[{"year":"2021","date_created":"2021-09-12T22:01:23Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_updated":"2023-08-14T06:35:17Z","volume":62,"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"date_published":"2021-08-16T00:00:00Z","ddc":["570"],"abstract":[{"text":"Inhibition or targeted deletion of histone deacetylase 3 (HDAC3) is neuroprotective in a variety neurodegenerative conditions, including retinal ganglion cells (RGCs) after acute optic nerve damage. Consistent with this, induced HDAC3 expression in cultured cells shows selective toxicity to neurons. Despite an established role for HDAC3 in neuronal pathology, little is known regarding the mechanism of this pathology.","lang":"eng"}],"doi":"10.1167/IOVS.62.10.14","publication_status":"published","department":[{"_id":"SaSi"}],"external_id":{"isi":["000695230000014"],"pmid":["34398198"]},"file":[{"access_level":"open_access","file_name":"2021_IOVS_Schmitt.pdf","file_size":19707796,"date_updated":"2022-05-13T07:40:15Z","creator":"dernst","date_created":"2022-05-13T07:40:15Z","content_type":"application/pdf","success":1,"checksum":"c430967746f653aa1ae84ee617f62b73","file_id":"11369","relation":"main_file"}],"intvolume":"        62","publication":"Investigative Ophthalmology and Visual Science","file_date_updated":"2022-05-13T07:40:15Z","quality_controlled":"1","month":"08","publisher":"Association for Research in Vision and Ophthalmology","publication_identifier":{"eissn":["1552-5783"],"issn":["0146-0404"]},"article_number":"14","day":"16","type":"journal_article","status":"public","oa":1,"language":[{"iso":"eng"}],"author":[{"first_name":"Heather M.","last_name":"Schmitt","full_name":"Schmitt, Heather M."},{"first_name":"Rachel L.","last_name":"Fehrman","full_name":"Fehrman, Rachel L."},{"id":"3838F452-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9642-1085","full_name":"Maes, Margaret E","last_name":"Maes","first_name":"Margaret E"},{"full_name":"Yang, Huan","last_name":"Yang","first_name":"Huan"},{"first_name":"Lian Wang","full_name":"Guo, Lian Wang","last_name":"Guo"},{"first_name":"Cassandra L.","full_name":"Schlamp, Cassandra L.","last_name":"Schlamp"},{"last_name":"Pelzel","full_name":"Pelzel, Heather R.","first_name":"Heather R."},{"last_name":"Nickells","full_name":"Nickells, Robert W.","first_name":"Robert W."}],"article_processing_charge":"Yes","article_type":"original","issue":"10","_id":"10000","scopus_import":"1","oa_version":"Published Version","acknowledgement":"The authors thank Joel Dietz for maintaining the mice used in this study, Satoshi Kinoshita and the Translational Research Initiative in Pathology Laboratory at the University of Wisconsin-Madison for cutting retinal sections analyzed in this study, and Mark Banghart for statistical review of the data analysis. Supported by National Eye Institute Grants R01 EY012223 (RWN), R01 EY030123 (RWN), R01 EY029809 (LWG), R01 EY029809 (LWG) and a Vision Research CORE grant P30 EY016665, NRSA grant T32 GM081061, by an unrestricted research grant from Research to Prevent Blindness, Inc., and by a University of Wisconsin-Madison Vilas Life Cycle award and the Frederick A. Davis Research Chair (RWN). ","isi":1,"title":"Increased susceptibility and intrinsic apoptotic signaling in neurons by induced HDAC3 expression","citation":{"short":"H.M. Schmitt, R.L. Fehrman, M.E. Maes, H. Yang, L.W. Guo, C.L. Schlamp, H.R. Pelzel, R.W. Nickells, Investigative Ophthalmology and Visual Science 62 (2021).","ama":"Schmitt HM, Fehrman RL, Maes ME, et al. Increased susceptibility and intrinsic apoptotic signaling in neurons by induced HDAC3 expression. <i>Investigative Ophthalmology and Visual Science</i>. 2021;62(10). doi:<a href=\"https://doi.org/10.1167/IOVS.62.10.14\">10.1167/IOVS.62.10.14</a>","ieee":"H. M. Schmitt <i>et al.</i>, “Increased susceptibility and intrinsic apoptotic signaling in neurons by induced HDAC3 expression,” <i>Investigative Ophthalmology and Visual Science</i>, vol. 62, no. 10. Association for Research in Vision and Ophthalmology, 2021.","apa":"Schmitt, H. M., Fehrman, R. L., Maes, M. E., Yang, H., Guo, L. W., Schlamp, C. L., … Nickells, R. W. (2021). Increased susceptibility and intrinsic apoptotic signaling in neurons by induced HDAC3 expression. <i>Investigative Ophthalmology and Visual Science</i>. Association for Research in Vision and Ophthalmology. <a href=\"https://doi.org/10.1167/IOVS.62.10.14\">https://doi.org/10.1167/IOVS.62.10.14</a>","ista":"Schmitt HM, Fehrman RL, Maes ME, Yang H, Guo LW, Schlamp CL, Pelzel HR, Nickells RW. 2021. Increased susceptibility and intrinsic apoptotic signaling in neurons by induced HDAC3 expression. Investigative Ophthalmology and Visual Science. 62(10), 14.","chicago":"Schmitt, Heather M., Rachel L. Fehrman, Margaret E Maes, Huan Yang, Lian Wang Guo, Cassandra L. Schlamp, Heather R. Pelzel, and Robert W. Nickells. “Increased Susceptibility and Intrinsic Apoptotic Signaling in Neurons by Induced HDAC3 Expression.” <i>Investigative Ophthalmology and Visual Science</i>. Association for Research in Vision and Ophthalmology, 2021. <a href=\"https://doi.org/10.1167/IOVS.62.10.14\">https://doi.org/10.1167/IOVS.62.10.14</a>.","mla":"Schmitt, Heather M., et al. “Increased Susceptibility and Intrinsic Apoptotic Signaling in Neurons by Induced HDAC3 Expression.” <i>Investigative Ophthalmology and Visual Science</i>, vol. 62, no. 10, 14, Association for Research in Vision and Ophthalmology, 2021, doi:<a href=\"https://doi.org/10.1167/IOVS.62.10.14\">10.1167/IOVS.62.10.14</a>."},"has_accepted_license":"1","pmid":1},{"page":"6091 - 6104","status":"public","day":"14","type":"journal_article","publication_identifier":{"issn":["0146-0404"]},"publisher":"Association for Research in Vision and Ophthalmology","month":"12","quality_controlled":"1","issue":"14","_id":"557","article_processing_charge":"No","author":[{"first_name":"Robert","last_name":"Nickells","full_name":"Nickells, Robert"},{"last_name":"Schmitt","full_name":"Schmitt, Heather","first_name":"Heather"},{"first_name":"Margaret E","id":"3838F452-F248-11E8-B48F-1D18A9856A87","full_name":"Maes, Margaret E","orcid":"0000-0001-9642-1085","last_name":"Maes"},{"last_name":"Schlamp","full_name":"Schlamp, Cassandra","first_name":"Cassandra"}],"oa":1,"language":[{"iso":"eng"}],"title":"AAV2 mediated transduction of the mouse retina after optic nerve injury","isi":1,"scopus_import":"1","oa_version":"Published Version","has_accepted_license":"1","pubrep_id":"920","citation":{"ama":"Nickells R, Schmitt H, Maes ME, Schlamp C. AAV2 mediated transduction of the mouse retina after optic nerve injury. <i>Investigative Ophthalmology and Visual Science</i>. 2017;58(14):6091-6104. doi:<a href=\"https://doi.org/10.1167/iovs.17-22634\">10.1167/iovs.17-22634</a>","short":"R. Nickells, H. Schmitt, M.E. Maes, C. Schlamp, Investigative Ophthalmology and Visual Science 58 (2017) 6091–6104.","ieee":"R. Nickells, H. Schmitt, M. E. Maes, and C. Schlamp, “AAV2 mediated transduction of the mouse retina after optic nerve injury,” <i>Investigative Ophthalmology and Visual Science</i>, vol. 58, no. 14. Association for Research in Vision and Ophthalmology, pp. 6091–6104, 2017.","ista":"Nickells R, Schmitt H, Maes ME, Schlamp C. 2017. AAV2 mediated transduction of the mouse retina after optic nerve injury. Investigative Ophthalmology and Visual Science. 58(14), 6091–6104.","apa":"Nickells, R., Schmitt, H., Maes, M. E., &#38; Schlamp, C. (2017). AAV2 mediated transduction of the mouse retina after optic nerve injury. <i>Investigative Ophthalmology and Visual Science</i>. Association for Research in Vision and Ophthalmology. <a href=\"https://doi.org/10.1167/iovs.17-22634\">https://doi.org/10.1167/iovs.17-22634</a>","chicago":"Nickells, Robert, Heather Schmitt, Margaret E Maes, and Cassandra Schlamp. “AAV2 Mediated Transduction of the Mouse Retina after Optic Nerve Injury.” <i>Investigative Ophthalmology and Visual Science</i>. Association for Research in Vision and Ophthalmology, 2017. <a href=\"https://doi.org/10.1167/iovs.17-22634\">https://doi.org/10.1167/iovs.17-22634</a>.","mla":"Nickells, Robert, et al. “AAV2 Mediated Transduction of the Mouse Retina after Optic Nerve Injury.” <i>Investigative Ophthalmology and Visual Science</i>, vol. 58, no. 14, Association for Research in Vision and Ophthalmology, 2017, pp. 6091–104, doi:<a href=\"https://doi.org/10.1167/iovs.17-22634\">10.1167/iovs.17-22634</a>."},"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","date_created":"2018-12-11T11:47:10Z","publist_id":"7254","year":"2017","date_published":"2017-12-14T00:00:00Z","ddc":["576"],"date_updated":"2026-04-16T09:58:51Z","tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"volume":58,"department":[{"_id":"SaSi"}],"external_id":{"isi":["000426781300012"]},"publication_status":"published","doi":"10.1167/iovs.17-22634","abstract":[{"lang":"eng","text":"PURPOSE. Gene therapy of retinal ganglion cells (RGCs) has promise as a powerful therapeutic for the rescue and regeneration of these cells after optic nerve damage. However, early after damage, RGCs undergo atrophic changes, including gene silencing. It is not known if these changes will deleteriously affect transduction and transgene expression, or if the therapeutic protein can influence reactivation of the endogenous genome. METHODS. Double-transgenic mice carrying a Rosa26-(LoxP)-tdTomato reporter, and a mutant allele for the proapoptotic Bax gene were reared. The Bax mutant blocks apoptosis, but RGCs still exhibit nuclear atrophy and gene silencing. At times ranging from 1 hour to 4 weeks after optic nerve crush (ONC), eyes received an intravitreal injection of AAV2 virus carrying the Cre recombinase. Successful transduction was monitored by expression of the tdTomato reporter. Immunostaining was used to localize tdTomato expression in select cell types. RESULTS. Successful transduction of RGCs was achieved at all time points after ONC using AAV2 expressing Cre from the phosphoglycerate kinase (Pgk) promoter, but not the CMV promoter. ONC promoted an increase in the transduction of cell types in the inner nuclear layer, including Müller cells and rod bipolar neurons. There was minimal evidence of transduction of amacrine cells and astrocytes in the inner retina or optic nerve. CONCLUSIONS. Damaged RGCs can be transduced and at least some endogenous genes can be subsequently activated. Optic nerve damage may change retinal architecture to allow greater penetration of an AAV2 virus to transduce several additional cell types in the inner nuclear layer."}],"file_date_updated":"2020-07-14T12:47:04Z","publication":"Investigative Ophthalmology and Visual Science","intvolume":"        58","file":[{"creator":"system","access_level":"open_access","date_updated":"2020-07-14T12:47:04Z","file_size":2955559,"file_name":"IST-2018-920-v1+1_i1552-5783-58-14-6091.pdf","file_id":"5311","checksum":"d7a7b6f1fa9211a04e5e65634a0265d9","relation":"main_file","date_created":"2018-12-12T10:17:53Z","content_type":"application/pdf"}]}]