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Updated: Aug 2, 2026
An Alkali-burn Injury Model of Corneal Neovascularization in the Mouse
Published on: April 7, 2014
Induction of macrophage inflammatory protein-1alpha and vascular endothelial growth factor during inflammatory
1Department of Medical Biochemistry, Graduate School of Medical Sciences, Kyushu University, Maidashi, Fukuoka 812-8582, Japan. ogawainu@biochem1.med.kyushu-u.ac.jp
Abstract:
We predicted that the appearance of macrophages in inflammatory areas is necessary for angiogenic responses in various inflammatory diseases. Using a mouse inflammatory corneal model in which model mouse corneas were cauterized with silver nitrate, we examined the infiltration of macrophages immunohistochemically and the total area of neovascularization quantitively. The expression of macrophage inflammatory protein-1alpha (MIP-1alpha) and vascular endothelial growth factor (VEGF) levels were also examined. A day after cauterization, short capillaries began to develop into the corneal stroma, and after 4 or 5 days the neovascularization became maximal and then began to regress. The number of macrophages within the cauterized cornea increased to a maximum at day 3 and began to decrease at day 5. The number of infiltrated macrophages reached maximum at day 3. Both MIP-1alpha and VEGF protein levels increased markedly immediately after the chemical cauterization, and production of MIP-1alpha (85.8 pg/4 corneas) and VEGF (206.5 pg/4 corneas) was maximal at 1 day and 0.5 day after cauterization, respectively. MIP-1alpha and VEGF mRNA levels also increased at 0.5 day after cauterization. In situ hybridization showed that MIP-1alpha was localized in corneal epithelial cells, and VEGF was localized in corneal epithelial cells and infiltrating inflammatory cells. MIP-1alpha and VEGF may have an important role in recruiting macrophages and neovascularization.
Insights
Macrophage infiltration is crucial for blood vessel growth (angiogenesis) in inflammatory eye diseases. Macrophage inflammatory protein-1alpha (MIP-1alpha) and vascular endothelial growth factor (VEGF) play key roles in this process.
Area of Science:
- Ophthalmology
- Immunology
- Angiogenesis Research
Background:
- Macrophage infiltration is observed in inflammatory conditions.
- Angiogenic responses are critical in various inflammatory diseases.
Purpose of the Study:
- To investigate the necessity of macrophage appearance for angiogenic responses in a mouse corneal inflammatory model.
- To examine the roles of macrophage inflammatory protein-1alpha (MIP-1alpha) and vascular endothelial growth factor (VEGF) in this process.
Main Methods:
- A mouse inflammatory corneal model was induced using silver nitrate cauterization.
- Macrophage infiltration was assessed immunohistochemically.
- Neovascularization was quantified.
- MIP-1alpha and VEGF protein and mRNA levels were measured.
- In situ hybridization was used to determine the localization of MIP-1alpha and VEGF.
Main Results:
- Neovascularization peaked at days 4-5 post-cauterization and subsequently regressed.
- Macrophage numbers peaked at day 3 post-cauterization.
- MIP-1alpha and VEGF protein and mRNA levels increased significantly after cauterization, with peak production at 0.5-1 day.
- MIP-1alpha was localized in corneal epithelial cells, while VEGF was found in epithelial cells and infiltrating inflammatory cells.
Conclusions:
- Macrophage infiltration is necessary for angiogenic responses in this inflammatory corneal model.
- MIP-1alpha and VEGF are key mediators involved in recruiting macrophages and promoting neovascularization.
- These findings suggest potential therapeutic targets for inflammatory eye diseases.
