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Editors Selection IGR 10-3

Basic research: TGF-b2 and optic nerve

Comment by Rosario Hernandez 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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In this well-conducted study, Fuchshofer et al. (11) analyzed the effects of TGF-β 2 on the synthesis of ECM, expression of connective tissue growth factor (CTGF) and on transglutaminase (TGM) and thrombospondin (TSP)-1, an activator of TGF-β 2. ONH astrocytes participate in the remodeling of the ECM in the lamina cribrosa in eyes with glaucoma. Members of the TGF-β family of growth factors are amongst the key regulators of ECM synthesis and degradation in the CNS during normal development and disease. TGF-β 2 is the predominant isoform expressed by astrocytes in the ONH in vivo and in vitro, thus this growth factor is a potential regulator of tissue remodeling in glaucoma. In this study cultured human ONH astrocytes were exposed to TGF-β 2 for 24 and 48h. TGF-β 2 increased expression of collagen type 1β 1 and type 4β 2, fibronectin and TSP whereas collagen type 3β 1 remained unchanged. CTGF expression was also induced by TGF-β 2.Transfection of siRNA to inhibit CTGF expression successfully suppressed expression of all ECM components except for TSP1. The data demonstrate that the ECM effects of TGF-β 2 on ONH astrocytes are mediated by CTGF in vitro. Their data also suggests that TSP1 activates TGF-β 2 and perhaps maintains TGF-β 2 in an active state by an autocrine mechanism. This study clearly supports a role for astrocytic TGF-β 2 in glaucomatous neuropathy by increasing synthesis of ECM creating an altered environment in the ONH. The authors draw a parallel between the role of TGF-β 2 in the trabecular meshwork and the ONH in glaucoma. Previous studies have shown expression of TGF binding proteins and members of the TGF-β signaling pathway in ONH astrocytes and in lamina cribrosa cells; this study provides the mechanism by which TGF-β 2 alters the microenvironment in the ONH. Moreover, important role of TGF-β in the CNS, and perhaps the ONH, does not stop at ECM remodeling but also TGF-β is a putative positive regulator of neuronal survival.

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