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Diabetes. 2007 Jan;56(1):231-8.

Transforming growth factor-beta2 and connective tissue growth factor in proliferative vitreoretinal diseases: possible involvement of hyalocytes and therapeutic potential of Rho kinase inhibitor.

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  • 1Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.


The critical association of connective tissue growth factor (CTGF), which is thought to be one of the downstream mediators of transforming growth factor-beta (TGF-beta), with vitreoretinal diseases remains to be clarified. In the current study, we first demonstrated the correlation between the concentrations of TGF-beta2 as well as CTGF in the vitreous and CTGF gene regulation in cultured hyalocytes. Concentrations of TGF-beta2 and CTGF in the vitreous from patients with proliferative vitreoretinal diseases were significantly higher than in those with nonproliferative diseases, and there was a positive correlation between their concentrations (r = 0.320, P < 0.01). Cultured hyalocytes expressed CTGF mRNA, which was enhanced in the presence of TGF-beta2, associated with nuclear accumulation of Smad4. TGF-beta2-dependent Smad4 translocation and CTGF gene expression were mediated through Rho kinase and at least partially via p38 mitogen-activated protein kinase. Finally, fasudil, a Rho kinase inhibitor already in clinical use, inhibited both Smad4 translocation and CTGF gene expression. In conclusion, combined effects of TGF-beta2 and CTGF appear to be involved in the pathogenesis of proliferative vitreoretinal diseases. Hyalocytes may be a possible source of CTGF and thus might play a role in vitreoretinal interface diseases. Furthermore, Rho kinase inhibitors might have therapeutic potential to control fibrotic disorders in the eye.

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