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 (3) Citing Articles via Google Scholar Google Scholar Articles by Werdich, X. Q. Articles by Penn, J. S. Search for Related Content PubMed PubMed Citation Articles by Werdich, X. Q. Articles by Penn, J. S.

Specific Involvement of Src Family Kinase Activation in the Pathogenesis of Retinal Neovascularization

¹From the Departments of Cell and Developmental Biology and ²Ophthalmology and Visual Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee.

PURPOSE. Src family kinases (SFKs) are membrane-attached nonreceptor protein tyrosine kinases that link a variety of extracellular cues to intracellular signal pathways. The purpose of this study was to characterize the roles of SFKs in vascular endothelial growth factor (VEGF)–mediated retinal angiogenesis.

METHODS. Primary rat retinal glial Müller cells and bovine and human retinal microvascular endothelial cells (RMECs) were used in the in vitro studies. A rat model of retinopathy of prematurity (ROP) was used in the in vivo studies.

RESULTS. In vitro, SFKs were essential for hypoxia-induced VEGF expression in Müller cells and for VEGF signaling in RMECs. However, neither process required significant further phosphorylation of the SFK activation loop Tyr416. In vivo, in a rat model of ROP, a pronounced increase of retinal SFK Tyr416 phosphorylation was observed that was specifically associated with pathologic angiogenesis. These retinas also expressed significantly higher levels of VEGF than did those in healthy controls. Immunohistochemical analysis indicated that Müller cells were the major source of the elevated level of phospho-SFK Tyr416. Intravitreous injection of a selective SFK inhibitor, PP2, significantly reduced retinal VEGF and retinopathy in the ROP model, indicating that SFKs acted as important regulators in abnormal retinal angiogenesis.

CONCLUSIONS. Together, these data suggest that SFK activation through a Tyr416-dependent mechanism may be an important factor in the pathogenesis of retinal neovascularization.

This article has been cited by other articles:

				M. E. Hartnett, D. Martiniuk, G. Byfield, P. Geisen, G. Zeng, and V. L. Bautch Neutralizing VEGF Decreases Tortuosity and Alters Endothelial Cell Division Orientation in Arterioles and Veins in a Rat Model of ROP: Relevance to Plus Disease Invest. Ophthalmol. Vis. Sci., July 1, 2008; 49(7): 3107 - 3114. [Abstract] [Full Text] [PDF]

				Y. Saito, A. Uppal, G. Byfield, S. Budd, and M. E. Hartnett Activated NAD(P)H Oxidase from Supplemental Oxygen Induces Neovascularization Independent of VEGF in Retinopathy of Prematurity Model Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1591 - 1598. [Abstract] [Full Text] [PDF]