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Functional Characteristics of Connective Tissue Growth Factor on Vitreoretinal Cells

From the Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Address correspondence and reprint requests to Yasuaki Hata, MD, PhD, Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. E-mail: hatachan{at}med.kyushu-u.ac.jp

Abbreviations: BAEC, bovine aortic endothelial cell; BREC, bovine retinal capillary endothelial cell; BRPE, bovine retinal pigment epithelial cell; CTGF, connective tissue growth factor; DMEM, Dulbecco's modified Eagle's medium; FBS, fetal bovine serum; HUVEC, human umbilical vein endothelial cell; MAPK, mitogen-activated protein kinase; PDR, proliferative diabetic retinopathy; PVR, proliferative vitreoretinopathy; REC, retinal capillary endothelial cell; RPE, retinal pigment epithelial cell; RRD, rhegmatogenous retinal detachment; TGF-ß, transforming growth factor-ß; VEGF, vascular endothelial growth factor

Connective tissue growth factor (CTGF) level is elevated in eyes with proliferative vitreoretinal diseases, such as proliferative diabetic retinopathy and proliferative vitreoretinopathy (PVR), as we previously reported, but its functional characteristics on vitreoretinal cells are yet to be clarified. In this study, we demonstrated a growth-promoting effect of CTGF on cultured hyalocytes and bovine retinal pigment epithelial cells (BRPEs) with the induction of p44/p42 mitogen-activated protein kinase phosphorylation and [³H]thymidine incorporation. CTGF also stimulated the synthesis of fibronectin by hyalocytes and BRPEs without significant effect on collagen gel contraction by these cells. On the other hand, CTGF had no direct effects on the proliferation, migration, or in vitro tube formation by vascular endothelial cells. Nevertheless, CTGF promoted vascular endothelial growth factor (VEGF) gene expression by hyalocytes and BRPEs. Although the concentrations of both CTGF and VEGF in the human vitreous samples with proliferative vitreoretinal diseases were elevated, there was no significant correlation between these concentrations. These findings indicate that CTGF appears to be involved in the formation of proliferative membranes without direct regulation of their cicatricial contraction in the pathogenesis of proliferative vitreoretinal diseases. Whereas CTGF might have no direct effects or minimal effects, if any, on retinal neovascularization, it is possible that CTGF has indirect effects by modulating the expression of VEGF.

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