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Updated: Jun 28, 2026

Ex Vivo Corneal Organ Culture Model for Wound Healing Studies
Published on: February 15, 2019
Upregulation of tumor necrosis factor receptor 1 and TNF-alpha converting enzyme during corneal wound healing
Tohru Sakimoto1,2, Ai Yamada3, Hitoshi Kanno4
1Department of Ophthalmology, Nihon University School of Medicine, Tokyo, Japan. torusaki@med.nihon-u.ac.jp.
Purpose:
To elucidate tumor necrosis factor (TNF) receptor-1 (TNFR1) and TNF-alpha converting enzyme (TACE) involvement during corneal wound healing.
Methods:
The corneas of BALB/c mice cornea were scarred by alkali burns using filter paper dipped in 1N NaOH solution. TACE and TNFR1 expression in the alkali-burned corneas were evaluated by immunohistochemistry (total, 16 eyes). Using cultured fibroblasts (human) and macrophages (mice), we evaluated the release of soluble TNF-alpha (sTNF-alpha) and soluble TNFR1 (sTNFR1) in the supernatant by enzyme-linked immunosorbent assay after stimulating TACE activity with phorbol myristate acetate (PMA).
Results:
In alkali-burned corneas, both TACE and TNFR1 expression were observed in the stromal cells after the acute phase of wound healing response. In macrophage-cultured supernatant, both sTNF-alpha and sTNFR1 release were promoted by PMA stimulation. On the other hand, only sTNFR1 released by PMA stimulation was observed in fibroblast-cultured supernatant.
Conclusions:
TACE and TNFR1 were expressed mainly after the acute phase of corneal wound healing. The TACE-dependent extracellular release of sTNFR1 was recognized in cultured fibroblasts and macrophages.
Insights
Tumor necrosis factor-alpha converting enzyme (TACE) and tumor necrosis factor receptor-1 (TNFR1) are involved in corneal wound healing. TACE facilitates the release of soluble TNFR1 from fibroblasts and macrophages post-injury.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Corneal wound healing is a complex process involving inflammatory mediators.
- Tumor necrosis factor (TNF) signaling plays a role in tissue repair and inflammation.
Purpose of the Study:
- To investigate the involvement of TNF-alpha converting enzyme (TACE) and TNF receptor-1 (TNFR1) in corneal wound healing.
- To determine the expression patterns and functional roles of TACE and TNFR1 in the corneal healing process.
Main Methods:
- Corneal alkali burns were induced in BALB/c mice.
- TACE and TNFR1 expression was assessed using immunohistochemistry.
- Soluble TNF-alpha (sTNF-alpha) and soluble TNFR1 (sTNFR1) release was measured in cultured human fibroblasts and mouse macrophages stimulated with phorbol myristate acetate (PMA).
Main Results:
- TACE and TNFR1 expression were detected in stromal cells of alkali-burned corneas after the acute phase.
- PMA stimulation promoted the release of both sTNF-alpha and sTNFR1 from macrophages.
- PMA stimulation induced sTNFR1 release from fibroblasts, but not sTNF-alpha.
Conclusions:
- TACE and TNFR1 are primarily expressed after the acute phase of corneal wound healing.
- TACE mediates the extracellular release of sTNFR1 in both fibroblasts and macrophages.
- These findings highlight the role of the TACE-TNFR1 axis in post-injury corneal tissue remodeling.
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