{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T19:26:43Z","timestamp":1782502003727,"version":"3.54.5"},"reference-count":55,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T00:00:00Z","timestamp":1645920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BR 4957\/3-1"],"award-info":[{"award-number":["BR 4957\/3-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["NE 2372\/1-1"],"award-info":[{"award-number":["NE 2372\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"PRO RETINA Deutschland e.V.","award":["B.M.B., S.I.S"],"award-info":[{"award-number":["B.M.B., S.I.S"]}]},{"name":"Jackst\u00e4dt Foundation","award":["B.M.B"],"award-info":[{"award-number":["B.M.B"]}]},{"name":"Helmut Ecker Foundation","award":["B.M.B."],"award-info":[{"award-number":["B.M.B."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Transforming growth factor \u03b2 (TGF\u03b2) signaling has manifold functions such as regulation of cell growth, differentiation, migration, and apoptosis. Moreover, there is increasing evidence that it also acts in a neuroprotective manner. We recently showed that TGF\u03b2 receptor type 2 (Tgfbr2) is upregulated in retinal neurons and M\u00fcller cells during retinal degeneration. In this study we investigated if this upregulation of TGF\u03b2 signaling would have functional consequences in protecting retinal neurons. To this end, we analyzed the impact of TGF\u03b2 signaling on photoreceptor viability using mice with cell type-specific deletion of Tgfbr2 in retinal neurons and M\u00fcller cells (Tgfbr2\u0394OC) in combination with a genetic model of photoreceptor degeneration (VPP). We examined retinal morphology and the degree of photoreceptor degeneration, as well as alterations of the retinal transcriptome. In summary, retinal morphology was not altered due to TGF\u03b2 signaling deficiency. In contrast, VPP-induced photoreceptor degeneration was drastically exacerbated in double mutant mice (Tgfbr2\u0394OC; VPP) by induction of pro-apoptotic genes and dysregulation of the MAP kinase pathway. Therefore, TGF\u03b2 signaling in retinal neurons and M\u00fcller cells exhibits a neuroprotective effect and might pose promising therapeutic options to attenuate photoreceptor degeneration in humans.<\/jats:p>","DOI":"10.3390\/ijms23052626","type":"journal-article","created":{"date-parts":[[2022,2,27]],"date-time":"2022-02-27T20:47:17Z","timestamp":1645994837000},"page":"2626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Deficiency in Retinal TGF\u03b2 Signaling Aggravates Neurodegeneration by Modulating Pro-Apoptotic and MAP Kinase Pathways"],"prefix":"10.3390","volume":"23","author":[{"given":"Christina B.","family":"Bielmeier","sequence":"first","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Julius-Maximilians-University Wuerzburg, 97070 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina I.","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Institute of Human Anatomy and Embryology, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolai","family":"Kleefeldt","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Wuerzburg, 97070 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9811-2160","authenticated-orcid":false,"given":"Stefaniya K.","family":"Boneva","sequence":"additional","affiliation":[{"name":"Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Schlecht","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Julius-Maximilians-University Wuerzburg, 97070 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Vallon","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Julius-Maximilians-University Wuerzburg, 97070 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernst R.","family":"Tamm","sequence":"additional","affiliation":[{"name":"Institute of Human Anatomy and Embryology, University of Regensburg, 93053 Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jost","family":"Hillenkamp","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Hospital Wuerzburg, 97070 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00fcleyman","family":"Erg\u00fcn","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Julius-Maximilians-University Wuerzburg, 97070 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2389-5236","authenticated-orcid":false,"given":"Andreas","family":"Neueder","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Ulm, 89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara M.","family":"Braunger","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology, Julius-Maximilians-University Wuerzburg, 97070 Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.ophtha.2003.05.010","article-title":"Prevalence and causes of visual impairment and blindness among 9980 Scandinavian adults: The Copenhagen City Eye Study","volume":"111","author":"Buch","year":"2004","journal-title":"Ophthalmology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1093\/emboj\/21.5.857","article-title":"On the genetics of retinitis pigmentosa and on mutation-independent approaches to therapeutic intervention","volume":"21","author":"Farrar","year":"2002","journal-title":"EMBO J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1016\/S0140-6736(06)69740-7","article-title":"Retinitis pigmentosa","volume":"368","author":"Hartong","year":"2006","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1080\/15476286.2016.1191735","article-title":"Mutations in spliceosomal proteins and retina degeneration","volume":"14","author":"Ruzickova","year":"2017","journal-title":"RNA Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.1056\/NEJMra062326","article-title":"Age-related macular degeneration","volume":"355","year":"2006","journal-title":"N. 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