Tenascin C regulates proliferation and differentiation processes during embryonic retinogenesis and modulates the de-differentiation capacity of Muller glia by influencing growth factor responsiveness and the extracellular matrix compartment

The retina represents an ideal model system for studying developmental processes during morphogenesis. The knowledge of the precise regulation and combination of genetic pre-dispositions and environmental circumstances enables the understanding of pathologies and the subsequent development or/and improvement of therapeutic strategies. This study focused on the functional analysis of the extracellular matrix (ECM) molecule Tenascin C (Tnc) in the retinal stem/progenitor cell environment. In this perspective, a Tnc(-/-) mouse was examined for potential alterations in proliferation and differentiation programs by using immunohistochemistry, RT-PCR analysis and bioassays. It could be shown that both cycling G2-phase cells and early post-mitotic neurons were significantly increased in the retina due to Tnc-deficiency. Further investigations suggested that Tnc regulates these processes via the Wnt-signaling cascade. Therapeutic approaches in the treatment of degenerative diseases often integrate cell-replacement strategies. Retinal Muller glia cells represent the glia of the retina and are described to possess the ability to re-enter the cell cycle and generate neurons in response to injury. In this study, the de-differentiation was induced by FGF2. It was found out that Tnc influences the dedifferentiation behavior of adherent Muller glia in vitro. Moreover, it was interesting to investigate the effect of the absence of Tnc on the composition of other components of the ECM. A special focus lay on the expression of a specifically sulfated carbohydrate motif on chondroitin sulfate glycosaminoglycan chains, which can be detected with the mAb 473HD. It was possible to note a significant increase of this particular chondroitin sulfate in the Tnc-deficient ECM. (C) 2012 Elsevier Inc. All rights reserved.