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Updated: Jul 6, 2026
A Mouse Model for Laser-induced Choroidal Neovascularization
Published on: December 27, 2015
Metrnl inhibits choroidal neovascularization by attenuating the choroidal inflammation via inactivating the
Lanyue Zhang1, Youjian Li2, Zhengyu Wu2
1Department of Ophthalmology, Chongqing University Jiangjin Hospital, Chongqing, China.
Objective:
Choroidal neovascularization (CNV) represents the predominant form of advanced wet Age-related Macular Degeneration (wAMD). Macrophages play a pivotal role in the pathological progression of CNV. Meteorin-like (Metrnl), a novel cytokine known for its anti-inflammatory properties in macrophages, is the focus of our investigation into its mechanism of action and its potential to impede CNV progression.
Methods:
Cell viability was evaluated through CCK-8 and EdU assays following Metrnl treatment. Expression levels of inflammatory cytokines and proteins were assessed using quantitative reverse-transcription polymerase chain reaction(qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot techniques. Protein-protein interactions were identified through protein mass spectrometry and co-immunoprecipitation (Co-IP). Additionally, in vivo and in vitro neovascularization models were employed to evaluate angiogenesis.
Results:
Our results revealed downregulated Metrnl levels in the choroid-sclera complex of CNV mice, the aqueous humor of wAMD patients, and activated macrophages. Metrnl overexpression demonstrated a reduction in pro-inflammatory cytokine production, influenced endothelial cell function, and suppressed angiogenesis in choroid explants and CNV models. Through protein mass spectrometry and Co-IP, we confirmed Metrnl binds to UCHL-1 to modulate the NF-κB signaling pathway. This interaction inhibited the transcription and expression of pro-inflammatory cytokines, ultimately suppressing angiogenesis.
Conclusion:
In summary, our findings indicate that Metrnl down-regulates macrophage pro-inflammatory cytokine secretion via the UCHL-1/NF-κB signaling pathway. This mechanism alleviates the inflammatory microenvironment and effectively inhibits choroidal neovascularization.
Insights
Meteorin-like (Metrnl) suppresses inflammation in macrophages by interacting with UCHL-1, inhibiting the NF-κB pathway. This mechanism reduces pro-inflammatory cytokines, offering a potential therapeutic strategy for wet Age-related Macular Degeneration (wAMD) and choroidal neovascularization (CNV).
Area of Science:
- Ophthalmology
- Immunology
- Molecular Biology
Background:
- Choroidal neovascularization (CNV) is a primary cause of advanced wet Age-related Macular Degeneration (wAMD).
- Macrophages are key drivers in the pathological progression of CNV.
- Meteorin-like (Metrnl) is a novel cytokine with known anti-inflammatory properties in macrophages.
Purpose of the Study:
- To investigate the mechanism of action of Metrnl in macrophages.
- To evaluate Metrnl's potential to inhibit CNV progression.
- To elucidate the molecular pathways targeted by Metrnl in the context of CNV.
Main Methods:
- Cell viability assays (CCK-8, EdU) were used to assess Metrnl's effect on cell health.
- Quantitative reverse-transcription polymerase chain reaction (qRT-PCR), ELISA, and western blot were employed to measure inflammatory markers.
- Protein mass spectrometry and co-immunoprecipitation (Co-IP) identified protein interactions, and in vivo/in vitro models assessed angiogenesis.
Main Results:
- Metrnl levels were found to be downregulated in CNV models and wAMD patients.
- Metrnl overexpression reduced pro-inflammatory cytokines and suppressed angiogenesis in experimental models.
- Metrnl was confirmed to bind UCHL-1, modulating the NF-κB signaling pathway to inhibit pro-inflammatory gene expression.
Conclusions:
- Metrnl downregulates macrophage pro-inflammatory cytokine secretion through the UCHL-1/NF-κB signaling pathway.
- This action alleviates the inflammatory microenvironment, thereby inhibiting choroidal neovascularization.
- Metrnl presents a promising therapeutic target for managing wAMD and related CNV.
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