{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:18:57Z","timestamp":1792174737387,"version":"4.4.0"},"reference-count":231,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T00:00:00Z","timestamp":1676332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"EJP-RD","award":["EJPRD20-135"],"award-info":[{"award-number":["EJPRD20-135"]}]},{"name":"EJP-RD","award":["2020-00798"],"award-info":[{"award-number":["2020-00798"]}]},{"name":"EJP-RD","award":["CA-18116"],"award-info":[{"award-number":["CA-18116"]}]},{"name":"AAK-INSIGHT","award":["EJPRD20-135"],"award-info":[{"award-number":["EJPRD20-135"]}]},{"name":"AAK-INSIGHT","award":["2020-00798"],"award-info":[{"award-number":["2020-00798"]}]},{"name":"AAK-INSIGHT","award":["CA-18116"],"award-info":[{"award-number":["CA-18116"]}]},{"name":"Swedish Research Council","award":["EJPRD20-135"],"award-info":[{"award-number":["EJPRD20-135"]}]},{"name":"Swedish Research Council","award":["2020-00798"],"award-info":[{"award-number":["2020-00798"]}]},{"name":"Swedish Research Council","award":["CA-18116"],"award-info":[{"award-number":["CA-18116"]}]},{"name":"European Union Cooperation on Science and Technology COST Action","award":["EJPRD20-135"],"award-info":[{"award-number":["EJPRD20-135"]}]},{"name":"European Union Cooperation on Science and Technology COST Action","award":["2020-00798"],"award-info":[{"award-number":["2020-00798"]}]},{"name":"European Union Cooperation on Science and Technology COST Action","award":["CA-18116"],"award-info":[{"award-number":["CA-18116"]}]},{"name":"ANIRIDIA-NET","award":["EJPRD20-135"],"award-info":[{"award-number":["EJPRD20-135"]}]},{"name":"ANIRIDIA-NET","award":["2020-00798"],"award-info":[{"award-number":["2020-00798"]}]},{"name":"ANIRIDIA-NET","award":["CA-18116"],"award-info":[{"award-number":["CA-18116"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells12040617","type":"journal-article","created":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T03:37:24Z","timestamp":1676432244000},"page":"617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["MAPK Pathways in Ocular Pathophysiology: Potential Therapeutic Drugs and Challenges"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3192-3708","authenticated-orcid":false,"given":"Petros","family":"Moustardas","sequence":"first","affiliation":[{"name":"Division of Ophthalmology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4019-5418","authenticated-orcid":false,"given":"Daniel","family":"Aberdam","sequence":"additional","affiliation":[{"name":"INSERM U1138, Centre des Cordeliers, 75270 Paris, France"},{"name":"Universit\u00e9 de Paris Cit\u00e9, 75014 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1079-4361","authenticated-orcid":false,"given":"Neil","family":"Lagali","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology, Department of Biomedical and Clinical Sciences, Link\u00f6ping University, 58185 Link\u00f6ping, Sweden"},{"name":"Department of Ophthalmology, S\u00f8rlandet Hospital Arendal, 4838 Arendal, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1002\/pro.2374","article-title":"Molecular basis of MAP kinase regulation","volume":"22","author":"Peti","year":"2013","journal-title":"Protein Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1128\/MMBR.00031-10","article-title":"Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases","volume":"75","author":"Cargnello","year":"2011","journal-title":"Microbiol. 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