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Herein, we evaluate the safety and efficacy of a recombinant adeno-associated viral vector-mediated gene therapy aimed at permanently lowering intraocular pressure through <jats:italic>de novo<\/jats:italic> biosynthesis of prostaglandin F2\u03b1 within the anterior chamber. This study demonstrated a dose dependent reduction in intraocular pressure in normotensive Brown Norway rats maintained over 12-months. Crucially, therapy could be temporarily halted through off-type riboswitch activation, reverting intraocular pressure to normal. Longitudinal multimodal imaging, electrophysiology, and post-mortem histology revealed the therapy was well tolerated at low and medium doses, with no\u00a0major adverse effects to anterior chamber health, offering a promising alternative to current treatment strategies leading to clinically relevant reductions in intraocular pressure without the need for adherence to a daily treatment regimen.<\/jats:p>","DOI":"10.1038\/s42003-022-04134-w","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T06:04:43Z","timestamp":1667455483000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Prostaglandin-based rAAV-mediated glaucoma gene therapy in Brown Norway rats"],"prefix":"10.1038","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2461-7051","authenticated-orcid":false,"given":"Kristina J.","family":"Chern","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8581-1205","authenticated-orcid":false,"given":"Emily R.","family":"Nettesheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher A.","family":"Reid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan W.","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin J.","family":"Marcoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7828-614X","authenticated-orcid":false,"given":"Daniel M.","family":"Lipinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,3]]},"reference":[{"key":"4134_CR1","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1136\/bjo.2005.081224","volume":"90","author":"H Quigley","year":"2006","unstructured":"Quigley, H. & Broman, A. 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