HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Wall, D. S. Articles by Paradis, H. Search for Related Content PubMed PubMed Citation Articles by Wall, D. S. Articles by Paradis, H.

Conditional Knockdown of Tubedown-1 in Endothelial Cells Leads to Neovascular Retinopathy

¹From the Division of Basic Medical Sciences, Department of Medicine, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada; and the ²Smith Kettlewell Eye Research Institute, San Francisco, California.

PURPOSE. Identification of novel proteins involved in retinal neovascularization may facilitate new and more effective molecular-based treatments for proliferative retinopathy. Tubedown-1 (Tbdn-1) is a novel protein that shows homology to the yeast acetyltransferase subunit NAT1 and copurifies with an acetyltransferase activity. Tbdn-1 is expressed in normal retinal endothelium but is specifically suppressed in retinal endothelial cells from patients with proliferative diabetic retinopathy. The purpose of this study was to investigate the importance of Tbdn-1 expression in retinal blood vessels in vivo.

METHODS. A bitransgenic mouse model that enables conditional knockdown of Tbdn-1 specifically in endothelial cells was produced and studied using molecular, histologic, and immunohistochemical techniques and morphometric analysis.

RESULTS. Tbdn-1–suppressed mice exhibited retinal and choroidal neovascularization with intra- and preretinal fibrovascular lesions similar to human proliferative retinopathies. Retinal lesions observed in Tbdn-1–suppressed mice increased in severity with prolonged suppression of Tbdn-1. In comparison to normal retina, the retinal lesions displayed alterations in the basement membrane of blood vessels and in the distribution of glial and myofibroblastic cells. Moreover, the pathologic consequences of Tbdn-1 knockdown in endothelium were restricted to the retina and the choroid.

CONCLUSIONS. These results indicate that the maintenance of Tbdn-1 expression is important for retinal blood vessel homeostasis and for controlling retinal neovascularization in adults. Restoration of Tbdn-1 protein expression and/or activity may provide a novel approach for treating proliferative retinopathies.

This article has been cited by other articles:

				H. Paradis, T. Islam, S. Tucker, L. Tao, S. Koubi, and R. L. Gendron Tubedown associates with cortactin and controls permeability of retinal endothelial cells to albumin J. Cell Sci., June 15, 2008; 121(12): 1965 - 1972. [Abstract] [Full Text] [PDF]

				A. Arora, G. J. McKay, and D. A. C. Simpson Prediction and Verification of miRNA Expression in Human and Rat Retinas Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 3962 - 3967. [Abstract] [Full Text] [PDF]

				D. T. Martin, R. L. Gendron, J. A. Jarzembowski, A. Perry, M. H. Collins, C. Pushpanathan, E. Miskiewicz, V. P. Castle, and H. Paradis Tubedown Expression Correlates with the Differentiation Status and Aggressiveness of Neuroblastic Tumors Clin. Cancer Res., March 1, 2007; 13(5): 1480 - 1487. [Abstract] [Full Text] [PDF]

				A. K.H. Cheung, M. K.L. Fung, A. C.Y. Lo, T. T.L. Lam, K. F. So, S. S.M. Chung, and S. K. Chung Aldose Reductase Deficiency Prevents Diabetes-Induced Blood-Retinal Barrier Breakdown, Apoptosis, and Glial Reactivation in the Retina of db/db Mice Diabetes, November 1, 2005; 54(11): 3119 - 3125. [Abstract] [Full Text] [PDF]