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Juan Qu, Tatjana Jakobs; Optic Nerve Head Astrocytes Increase Expression Of Tenascin C In Response To Injury. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2009.
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Tennascin c (Tnc) is one of the astrocyte-secreted extracellular matrix proteins of the central nervous system. It is involved in the remodeling of the central nervous system, both during development and in adult. We previously reported that mouse optic nerve head astrocytes go through a two-stage morphological remodeling after optic nerve crush. It changes the architecture of the optic nerve head. In this present study, we tested the hypothesis that Tnc is secreted by optic nerve head astrocytes and may contribute to the tissue remodeling in response to crush injury and in experimental glaucoma.
Optic nerve crush was conducted in 2-3 months old C57Bl/6 mice and GFAP-Tomato mice. The optic nerve in one eye was crushed and the contralateral eye served as control. Eyes of 10-12 months old DBA/2J mice that had developed moderate or severe glaucoma were also studied. Eyes of age-matched DBA/2J mice that had no glaucoma served as control. Q-PCR using RNA extracted from the whole optic nerve head and single-cell RT-PCR using acutely dissociated optic nerve head astrocytes were performed to determine the mRNA level of Tnc. Immunohistochemistry was performed on transverse and longitudinal sections of optic nerve head to localize Tnc protein.
The mRNA level of Tnc in the whole optic nerve head of the crushed eye significantly increased 24 hours after injury. The up regulation was sustained for at least one week. It returned to resting levels by three weeks. Single-cell RT-PCR of optic nerve head astrocytes confirmed that the source of the up regulation was in astrocytes. In the glaucoma model, the mRNA level of Tnc also significantly increased, especially the eyes with moderate glaucoma. Immunohistochemistry for Tnc showed clear enhancement of Tnc protein in the optic nerve head both after optic nerve crush and in glaucoma.
Optic nerve head astrocytes increase their expression of Tnc in response to crush injury and in glaucoma. This indicates that astrocytes actively respond to injury and disease. In addition, Tnc can interact with extracellular matrix protein membrane receptors such as integrin, which regulates cell adhesion, migration, and proliferation. Therefore Tnc may play an important role in the optic nerve head tissue remodeling in response to injury.
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