Identifier |
20230314_nanos_sciplatform2_04 |
Title |
Epigenetic Reprogramming- A Novel Gene Therapy to Rejuvenate Injury-Induced Dysfunction of Retinal Ganglion Cells in Optic Neuropathies |
Creator |
Drenushe Krasniqi; Madhura Shah; Margarete Karg; Yuancheng Lu; David Sinclair; Bruce Ksander; Joseph Rizzo |
Affiliation |
(DK) (MK) (BK) Schepens Eye Research Institute/ Mass. Eye and Ear; (MS) Massachusetts Eye and Ear; (YL) Sinclair Lab, Harvard Medical School; (DS) Harvard Medical School; (JR) Massachussets Eye and Ear |
Subject |
Optic Nerve Trauma and Treatment; Optic Neuropathy |
Description |
NAION (Non-Arteritic Anterior Ischemic Optic Neuropathy) and glaucoma are optic neuropathies with different pathophysiology but a common endpoint, the apoptosis of retinal ganglion cells (RGCs). Our recently published studies indicate ganglion cell injury triggers epigenetic changes consistent with those associated with aging (ie the 'epigenetic clock'). We developed a novel gene therapy called 'epigenetic reprogramming' using the AAV2 (adeno-associated virus) vector to transiently express three reprogramming genes [OSK: Oct4, Sox2, Klf4)] that remove epigenetic signals associated with aging. Reprogramming RGCs in aging mice and mice with microbead-induced elevated pressure glaucoma restored lost visual function as measured by pERG and OMR (Optomotor Reflex) and coincided with restoring a 'young' transcriptome and methylome in RGCs. Importantly, delivery and activation of OSK reprogramming genes occurred after loss of RGC function had already occurred. In the current study, we determined the duration of restored visual function and the long-term safety of OSK gene therapy. |
Date |
2023-03 |
Language |
eng |
Format |
application/pdf |
Type |
Text |
Source |
2023 North American Neuro-Ophthalmology Society Annual Meeting |
Relation is Part of |
NANOS Annual Meeting 2023: Scientific Platform Session II |
Collection |
Neuro-Ophthalmology Virtual Education Library: NANOS Annual Meeting Collection: https://novel.utah.edu/collection/nanos-annual-meeting-collection/ |
Publisher |
North American Neuro-Ophthalmology Society |
Holding Institution |
Spencer S. Eccles Health Sciences Library, University of Utah |
Rights Management |
Copyright 2023. For further information regarding the rights to this collection, please visit: https://NOVEL.utah.edu/about/copyright |
ARK |
ark:/87278/s6fwe0by |
Context URL |
The NANOS Annual Meeting Neuro-Ophthalmology Collection: https://novel.utah.edu/collection/NAM/toc/ |
Setname |
ehsl_novel_nam |
ID |
2309960 |
Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6fwe0by |