The Role of the Mitogen-Activated Protein Kinase Pathway in the Development of Laser-Induced Choroidal Neovascularization
Open accessAbstract
The role of the mitogen-activated protein kinase (MAPK) pathway in choroidal neovascularization (CNV) remains unclear. This study investigates the involvement of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 pathways in CNV development, as well as the therapeutic potential of sprouty 2 (SPRY2), an MAPK inhibitor, in a laser-induced mouse model. The expressions of ERK, JNK, and p38 proteins were analyzed using Western blotting and immunostaining. Immunofluorescence imaging revealed increased p-ERK and p-JNK expression in the retina, retinal pigment epithelium (RPE), and choroid up to day 7. Co-immunostaining showed p-ERK colocalized with CD31, CD11b, F4/80, cytokeratin, and GFAP in the retina, while p-JNK and p-p38 were associated with angiogenesis and inflammation throughout the retina and choroid. Compared to aflibercept, SPRY2 administration significantly inhibited CNV lesions, endothelial proliferation, fibrosis, and apoptosis, while better-preserving RPE integrity. SPRY2-treated mice showed a stronger reduction in CNV-related inflammation, epithelial-mesenchymal transition, and photoreceptor apoptosis. These results highlight the MAPK pathway's role in CNV pathogenesis, with ERK primarily mediating Müller cell gliosis and JNK, contributing to angiogenesis and inflammation. SPRY2 effectively suppressed CNV lesions, supporting its potential as a therapeutic target for CNV treatment via MAPK pathway modulation.
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MAPK signaling is involved in the progression of CNV.
“In our previous study, we demonstrated that MAPK signaling is involved in the progression of CNV 25 .”
From rAAV-mediated Multi-miRNA Delivery Targeting MAPK Pathway Suppresses Laser-induced Choroidal Neovascularization in Mice (2026) · cites this paper as [25]
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- Authors
- Jang, S. Y., Yang, J. Y., Park, J. H., Kim, Y., An, S., Jung, W. H., Park, J.-W., Han, J. W., Kim, J. H., Park, H. S., Lyu, J., & Park, T. K.
- Affiliations
- Soonchunhyang University Hospital Bucheon (KR)
- Gachon University (KR)
- Konyang University (KR)
- Corresponding author
- Lyu, Jungmook
- Park, Tae Kwann
- ORCID
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2025-03-13
- Volume
- 26
- Issue
- 6
- Pages
- 2585
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC11942168
- OpenAlex
- W4408412391
- Cited by
- 7
- References
- 45
- Citations by year
- 2026: 5 · 2025: 2
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Research Council of Science and Technology (GTL24021-201, RS-2022-KH125938)
- Ministry of Health and Welfare (GTL24021-201, RS-2022-KH125938)
- Soonchunhyang University (GTL24021-201, RS-2022-KH125938)
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Keywords
- choroidal neovascularization, MAPK signaling, ERK, JNK, p38 MAPK, Sprouty2, MAPK inhibitors, laser-induced CNV, retinal pigment epithelium, Müller cell gliosis, choroidal angiogenesis, inflammation, epithelial-mesenchymal transition, photoreceptor apoptosis, aflibercept
- MeSH terms
- Animals, Choroid, Disease Models, Animal, Lasers, Male, Membrane Proteins, Mice, Inbred C57BL, Recombinant Fusion Proteins, Retina, Apoptosis, Choroidal Neovascularization, Mitogen-Activated Protein Kinases, MAP Kinase Signaling System, Receptors, Vascular Endothelial Growth Factor, Intracellular Signaling Peptides and Proteins, Mice, Retinal Pigment Epithelium
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