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Gene transfer of soluble TGF-β type II receptor inhibits experimental proliferative vitreoretinopathy

Abstract

This study was conducted to investigate a method of gene therapy for proliferative vitreoretinopathy (PVR) by inhibiting type β transforming growth factor (TGF-β). PVR was induced in pigmented rabbits by intravitreal injection of 50 000 rabbit conjunctival fibroblasts after vitrectomy. Subsequently, the eyes received an intravitreal application of adenovirus vector encoding a soluble type II TGF-β receptor (AdTβ-ExR, n = 10) or adenoviral vector expressing β-galactosidase (AdLacZ) (n = 10) or balanced salt solution (BSS) (n = 6). The eyes were examined ophthalmoscopically for 28 days after surgery, and the clinical stage of PVR was evaluated on a scale of zero to five. Histological examinations were performed on the treated eyes on day 28. All control eyes injected with AdLacZ or BSS developed PVR, characterized by retinal detachment and the formation of intravitreal membranes within 7 days. The eyes injected with AdTβ-ExR also developed features of PVR, but the average severity from day 5 to day 28 was significant lower than in the control eyes (P < 0.05). TGF-β plays an important role in PVR progression in a PVR model, and prevention of TGF-β signaling could be therapeutically useful.

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Acknowledgements

This work is supported in part by Grants-in-Aid No. 11002994 from the Scientific Research Department of the Ministry of Education, Science, Culture and Sports of the Japanese Government, the Japan Society for the Promotion of Science (Tokyo), and the Japan Eye Bank Association (Tokyo). The authors thank Dr Kenneth W Parker for editorial assistance.

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Oshima, Y., Sakamoto, T., Hisatomi, T. et al. Gene transfer of soluble TGF-β type II receptor inhibits experimental proliferative vitreoretinopathy. Gene Ther 9, 1214–1220 (2002). https://doi.org/10.1038/sj.gt.3301789

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