Prostaglandin-based rAAV-mediated glaucoma gene therapy in Brown Norway rats. Commun Biol 2022 Nov 03;5(1):1169
Date
11/05/2022Pubmed ID
36329259Pubmed Central ID
PMC9633612DOI
10.1038/s42003-022-04134-wScopus ID
2-s2.0-85141145849 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
Prostaglandin analogs are first-line treatments for open angle glaucoma and while effective at lowering intraocular pressure, they are undermined by patient non-compliance, causing atrophy of the optic nerve and severe visual impairment. Herein, we evaluate the safety and efficacy of a recombinant adeno-associated viral vector-mediated gene therapy aimed at permanently lowering intraocular pressure through de novo biosynthesis of prostaglandin F2α 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 major 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.
Author List
Chern KJ, Nettesheim ER, Reid CA, Li NW, Marcoe GJ, Lipinski DMAuthor
Daniel M. Lipinski PhD Associate Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsGenetic Therapy
Glaucoma
Glaucoma, Open-Angle
Ocular Hypertension
Prostaglandins
Rats
