MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges

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.

Host-defence caerin 1.1 and 1.9 peptides suppress glioblastoma U87 and U118 cell proliferation through the modulation of mitochondrial respiration and induce the downregulation of CHI3L1

“…This phenomenon has been observed in immunotherapies that regulate various signalling pathways. For instance, tamoxifen demonstrates this effect in estrogen receptor signalling [47], while several MEK inhibitors exhibit biphasic effects in the MAPK/ ERK pathway [48][49][50].…”

Increased intraocular inflammation in retinal vein occlusion is independent of circulating immune mediators and is involved in retinal oedema

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Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

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