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Updated: Apr 27, 2026
In Vivo Multimodal Imaging and Analysis of Mouse Laser-Induced Choroidal Neovascularization Model
Published on: January 21, 2018
Therapeutic potential of semaphorin 3E for the treatment of choroidal neovascularization
Kenji Suda1, Congrong Guo1, Akio Oishi1
1Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Purpose:
We investigated the effects of semaphorin 3E (Sema3E)/PlexinD1 signaling in the development of choroidal neovascularization (CNV) and explored the therapeutic potential of the pathway.
Methods:
We used a laser-induced CNV model in the mouse. The expression of Sema3E and PlexinD1 was evaluated with immunohistochemistry, real-time RT-PCR, and Western blotting. After the intravitreal injection of Sema3E, the CNV size was measured on immunostained flat mounts. The CNV size was compared between inducible PlexinD1 homozygous mice and heterozygous knockout mice.
Results:
The presence of PlexinD1 was confirmed immunohistochemically in the endothelial cells of CNV. The expression of PlexinD1 mRNA was elevated after laser photocoagulation with its peak expression at day 5 (1.72 times, compared to baseline; P < 0.01). The intravitreal injection of recombinant Sema3E decreased the CNV size (16,320.9 ± 8316.0 μm(2) in the control eyes versus 9487.4 ± 4424.1 μm(2) in the eyes administered 0.1-μg Sema3E, P < 0.01). This inhibitory effect of Sema3E in the formation of CNV was canceled in the inducible PlexinD1 knockout mice (24,920.8 ± 24,684.8 μm(2) in homozygous knockout mice and 13,152.6 ± 7973.0 μm(2) in heterozygous knockout mice, P = 0.014).
Conclusions:
These results indicate that Sema3E-PlexinD1 signaling is involved in the development of CNV. Stimulation of the pathway has therapeutic potential for CNV. Further studies are needed to evaluate the effects for clinical applications.
Insights
Semaphorin 3E (Sema3E) signaling via PlexinD1 inhibits choroidal neovascularization (CNV) development. Targeting this pathway offers potential therapeutic benefits for treating CNV.
Area of Science:
- Ophthalmology
- Molecular Biology
- Neovascularization Research
Background:
- Choroidal neovascularization (CNV) is a major cause of vision loss.
- Understanding the molecular mechanisms regulating CNV is crucial for developing effective treatments.
- The role of semaphorin 3E (Sema3E) and its receptor PlexinD1 in ocular neovascularization requires further investigation.
Purpose of the Study:
- To investigate the role of Sema3E/PlexinD1 signaling in the pathogenesis of laser-induced CNV in a mouse model.
- To explore the therapeutic potential of modulating the Sema3E/PlexinD1 pathway for CNV treatment.
Main Methods:
- Laser-induced CNV model in mice.
- Evaluation of Sema3E and PlexinD1 expression using immunohistochemistry, real-time RT-PCR, and Western blotting.
- Assessment of CNV size following intravitreal injection of Sema3E and in inducible PlexinD1 knockout mice.
Main Results:
- PlexinD1 was localized to endothelial cells within CNV lesions.
- PlexinD1 mRNA expression significantly increased post-laser photocoagulation, peaking at day 5.
- Intravitreal administration of Sema3E markedly reduced CNV size (P < 0.01).
- The inhibitory effect of Sema3E on CNV was abolished in PlexinD1 homozygous knockout mice.
Conclusions:
- Sema3E-PlexinD1 signaling plays a significant role in the development of choroidal neovascularization.
- Targeting the Sema3E-PlexinD1 pathway demonstrates therapeutic potential for CNV.
- Further research is warranted to translate these findings into clinical applications for CNV treatment.
