| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
Published online before print April 10, 2008
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Article |
Production Promotes Apoptosis and the Loss of Retinal Microvascular Cells in Type 1 and Type 2 Models of Diabetic Retinopathy
,
From the Department of Periodontology and Oral Biology,* School of Dental Medicine, and Departments of Medicine and Ophthalmology, School of Medicine, Boston University, Boston, Massachusetts
@ To whom correspondence should be addressed. E-mail: dgraves{at}bu.edu.
 |
Abstract |
|---|
Retinal microvascular cell loss plays a critical role in the pathogenesis of diabetic retinopathy. To examine this further, type 1 streptozotocin-induced diabetic rats and type 2 Zucker diabetic fatty rats were treated by intravitreal injection of the tumor necrosis factor-specific inhibitor pegsunercept, and the impact was measured by analysis of retinal trypsin digests. For type 2 diabetic rats, the number of endothelial cells and pericytes positive for diabetes-enhanced activated caspase-3 decreased by 81% and 86%, respectively, when treated with pegsunercept (P < 0.05). Similarly, the number of diabetes-enhanced terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive endothelial cells and pericytes decreased by 81% and 67% respectively when treated with pegsunercept (P < 0.05). Diabetes-increased activated caspase-3- and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive microvascular cell numbers were both reduced by 81% and 80%, respectively, in pegsunercept-treated type 1 diabetic rats (P < 0.05). Inhibition of tumor necrosis factor reduced type 1 diabetes-enhanced pericyte ghost formation by 87% and the number of type 2 diabetes-enhanced pericyte ghosts by 62% (P < 0.05). Similarly, increased acellular capillary formation caused by type 1 and type 2 diabetes was reduced by 68% and 67%, respectively, when treated with pegsunercept (P < 0.05). These results demonstrate a previously unrecognized role of tumor necrosis factor-
in promoting the early pathogenesis of diabetic retinopathy leading to loss of retinal microvascular cells and demonstrate the potential therapeutic benefit of modulating its activity.
This article has been cited by other articles:
 |
|
 |
|
  S. Roy, K. Trudeau, S. Roy, Y. Behl, S. Dhar, and A. Chronopoulos New Insights into Hyperglycemia-induced Molecular Changes in Microvascular Cells Journal of Dental Research, February 1, 2010; 89(2): 116 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Behl, P. Krothapalli, T. Desta, S. Roy, and D. T. Graves FOXO1 Plays an Important Role in Enhanced Microvascular Cell Apoptosis and Microvascular Cell Loss in Type 1 and Type 2 Diabetic Rats Diabetes, April 1, 2009; 58(4): 917 - 925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ghosh, M. Khazaei, F. Moien-Afshari, L. S. Ang, D. J. Granville, C. B. Verchere, S. R. Dunn, P. McCue, A. Mizisin, K. Sharma, et al. Moderate exercise attenuates caspase-3 activity, oxidative stress, and inhibits progression of diabetic renal disease in db/db mice Am J Physiol Renal Physiol, April 1, 2009; 296(4): F700 - F708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Orasanu and J. Plutzky The pathologic continuum of diabetic vascular disease. J. Am. Coll. Cardiol., February 3, 2009; 53(5 Suppl): S35 - S42. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Arita, Y. Hata, S. Nakao, T. Kita, M. Miura, S. Kawahara, S. Zandi, L. Almulki, F. Tayyari, H. Shimokawa, et al. Rho Kinase Inhibition by Fasudil Ameliorates Diabetes-Induced Microvascular Damage Diabetes, January 1, 2009; 58(1): 215 - 226. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
