{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T23:38:12Z","timestamp":1785368292538,"version":"3.55.0"},"reference-count":42,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T00:00:00Z","timestamp":1628208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY019311"],"award-info":[{"award-number":["EY019311"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY030096"],"award-info":[{"award-number":["EY030096"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30 EY003039"],"award-info":[{"award-number":["P30 EY003039"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["Challenge Award (UTHSC)"],"award-info":[{"award-number":["Challenge Award (UTHSC)"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University of Tennessee Research Foundation Technology Maturation Grant","award":["UTRF to TJH and MMJ"],"award-info":[{"award-number":["UTRF to TJH and MMJ"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Retinitis pigmentosa (RP) is a hereditary disease of the retina that results in complete blindness. Currently, there are very few treatments for the disease and those that exist work only for the recessively inherited forms. To better understand the pathogenesis of RP, multiple mouse models have been generated bearing mutations found in human patients including the human Q344X rhodopsin knock-in mouse. In recent years, the immune system was shown to play an increasingly important role in RP degeneration. By way of electroretinography, optical coherence tomography, funduscopy, fluorescein angiography, and fluorescent immunohistochemistry, we show degenerative and vascular phenotypes, microglial activation, photoreceptor phagocytosis, and upregulation of proinflammatory pathway proteins in the retinas of the human Q344X rhodopsin knock-in mouse. We also show that an FDA-approved pharmacological agent indicated for the treatment of rheumatoid arthritis is able to halt activation of pro-inflammatory signaling in cultured retinal cells, setting the stage for pre-clinical trials using these mice to inhibit proinflammatory signaling in an attempt to preserve vision. We conclude from this work that pro- and autoinflammatory upregulation likely act to enhance the progression of the degenerative phenotype of rhodopsin Q344X-mediated RP and that inhibition of these pathways may lead to longer-lasting vision in not only the Q344X rhodopsin knock-in mice, but humans as well.<\/jats:p>","DOI":"10.3390\/biom11081163","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T08:01:42Z","timestamp":1628236902000},"page":"1163","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Proinflammatory Pathways Are Activated in the Human Q344X Rhodopsin Knock-In Mouse Model of Retinitis Pigmentosa"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2119-521X","authenticated-orcid":false,"given":"T.J.","family":"Hollingsworth","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Hamilton Eye Institute, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith G.","family":"Hubbard","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailey J.","family":"Levi","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"White","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hamilton Eye Institute, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hamilton Eye Institute, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raven","family":"Simpson","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hamilton Eye Institute, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4021-3559","authenticated-orcid":false,"given":"Monica M.","family":"Jablonski","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Hamilton Eye Institute, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1857-6633","authenticated-orcid":false,"given":"Alecia K.","family":"Gross","sequence":"additional","affiliation":[{"name":"Department of Neurobiology, Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/B978-0-12-394304-0.00006-3","article-title":"Defective Trafficking of Rhodopsin and Its Role in Retinal Degenerations","volume":"293","author":"Hollingsworth","year":"2012","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"29047","DOI":"10.1074\/jbc.M113.495184","article-title":"The Severe Autosomal Dominant Retinitis Pigmentosa Rhodopsin Mutant Ter349Glu Mislocalizes and Induces Rapid Rod Cell Death","volume":"288","author":"Hollingsworth","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Hollingsworth, T.J., and Gross, A.K. (2020). 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