Loss of tenascin X gene function impairs injury-induced stromal angiogenesis in mouse corneas

Area of Science:

• Ophthalmology
• Molecular Biology
• Immunology

Background:

• Corneal stromal angiogenesis is a complex process involving inflammatory responses and growth factors.
• Tenascin X (Tnx) is an extracellular matrix protein implicated in tissue repair and inflammation.
• The specific role of Tnx in corneal neovascularization remains largely unexplored.

Purpose of the Study:

• To investigate the contribution of Tnx gene expression to corneal stromal angiogenesis.
• To evaluate the impact of Tnx deficiency on vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGFβ1) expression in ocular cells.
• To elucidate the role of Tnx in regulating inflammatory cell infiltration and neovascularization in the injured cornea.

Main Methods:

• Utilized tenascin X knockout (Tnx KO) and wild-type (WT) mice.
• Induced central corneal stromal cauterization to stimulate neovascularization.
• Employed histological, immunohistochemical, and quantitative RT-PCR analyses.
• Assessed gene and protein expression of Tnx, VEGF-A, VEGF-B, and TGFβ1 in corneal tissues and cultured ocular fibroblasts and macrophages.

Main Results:

• Tnx expression was upregulated in cauterized corneas.
• Tnx deficiency in KO mice led to attenuated macrophage invasion, reduced VEGF-A mRNA expression, and decreased neovascularization compared to WT mice.
• Loss of Tnx upregulated in vivo mRNA expression of anti-angiogenic VEGF-B but not VEGF-A.
• Tnx deficiency downregulated TGFβ1 mRNA expression in cultured ocular fibroblasts and VEGF-A in macrophages.

Conclusions:

• Tnx gene expression significantly contributes to promoting corneal stromal angiogenesis.
• Tnx facilitates neovascularization by upregulating VEGF-A in macrophages and TGFβ1 in ocular fibroblasts, alongside enhancing macrophage invasion.
• Tnx also plays a role in suppressing anti-angiogenic VEGF-B expression in vivo.