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T. Kita, Y. Hata, R. Arita, S. Kawahara, M. Miura, S. Nakao, Y. Mochizuki, A. Ueno, A. Hafezi-Moghadam, T. Ishibashi; Crucial Role of TGF-β2 in Proliferative Vitreoretinal Diseases and Rho-Kinase Pathway as a Therapeutic Target. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5172. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Cicatricial contraction of preretinal proliferative membrane causes severe vision loss by proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). Whereas transforming growth factor (TGF)-β has been reported to be overexpressed in the vitreous with those diseases and thought to be associated with the cellular contraction, its crucial role and intracellular signalings remain to be elucidated.
Human vitreous samples were collected from patients with various eye diseases and the concentrations of total and activated TGF-β2 were measured by enzyme-linked immunosorbent assay. Bovine hyalocytes were embedded in collagen gels and stimulated with the vitreous in the presence or absence of anti-TGF-β neutralizing antibody or Fasudil, a Rho-kinase inhibitor. In addition, the expression of α-smooth muscle actin (α-SMA) and the phosphorylation state of myosin light chain (MLC) were examined by Western blotting. The effects of Fasudil on the progression of experimental PVR in rabbit eyes and its safety were also investigated.
Vitreous samples with PDR and PVR significantly enhanced collagen gel contraction compared with those with non-proliferative diseases, and the degree of which was strongly correlated with the concentrations of activated TGF-β2. Vitreous samples with proliferative diseases also promoted α-SMA expression and MLC phosphorylation with significant suppressions by anti-TGF-β antibody, whereas Fasudil almost completely prohibited MLC phosphorylation without affecting α-SMA expression. Finally, Fasudil significantly inhibited the progression of PVR in rabbit eyes without any obvious toxicity to the retinal tissue.
TGF-β appears to play a crucial role in the cicatricial contraction in PDR and PVR among various factors in the vitreous, and Fasudil is possible to be a therapeutic agent for the prevention of the diseased state.
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