabecular
meshwork (TM) and ciliary muscle (CM), the effects of various PKC
inhibitors and activators were tested.
methods. Isometric tension measurements of bovine TM and CM strips were
performed. PKC was stimulated by phorbol ester and by the
diacylglycerol analogue diC8. PKC blockade was accomplished
using H7 and myristoilated PKC substrate (mPKC). Western blot analysis
was used to identify specific PKC isoforms in human trabecular meshwork
(HTM), human ciliary muscle (HCM), and bovine TM and CM.
results. In tissues precontracted by carbachol PKC antagonist H7 led to a
relaxation of TM (25 ± 7.2 versus 100%; n = 8) with no effect on CM. mPKC substrate selectively blocks PKC. This
substance led to relaxation of TM (32.8 ± 7.4 versus 100%, n = 7), whereas CM was not affected. PMA at
concentrations of 10−6 M led to a slow contraction of both
tissues that was more marked in TM. DiC8 and 4α-phorbol
had no effect on contractility. Western blot analysis revealed
expression of calcium-dependent PKC-α and calcium-independent PKC-ε
isoforms in HTM and HCM. PKC-ε expression was more pronounced in HTM
than in HCM. Similar PKC isoform expression was found in native bovine
conclusions. PKC isoforms show different tissue distributions in human and bovine TM
and CM. Contractility differences exist in both tissues in response to
PKC antagonists and agonists. The data indicate that PKC may be
involved in regulation of aqueous humor outflow by the TM. Thus,
inhibition of PKC may represent a new way of influencing outflow
facility through isolated relaxation of TM.
This PDF is available to Subscribers Only