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MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges
Petros Moustardas1, Daniel Aberdam2,3, Neil Lagali1,4
1Division of Ophthalmology, Department of Biomedical and Clinical Sciences, Linköping University, 58185 Linköping, Sweden.
Abstract:
Mitogen-activated protein kinase (MAPK) pathways represent ubiquitous cellular signal transduction pathways that regulate all aspects of life and are frequently altered in disease. Once activated through phosphorylation, these MAPKs in turn phosphorylate and activate transcription factors present either in the cytoplasm or in the nucleus, leading to the expression of target genes and, as a consequence, they elicit various biological responses. The aim of this work is to provide a comprehensive review focusing on the roles of MAPK signaling pathways in ocular pathophysiology and the potential to influence these for the treatment of eye diseases. We summarize the current knowledge of identified MAPK-targeting compounds in the context of ocular diseases such as macular degeneration, cataract, glaucoma and keratopathy, but also in rare ocular diseases where the cell differentiation, proliferation or migration are defective. Potential therapeutic interventions are also discussed. Additionally, we discuss challenges in overcoming the reported eye toxicity of some MAPK inhibitors.
Insights
Mitogen-activated protein kinase (MAPK) pathways are crucial in cell signaling and are implicated in eye diseases. This review explores MAPK roles in ocular pathophysiology and therapeutic potential for conditions like macular degeneration and glaucoma.
Area of Science:
- Cell Biology
- Molecular Biology
- Ophthalmology
Background:
- Mitogen-activated protein kinase (MAPK) pathways are fundamental cellular signal transduction cascades involved in diverse biological processes.
- Dysregulation of MAPK signaling is frequently observed in various disease states, including ocular pathologies.
- MAPKs, upon activation by phosphorylation, regulate transcription factors, influencing gene expression and cellular responses.
Purpose of the Study:
- To provide a comprehensive review of the roles of MAPK signaling pathways in ocular pathophysiology.
- To explore the therapeutic potential of targeting MAPK pathways for treating eye diseases.
- To summarize current knowledge on MAPK-targeting compounds for ocular conditions and discuss challenges.
Main Methods:
- Literature review of scientific publications on MAPK pathways and ocular diseases.
- Synthesis of information on MAPK involvement in common and rare eye conditions.
- Analysis of existing and potential therapeutic interventions targeting MAPK signaling in ophthalmology.
Main Results:
- MAPK pathways play significant roles in the pathophysiology of macular degeneration, cataract, glaucoma, and keratopathy.
- Specific MAPK-targeting compounds have been identified for potential therapeutic use in these ocular diseases.
- Challenges include the eye toxicity associated with some MAPK inhibitors, necessitating careful consideration for therapeutic development.
Conclusions:
- MAPK signaling pathways are critical targets for therapeutic intervention in a range of ocular diseases.
- Further research is needed to optimize MAPK-targeted therapies, addressing efficacy and mitigating potential toxicity.
- Understanding MAPK roles in cell differentiation, proliferation, and migration is key to treating rare ocular disorders.
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