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Editors Selection IGR 11-4

Basic research: TGF-β2 and optic nerve

Comment by James Lindsey on:

11757 Transforming growth factor-beta 2 modulated extracellular matrix component expression in cultured human optic nerve head astrocytes, Fuchshofer R; Birke M; Welge-Lussen U et al., Investigative Ophthalmology and Visual Science, 2005; 46: 568-578

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Transforming growth factor-Beta2 (TGF-β 2) is a dimeric peptide that can potently induce extracellular matrix remodeling in many different tissue types. Earlier studies found elevated TGF-β 2 in the aqueous humor and in optic nerve astrocytes of glaucomatous eyes. To further clarify the significance of these observations, Fuchshofer et al. (11) assessed the effect of adding TGF-b2 to human optic nerve head astrocyte cultures on the mRNA and protein expression of genes for several matrix components; as well as genes for connective tissue growth factor (CTGF), an upstream regulator of matrix component synthesis, and thrombospondin-1, an activator of TGF-β 2. Gene expression was evaluated by Northern blotting and RT-PCR. Protein expression was assessed by Western blotting. Results were quantified by image analysis or by imaging luminometry. They found TGF-β 2 increased both mRNA and protein expression of genes for subunits of collagens types 1 and 4, fibronectin, tissue transglutaminase (which facilitates matrix assembly), CTGF, and thrombospondin-1. Transfection of the cultures with CTGF silencer mRNA inhibited all of the above inductions by TGF-β 2 except that of thrombospondin-1. Hence, the authors concluded that TGF-β 2 facilitates extracellular matrix production by optic nerve head astrocytes. Moreover, this effect could depend upon the induction of CTGF expression. The experimental design appears to be sound and the images of the blots and gels were convincing. However, information regarding specificity of the antibodies and the number of times each experiment was repeated was missing. Also lacking was statistical evaluation of their quantitative results. Hence further investigations of these responses would be helpful. Nevertheless, these results underscore the potential importance of increased TGF-β 2 expression in glaucomatous optic nerve head matrix remodeling and suggest CTGF could be critically involved.

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