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Updated: Aug 28, 2025
A Mouse Model for Laser-induced Choroidal Neovascularization
Published on: December 27, 2015
Delayed regression of laser-induced choroidal neovascularization in TNFα-null mice
Hiroki Iwanishi1, Osamu Yamanaka1, Takayoshi Sumioka1
1Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan.
Abstract:
We investigated the effects of lacking TNFα on the development and regression of Argon-laser-induced choroidal neovascularization (CNV) in mice. We lasered ocular fundus for induction of CNV in both wild-type (WT) and TNFα-null (KO) mice. Fluorescence angiography was performed to examine the size of CNV lesions. Gene expression pattern of wound healing-related components was examined. The effects of exogenous TNFα on apoptosis of human retinal microvascular endothelial cells (HRMECs) and on the tube-like structure of the cells were investigated in vitro. The results showed that Argon-laser irradiation-induced CNV was significantly larger in KO mice than WT mice on Day 21, but not at other timepoints. Lacking TNFα increased neutrophil population in the lesion. The distribution of cleaved caspase3-labelled apoptotic cells was more frequently observed in the laser-irradiated tissue in a WT mouse as compared with a KO mouse. Exogenous TNFα induced apoptosis of HRMECs and accelerated regression of tube-like structure of HRMECs in cell culture. Taken together, TNFα gene knockout delays the regression of laser-induced CNV in mice. The mechanism underlying the phenotype might include the augmentation of neutrophil population in the treated tissue and attenuation of vascular endothelial cell apoptosis.
Insights
Tumor necrosis factor-alpha (TNFα) deficiency delays the regression of choroidal neovascularization (CNV) in mice. This occurs due to increased neutrophils and reduced apoptosis in vascular endothelial cells.
Area of Science:
- Ophthalmology
- Immunology
- Molecular Biology
Background:
- Choroidal neovascularization (CNV) is a major cause of vision loss.
- Tumor necrosis factor-alpha (TNFα) plays a role in inflammatory and immune responses.
- The specific role of TNFα in CNV development and regression remains unclear.
Purpose of the Study:
- To investigate the impact of TNFα deficiency on laser-induced CNV in mice.
- To elucidate the underlying mechanisms of TNFα's role in CNV.
Main Methods:
- Induction of CNV in wild-type (WT) and TNFα-null (KO) mice using Argon laser.
- Assessment of CNV lesion size via fluorescence angiography.
- Analysis of gene expression for wound healing components.
- In vitro studies on human retinal microvascular endothelial cells (HRMECs) with exogenous TNFα.
Main Results:
- CNV lesions were significantly larger in KO mice compared to WT mice at Day 21.
- TNFα deficiency led to an increased neutrophil population within the CNV lesions.
- Reduced apoptosis of vascular endothelial cells was observed in KO mice.
- Exogenous TNFα induced apoptosis and inhibited tube formation in HRMECs in vitro.
Conclusions:
- TNFα gene knockout delays the regression of laser-induced CNV in mice.
- This delay is associated with increased neutrophils and decreased apoptosis of vascular endothelial cells.
- TNFα plays a crucial role in the resolution of CNV.
