| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1From the Department of Ophthalmology, Boston University School of Medicine, Boston, Massachusetts; the 2Department of Ophthalmology, Taipei Veterans General Hospital and National Yang-Ming University, Taipei, Taiwan; and 3Eye Research Laboratory, Shin-Yahashiradal Hospital, Chiba, Japan.
PURPOSE. To investigate the role of the gap junction protein, connexin-43 (Cx43) in the maintenance of retinal vascular homeostasis in diabetic retinopathy.
METHODS. In human retinal pericytes (HRPs) and bovine retinal pericytes (BRPs) grown for 7 days in normal (5 mM) or high (30 mM)-glucose medium, the Cx43 protein level was determined by Western blot analysis. Parallel experiments were performed in HRPs to determine the Cx43 mRNA level by RT-PCR, the distribution and localization of Cx43 protein by immunostaining, and gap junction intercellular communication (GJIC) activity by a scrape-loading dye transfer technique. Distribution and localization of Cx43 protein was also determined in pericyte–endothelial cell cocultures.
RESULTS. Western blot analysis of the Cx43 protein level in HRPs and BRPs indicated reduced Cx43 expression in the high-glucose condition (69.1% ± 17% of control, P = 0.004; 62.3% ± 19% of control, P = 0.001, respectively). The Cx43 mRNA level in HRPs grown in high-glucose medium also showed significant reduction (71.4% ± 16.8% of control, P = 0.02). The relative number of Cx43 plaques indicative of Cx43 localization at specific sites of contact between adjacent cells showed significant reduction in the high-glucose condition (61% ± 10% of control, P = 0.002); similarly, a significant reduction in the number of plaques was observed in cocultures grown in high-glucose medium compared with those in normal medium (59.4% ± 29% of control, P = 0.001). Cells with reduced Cx43 expression showed significantly reduced transfer of lucifer yellow (61% ± 13% of control, P = 0.001; r = 0.9).
CONCLUSIONS. High-glucose–induced downregulation of Cx43 expression and inhibition of GJIC in retinal pericytes may play a role in the disruption of vascular homeostasis in diabetic retinopathy.
This article has been cited by other articles:
|
|
 |
|
  C. E. Hills, R. Bland, D. C. Wheelans, J. Bennett, P. M. Ronco, and P. E. Squires Glucose-evoked alterations in connexin43-mediated cell-to-cell communication in human collecting duct: a possible role in diabetic nephropathy Am J Physiol Renal Physiol, November 1, 2006; 291(5): F1045 - F1051. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhang, X. Chen, D. Wu, W. Liu, J. Wang, Z. Feng, G. Cai, B. Fu, Q. Hong, and J. Du Downregulation of Connexin 43 Expression by High Glucose Induces Senescence in Glomerular Mesangial Cells J. Am. Soc. Nephrol., June 1, 2006; 17(6): 1532 - 1542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Chang, A. N. Dale, and K. H. Moley Maternal Diabetes Adversely Affects Preovulatory Oocyte Maturation, Development, and Granulosa Cell Apoptosis Endocrinology, May 1, 2005; 146(5): 2445 - 2453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. E. Walshe, G. Ferguson, P. Connell, C. O'Brien, and P. A. Cahill Pulsatile Flow Increases the Expression of eNOS, ET-1, and Prostacyclin in a Novel In Vitro Coculture Model of the Retinal Vasculature Invest. Ophthalmol. Vis. Sci., January 1, 2005; 46(1): 375 - 382. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kawamura, M. Kobayashi, Q. Li, S. Yamanishi, K. Katsumura, M. Minami, D. M Wu, and D. G Puro Effects of angiotensin II on the pericyte-containing microvasculature of the rat retina J. Physiol., December 15, 2004; 561(3): 671 - 683. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
