Loss of the extracellular matrix molecule tenascin-C leads to absence of reactive gliosis and promotes anti-inflammatory cytokine expression in an autoimmune glaucoma mouse model

Wiemann, Susanne; Reinhard-Recht, Jaqueline; Reinehr, Sabrina; Cibir, Zuelal; Joachim, Stephanie C; Faissner, Andréas

doi:10.1101/2020.04.28.064758

Cited by 2 publications

(2 citation statements)

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“…This manuscript has been released as a pre-print at bioRxiv, ( 122 ). The authors thank Stephanie Chun, Anja Coenen, Sabine Kindermann, Franziska Mennes, Annalena Pamp, and Marion Voelzkow for excellent technical assistance.…”

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confidence: 99%

Loss of the Extracellular Matrix Molecule Tenascin-C Leads to Absence of Reactive Gliosis and Promotes Anti-inflammatory Cytokine Expression in an Autoimmune Glaucoma Mouse Model

et al. 2020

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Previous studies demonstrated that retinal damage correlates with a massive remodeling of extracellular matrix (ECM) molecules and reactive gliosis. However, the functional significance of the ECM in retinal neurodegeneration is still unknown. In the present study, we used an intraocular pressure (IOP) independent experimental autoimmune glaucoma (EAG) mouse model to examine the role of the ECM glycoprotein tenascin-C (Tnc). Wild type (WT ONA) and Tnc knockout (KO ONA) mice were immunized with an optic nerve antigen (ONA) homogenate and control groups (CO) obtained sodium chloride (WT CO, KO CO). IOP was measured weekly and electroretinographies were recorded at the end of the study. Ten weeks after immunization, we analyzed retinal ganglion cells (RGCs), glial cells, and the expression of different cytokines in retina and optic nerve tissue in all four groups. IOP and retinal function were comparable in all groups. Although RGC loss was less severe in KO ONA, WT as well as KO mice displayed a significant cell loss after immunization. Compared to KO ONA, less βIII-tubulin + axons, and downregulated oligodendrocyte markers were noted in WT ONA optic nerves. In retina and optic nerve, we found an enhanced GFAP + staining area of astrocytes in immunized WT. A significantly higher number of retinal Iba1 + microglia was found in WT ONA, while a lower number of Iba1 + cells was observed in KO ONA. Furthermore, an increased expression of the glial markers Gfap, Iba1, Nos2 , and Cd68 was detected in retinal and optic nerve tissue of WT ONA, whereas comparable levels were observed in KO ONA. In addition, pro-inflammatory Tnfa expression was upregulated in WT ONA, but downregulated in KO ONA. Vice versa, a significantly increased anti-inflammatory Tgfb1 expression was measured in KO ONA animals. We conclude that Tnc plays an important role in glial and inflammatory response during retinal neurodegeneration. Our results provide evidence that Tnc is involved in glaucomatous damage by regulating retinal glial activation and cytokine release. Thus, this transgenic EAG mouse model for the first time offers the possibility to investigate IOP-independent glaucomatous damage in direct relation to ECM remodeling.

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Loss of the Extracellular Matrix Molecule Tenascin-C Leads to Absence of Reactive Gliosis and Promotes Anti-inflammatory Cytokine Expression in an Autoimmune Glaucoma Mouse Model

et al. 2020

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“…146,147 Despite increases in transcription in response to mechanical stretch, tenascin C knockout mice do not show any difference in IOP measurements compared with wild-type littermates. 148,149…”

Section: Tenascin Cmentioning

confidence: 99%

Pathogenesis of glaucoma: Extracellular matrix dysfunction in the trabecular meshwork‐A review

Keller

Peters

2022

Clinical Exper Ophthalmology

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The trabecular meshwork regulates aqueous humour outflow from the anterior chamber of the eye. It does this by establishing a tunable outflow resistance, defined by the interplay between cells and their extracellular matrix (ECM) milieu, and the molecular interactions between ECM proteins. During normal tissue homeostasis, the ECM is remodelled and trabecular cell behaviour is modified, permitting increased aqueous fluid outflow to maintain intraocular pressure (IOP) within a relatively narrow physiological pressure.Dysfunction in the normal homeostatic process leads to increased outflow resistance and elevated IOP, which is a primary risk factor for glaucoma. This review delineates some of the changes in the ECM that lead to gross as well as some more subtle changes in the structure and function of the ECM, and their impact on trabecular cell behaviour. These changes are discussed in the context of outflow resistance and glaucoma.

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Loss of the extracellular matrix molecule tenascin-C leads to absence of reactive gliosis and promotes anti-inflammatory cytokine expression in an autoimmune glaucoma mouse model

Abstract: Words Abstract: 350 (maximum 350 words) Words Manuscript: 6844 (maximum 12.000 words)

Cited by 2 publications

References 72 publications

Loss of the Extracellular Matrix Molecule Tenascin-C Leads to Absence of Reactive Gliosis and Promotes Anti-inflammatory Cytokine Expression in an Autoimmune Glaucoma Mouse Model

Loss of the Extracellular Matrix Molecule Tenascin-C Leads to Absence of Reactive Gliosis and Promotes Anti-inflammatory Cytokine Expression in an Autoimmune Glaucoma Mouse Model

Pathogenesis of glaucoma: Extracellular matrix dysfunction in the trabecular meshwork‐A review

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