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Updated: May 21, 2026
The Corneal Micropocket Assay: A Model of Angiogenesis in the Mouse Eye
Published on: August 16, 2014
Activated macrophages induce neovascularization through upregulation of MMP-9 and VEGF in rat corneas
Zhan-rong Li1, Yong-ping Li, Miao-li Lin
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.
Purpose:
To explore the mechanisms of activated macrophages (A-Mφ) involved in corneal angiogenesis.
Methods:
Activated macrophages were elicited by mineral oil lumbar injection and implanted into corneal micropockets in rats for the treatment group, A-Mφ, and phosphate-buffered saline group as control. Corneal changes were observed with a slit lamp microscope, and histopathological features were evaluated by immunofluorescence. Reverse transcription-polymerase chain reaction was used to detect the relative expression of angiogenesis-associated factors and inflammatory mediators in the activated macrophages and corneal tissue after implantation.
Results:
Immunofluorescence showed that peritoneal cells expressed antigens of cluster of differentiation 68 (CD68, ED1), matrix metalloproteinases-9 (MMP-9), and vascular endothelial growth factor (VEGF). Activated macrophages significantly induced corneal neovascularization (CNV), which peaked on day 5, whereas the control group and normal corneas showed less CNV. The activated macrophages and corneal tissue after implantation expressed the angiogenesis-related factors, such as cyclooxygenase-2, platelet-derived growth factor, transforming growth factor beta, interleukin-1 alpha, MMP-9, and VEGF in messenger RNA (mRNA). However, mRNA expression of MMP-9 and VEGF differed significantly only in the cornea between the A-Mφ group and phosphate-buffered saline group 5 days after the implantation. MMP-9 and VEGF expression of mRNA and protein was higher in the A-Mφ group than that in the control group and normal corneas.
Conclusions:
Activated macrophages induce obvious CNV and related mechanisms, which may be correlated with MMP-9 and VEGF autocrine in activated macrophages and upregulation of MMP-9 and VEGF in corneal tissue.
Insights
Activated macrophages significantly promote corneal neovascularization (CNV) by upregulating matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF). These factors are crucial in the mechanisms driving CNV development.
Area of Science:
- Ophthalmology
- Immunology
- Cell Biology
Background:
- Corneal angiogenesis (CNV) is a complex process involving inflammatory cells.
- Activated macrophages play a role in neovascularization, but their specific mechanisms in the cornea are not fully understood.
Purpose of the Study:
- To investigate the role and mechanisms of activated macrophages (A-Mφ) in corneal angiogenesis.
- To identify key molecular factors involved in A-Mφ-induced CNV.
Main Methods:
- Activated macrophages were implanted into rat corneal micropockets.
- Corneal neovascularization was assessed using slit lamp microscopy and histopathology.
- Expression of angiogenesis-related factors and inflammatory mediators was analyzed by RT-PCR and immunofluorescence.
Main Results:
- Activated macrophages significantly induced corneal neovascularization (CNV), peaking at day 5.
- Expression of angiogenesis factors like MMP-9 and VEGF (messenger RNA and protein) was significantly higher in A-Mφ-treated corneas.
- Activated macrophages expressed CD68, MMP-9, and VEGF antigens.
Conclusions:
- Activated macrophages are potent inducers of corneal neovascularization (CNV).
- The mechanism involves autocrine signaling of MMP-9 and VEGF by activated macrophages.
- Upregulation of MMP-9 and VEGF in corneal tissue contributes to A-Mφ-mediated CNV.
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