IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1167/iovs.08-2312 on March 25, 2009
 (Investigative Ophthalmology and Visual Science. 2009;50:4237-4243.)
© 2009 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.08-2312
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
iovs.08-2312v1
50/9/4237    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Ooi, Y. H.
Right arrow Articles by Rhee, D. J.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ooi, Y. H.
Right arrow Articles by Rhee, D. J.

Analysis of {alpha}2-adrenergic Receptors and Effect of Brimonidine on Matrix Metalloproteinases and Their Inhibitors in Human Ciliary Body

Yen Hoong Ooi, Dong-Jin Oh, and Douglas J. Rhee

From the Department of Ophthalmology, Massachusetts Eye and Ear Infirmary (MEEI), Boston, Massachusetts.

PURPOSE. To ascertain the expression pattern of {alpha}2-adrenergic receptors in the ciliary body (CB) and determine the effect of brimonidine on matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in ciliary body smooth muscle (CBSM) cells.

METHODS. Qualitative RT-PCR was performed to detect the mRNA of the {alpha}2-adrenergic receptor subtypes {alpha}2A, {alpha}2B, and {alpha}2C in CB and CBSM cultures. Immunohistochemistry and immunoblot analysis were performed to further investigate {alpha}2A receptor expression in CB tissue and CBSM cells. CBSM cells from 15 different human donors received control or brimonidine tartrate (45 nM) for 1, 3, or 7 days. Changes in pro-MMP-1, -2, -3, -9, and -24 and TIMP-1, -2, -3, and -4 levels were evaluated by Western blot, with GAPDH as the endogenous control. Zymography was used to assess the activity of MMP-1, -2, -3, and -9.

RESULTS. The mRNA of {alpha}2A, {alpha}2B, and {alpha}2C were detected in CB tissue and CBSM cells. Immunohistochemistry localized {alpha}2A receptors within the CB stroma. Immunoblot analysis demonstrated production by CBSM cells. Brimonidine increased pro-MMP-9 an average of 116% ± 34% (P = 0.0360); enzymatic activity of MMP-9 was unchanged. TIMP-4 decreased an average of 25% ± 8% (P = 0.0329) in conditioned medium, but increased 70% ± 13% (P = 0.0057) in cell lysates.

CONCLUSIONS. The presence of {alpha}2A, {alpha}2B, and {alpha}2C in CB tissue and CBSM cells indicates the possibility that brimonidine affects uveoscleral outflow. However, the changes in MMP-9 and TIMP-4 without significant changes in MMP-9 activity suggest that a role of the MMP/TIMP system in outflow is unlikely.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2009 by the Association for Research in Vision and Ophthalmology