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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ikuno, Y. Articles by Kazlauskas, A. Search for Related Content PubMed PubMed Citation Articles by Ikuno, Y. Articles by Kazlauskas, A.

An In Vivo Gene Therapy Approach for Experimental Proliferative Vitreoretinopathy Using the Truncated Platelet-Derived Growth Factor Receptor

From the Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts.

PURPOSE. Proliferative vitreoretinopathy (PVR) is a serious problem in vitreoretinal surgeries. A report of a previous study has indicated that platelet-derived growth factor receptor (PDGFR) plays an important role in a rabbit model of this disease and that a dominant negative PDGFR potently suppresses PVR in an ex vivo setting. Herein, the effect of in vivo gene delivery of a dominant negative PDGFR on PVR was tested in a rabbit model of the disease.

METHODS. The dominant negative PDGFR (TR) is a truncated version of the receptor, which does not have the intracellular domain. It was expressed by using a retrovirus. In vitro characterization of TR was performed in primary cultures of rabbit conjunctival fibroblasts (RCFs). Western blot analysis was used to check the expression of TR protein. A type I collagen gel contraction assay was performed to test the efficacy of TR on PDGF-dependent cellular responses in vitro. The in vivo efficacy and specificity of the retrovirus was determined by injecting a green fluorescent protein (GFP) retrovirus into rabbits that had been preinjected with RCFs. The impact of the TR retrovirus on PVR was tested by using the rabbit model in which PVR was induced by the injection of RCFs and platelet-rich plasma (PRP).

RESULTS. TR was expressed at more that 50 times the level of endogenous PDGFR in RCFs and severely reduced PDGF-dependent contraction of collagen gels. Intravitreal injection of the GFP retrovirus resulted in expression of GFP primarily in the injected RCFs. Whereas injection of RCFs induced complete retinal detachment in 100% of the animals, co-injection of the TR retrovirus substantially reduced the severity and incidence of retinal detachments.

CONCLUSIONS. Gene therapy with a retrovirus used to express a dominant negative PDGFR attenuates PVR in a rabbit model of the disease. This strategy may be a new approach to preventing PVR in humans.

This article has been cited by other articles:

				S. Saika, O. Yamanaka, I. Nishikawa-Ishida, A. Kitano, K. C. Flanders, Y. Okada, Y. Ohnishi, Y. Nakajima, and K. Ikeda Effect of Smad7 Gene Overexpression on Transforming Growth Factor beta-Induced Retinal Pigment Fibrosis in a Proliferative Vitreoretinopathy Mouse Model Arch Ophthalmol, May 1, 2007; 125(5): 647 - 654. [Abstract] [Full Text] [PDF]

				H.-J. Chen and Z.-Z. Ma N-Cadherin Expression in a Rat Model of Retinal Detachment and Reattachment Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1832 - 1838. [Abstract] [Full Text] [PDF]

				R. N. Kumar, J. H. Ha, R. Radhakrishnan, and D. N. Dhanasekaran Transactivation of Platelet-Derived Growth Factor Receptor {alpha} by the GTPase-Deficient Activated Mutant of G{alpha}12 Mol. Cell. Biol., January 1, 2006; 26(1): 50 - 62. [Abstract] [Full Text] [PDF]

				K. Hirayama, Y. Hata, Y. Noda, M. Miura, I. Yamanaka, H. Shimokawa, and T. Ishibashi The Involvement of the Rho-Kinase Pathway and Its Regulation in Cytokine-Induced Collagen Gel Contraction by Hyalocytes Invest. Ophthalmol. Vis. Sci., November 1, 2004; 45(11): 3896 - 3903. [Abstract] [Full Text] [PDF]

				Y. Zheng, H. Bando, Y. Ikuno, Y. Oshima, M. Sawa, M. Ohji, and Y. Tano Involvement of Rho-Kinase Pathway in Contractile Activity of Rabbit RPE Cells In Vivo and In Vitro Invest. Ophthalmol. Vis. Sci., February 1, 2004; 45(2): 668 - 674. [Abstract] [Full Text] [PDF]

				R. V. Hoch and P. Soriano Roles of PDGF in animal development Development, October 15, 2003; 130(20): 4769 - 4784. [Abstract] [Full Text] [PDF]

				Y. Saishin, Y. Saishin, K. Takahashi, M.-S. Seo, M. Melia, and P. A. Campochiaro The Kinase Inhibitor PKC412 Suppresses Epiretinal Membrane Formation and Retinal Detachment in Mice with Proliferative Retinopathies Invest. Ophthalmol. Vis. Sci., August 1, 2003; 44(8): 3656 - 3662. [Abstract] [Full Text] [PDF]