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Updated: Aug 15, 2025
A Mouse Model for Laser-induced Choroidal Neovascularization
Published on: December 27, 2015
MD2 Inhibits Choroidal Neovascularization via Antagonizing TLR4/MD2 Mediated Signaling Pathway
Qi Wu1,2, Zhang Chen3, Chenxin Wu1,2
1School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Purpose:
To explore the pathological mechanism of Toll-like receptor 4 (TLR4) mediating neovascular age-related macular degeneration (nAMD) and the potential role of the TLR4 coreceptor myeloid differentiation protein 2 (MD2).
Methods:
In the study, we inhibited MD2 with the chalcone derivative L2H17 and we utilized a laser-induced choroidal neovascularization (CNV) mouse model and Tert-butyl hydroperoxide (TBHP)-challenged rhesus choroid-retinal endothelial (RF/6A) cells to assess the effect of MD2 blockade on CNV.
Results:
Inhibiting MD2 with L2H17 reduced angiogenesis in CNV mice, and significantly protected against retinal dysfunction. In retina and choroid/retinal pigment epithelium (RPE) tissues, L2H17 reduced phospho-ERK, phospho-P65 but not phospho-P38, phospho-JNK, and reduced the transcriptional levels of IL-6, TNF-α, ICAM-1 but not VCAM-1. L2H17 could protect RF/6A against TBHP-induced inflammation, oxidative stress, and apoptosis, via inhibiting the TLR4/MD2 signaling pathway and the following downstream mitogen-activated protein kinase (MAPK) and nuclear transcription factor-κB (NF-κB) activation.
Conclusions:
Inhibiting MD2 with L2H17 significantly reduced CNV, suppressed inflammation, and oxidative stress by antagonizing TLR4/MD2 pathway in an MD2-dependent manner. MD2 may be a potential therapeutic target and L2H17 may offer an alternative treatment strategy for nAMD.
Insights
Inhibiting myeloid differentiation protein 2 (MD2) with L2H17 reduced neovascular age-related macular degeneration (nAMD) and associated inflammation. This suggests MD2 is a therapeutic target for nAMD treatment.
Area of Science:
- Ophthalmology
- Immunology
- Molecular Biology
Background:
- Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss.
- Toll-like receptor 4 (TLR4) signaling is implicated in nAMD pathogenesis.
- The role of the TLR4 coreceptor, myeloid differentiation protein 2 (MD2), in nAMD requires further elucidation.
Purpose of the Study:
- To investigate the pathological mechanism of TLR4 in mediating nAMD.
- To explore the potential therapeutic role of targeting MD2 in nAMD.
Main Methods:
- A chalcone derivative, L2H17, was used to inhibit MD2.
- A laser-induced choroidal neovascularization (CNV) mouse model was employed.
- Tert-butyl hydroperoxide (TBHP)-challenged rhesus choroid-retinal endothelial (RF/6A) cells were used to assess MD2 blockade effects.
Main Results:
- L2H17 administration reduced angiogenesis in CNV mice and protected against retinal dysfunction.
- L2H17 decreased key inflammatory markers (phospho-ERK, phospho-P65, IL-6, TNF-α, ICAM-1) in retinal tissues.
- L2H17 protected RF/6A cells from TBHP-induced inflammation, oxidative stress, and apoptosis via TLR4/MD2 pathway inhibition.
Conclusions:
- Inhibition of MD2 with L2H17 effectively reduced CNV, inflammation, and oxidative stress in an MD2-dependent manner.
- MD2 represents a promising therapeutic target for nAMD.
- L2H17 shows potential as an alternative treatment strategy for nAMD.
