Role of tumour necrosis factor-α (TNFα) in the functional properties of hyalocytes

Background/aim Tumour necrosis factor-α (TNFα) is an inflammatory cytokine that is upregulated in various vitreoretinal diseases including uveitis and diabetic retinopathy. Recently, our studies have indicated that hyalocytes contribute to the pathogenesis of these diseases. However, the impact of TNFα on the functional properties of hyalocytes is unknown. Methods Hyalocytes were isolated from bovine eyes. Cellular proliferation, migration and gel contraction in response to TNFα and the other inflammatory cytokines were analysed by thymidine uptake, Boyden's chamber assay and collagen gel contraction assay, respectively. Furthermore, we estimated the effect of dexamethasone on these properties of hyalocytes. Results TNFα promoted proliferation, migration and gel contraction by hyalocytes. Dexamethasone inhibited TNFα-induced proliferation but not migration. Dexamethasone did not inhibit TNFα-induced gel contraction but further increased contraction. Furthermore, dexamethasone inhibited TNFα-induced extracellular signal-related kinase (ERK)1/2 phosphorylation in hyalocytes. Conclusion This study indicates that TNFα in vitreous and retina causes activation of hyalocytes, and the activated hyalocytes contribute to the pathogenesis of inflammatory vitreoretinal diseases. Steroid treatment appears to inhibit the activation of hyalocytes in the early stages of the diseases, but might have adverse effects in the late stage through membrane contraction.

[1]  Y. Hata,et al.  Comprehensive Analysis of Inflammatory Immune Mediators in Vitreoretinal Diseases , 2009, PloS one.

[2]  L. Aiello,et al.  Possible contribution of hyalocytes to idiopathic epiretinal membrane formation and its contraction , 2009, British Journal of Ophthalmology.

[3]  A. Hafezi-Moghadam,et al.  Role of TGF-β in proliferative vitreoretinal diseases and ROCK as a therapeutic target , 2008, Proceedings of the National Academy of Sciences.

[4]  Y. Hata,et al.  Vascular endothelial growth factor expression by hyalocytes and its regulation by glucocorticoid , 2008, British Journal of Ophthalmology.

[5]  A. Hafezi-Moghadam,et al.  Potent Inhibition of Cicatricial Contraction in Proliferative Vitreoretinal Diseases by Statins , 2008, Diabetes.

[6]  Y. Hata,et al.  Transforming growth factor-beta2 and connective tissue growth factor in proliferative vitreoretinal diseases: possible involvement of hyalocytes and therapeutic potential of Rho kinase inhibitor. , 2007, Diabetes.

[7]  S. Sizmaz,et al.  Determination of vitreous interleukin-1 (IL-1) and tumour necrosis factor (TNF) levels in proliferative diabetic retinopathy , 2006, Eye.

[8]  A. Joussen,et al.  Inhibition of TNF-alpha reduces laser-induced choroidal neovascularization. , 2006, Experimental eye research.

[9]  Y. Hata,et al.  Critical role of the Rho-kinase pathway in TGF-beta2-dependent collagen gel contraction by retinal pigment epithelial cells. , 2006, Experimental eye research.

[10]  T. E. Hinds.  Diseases , 2021, Modeling Biological Systems.

[11]  Janet L. Davis,et al.  Vitrectomy in the treatment of uveitis. , 2005, American journal of ophthalmology.

[12]  T. Hisatomi,et al.  The characterisation of hyalocytes: the origin, phenotype, and turnover , 2005, British Journal of Ophthalmology.

[13]  Y. Hata,et al.  The involvement of the rho-kinase pathway and its regulation in cytokine-induced collagen gel contraction by hyalocytes. , 2004, Investigative ophthalmology & visual science.

[14]  Y. Hata,et al.  Functional properties of hyalocytes under PDGF-rich conditions. , 2004, Investigative ophthalmology & visual science.

[15]  S. Yoshida,et al.  Induction of IL-8, MCP-1, and bFGF by TNF-α in retinal glial cells: implications for retinal neovascularization during post-ischemic inflammation , 2004, Graefe's Archive for Clinical and Experimental Ophthalmology.

[16]  T. Sakamoto.  [Cell biology of hyalocytes]. , 2003, Nippon Ganka Gakkai zasshi.

[17]  Y. Hata,et al.  Possible Benefits of Triamcinolone-Assisted Pars Plana Vitrectomy for Retinal Diseases , 2003, Retina.

[18]  K. Sonoda,et al.  Pars plana vitrectomy assisted by triamcinolone acetonide for refractory uveitis: a case series study , 2003, The British journal of ophthalmology.

[19]  M. Kuwano,et al.  Synergistic Effect of TNF-α in Soluble VCAM-1-Induced Angiogenesis Through α4 Integrins1 , 2003, The Journal of Immunology.

[20]  M. Kuwano,et al.  Synergistic effect of TNF-alpha in soluble VCAM-1-induced angiogenesis through alpha 4 integrins. , 2003, Journal of immunology.

[21]  F. Grus,et al.  Detection of Vascular Endothelial Growth Factor and Tumor Necrosis Factor Alpha in Epiretinal Membranes of Proliferative Diabetic Retinopathy, Proliferative Vitreoretinopathy and Macular Pucker , 1998, Ophthalmologica.

[22]  J. C. André,et al.  Hyalocyte-like cells are more numerous in the posterior chamber than they are in the vitreous of the rabbit eye. , 1998, Experimental eye research.

[23]  H. Flynn,et al.  Vitrectomy for diabetic macular edema associated with a thickened and taut posterior hyaloid membrane. , 1996, American journal of ophthalmology.

[24]  N. Yoshimura,et al.  Tumor necrosis factor-α gene is expressed in stimulated retinal pigment epithelial cells in culture , 1992 .

[25]  N. Yoshimura,et al.  Tumor necrosis factor-alpha gene is expressed in stimulated retinal pigment epithelial cells in culture. , 1992, Biochemical and biophysical research communications.

[26]  A. Hamburg.  Some investigations on the cells of the vitreous body. , 1959, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde.