Related Experiment Video

Updated: May 20, 2025

A Mouse Model for Laser-induced Choroidal Neovascularization
07:08

A Mouse Model for Laser-induced Choroidal Neovascularization

Published on: December 27, 2015

17.6K

The Role of the Mitogen-Activated Protein Kinase Pathway in the Development of Laser-Induced Choroidal

Sun Young Jang1, Jin Young Yang2, Jin Hwan Park1

  • 1Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon 14584, Republic of Korea.

International Journal of Molecular Sciences
|March 27, 2025
PubMed

Insights

The mitogen-activated protein kinase (MAPK) pathway drives choroidal neovascularization (CNV). Sprouty 2 (SPRY2) inhibits MAPK, significantly reducing CNV lesions and inflammation, offering a potential therapeutic strategy.

Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Cell Biology

Background:

  • The role of the mitogen-activated protein kinase (MAPK) pathway in choroidal neovascularization (CNV) is not fully understood.
  • Investigating specific MAPK pathways (ERK, JNK, p38) and their involvement in CNV pathogenesis is crucial.

Purpose of the Study:

  • To elucidate the involvement of ERK, JNK, and p38 pathways in CNV development.
  • To evaluate the therapeutic potential of Sprouty 2 (SPRY2), an MAPK inhibitor, in a mouse model of CNV.

Main Methods:

  • Laser-induced CNV mouse model.
  • Western blotting and immunostaining to analyze protein expression.
  • Immunofluorescence and co-immunostaining to assess protein localization and cellular associations.

Main Results:

  • Increased p-ERK and p-JNK expression observed in retinal and choroidal tissues post-CNV induction.
  • p-ERK colocalized with markers of angiogenesis, inflammation, and glial cells; p-JNK and p-p38 associated with angiogenesis and inflammation.
  • SPRY2 treatment significantly inhibited CNV lesion size, endothelial proliferation, fibrosis, and apoptosis compared to aflibercept, while preserving retinal pigment epithelium (RPE) integrity.
  • SPRY2 reduced CNV-related inflammation, epithelial-mesenchymal transition, and photoreceptor apoptosis.

Conclusions:

  • The MAPK pathway, particularly ERK and JNK, plays a significant role in CNV pathogenesis, mediating processes like Müller cell gliosis, angiogenesis, and inflammation.
  • SPRY2 demonstrates potent therapeutic effects by suppressing key CNV pathologies, highlighting its potential as a novel treatment targeting the MAPK pathway.
Keywords:
angiogenesischoroidal neovascularizationgliosisinflammationmitogen-activated protein kinasesprouty 2

More Related Videos

In Vivo Multimodal Imaging and Analysis of Mouse Laser-Induced Choroidal Neovascularization Model09:56

In Vivo Multimodal Imaging and Analysis of Mouse Laser-Induced Choroidal Neovascularization Model

Published on: January 21, 2018

9.1K
Müller Glia Cell Activation in a Laser-induced Retinal Degeneration and Regeneration Model in Zebrafish06:27

Müller Glia Cell Activation in a Laser-induced Retinal Degeneration and Regeneration Model in Zebrafish

Published on: October 27, 2017

9.7K

Related Concept Videos

MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.0K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.3K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.3K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K