---
_id: '557'
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.
article_processing_charge: No
author:
- first_name: Robert
  full_name: Nickells, Robert
  last_name: Nickells
- first_name: Heather
  full_name: Schmitt, Heather
  last_name: Schmitt
- first_name: Margaret E
  full_name: Maes, Margaret E
  id: 3838F452-F248-11E8-B48F-1D18A9856A87
  last_name: Maes
  orcid: 0000-0001-9642-1085
- first_name: Cassandra
  full_name: Schlamp, Cassandra
  last_name: Schlamp
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>
  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>.
  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.
  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>.
  short: R. Nickells, H. Schmitt, M.E. Maes, C. Schlamp, Investigative Ophthalmology
    and Visual Science 58 (2017) 6091–6104.
date_created: 2018-12-11T11:47:10Z
date_published: 2017-12-14T00:00:00Z
date_updated: 2023-10-10T14:06:18Z
day: '14'
ddc:
- '576'
department:
- _id: SaSi
doi: 10.1167/iovs.17-22634
file:
- access_level: open_access
  checksum: d7a7b6f1fa9211a04e5e65634a0265d9
  content_type: application/pdf
  creator: system
  date_created: 2018-12-12T10:17:53Z
  date_updated: 2020-07-14T12:47:04Z
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  file_name: IST-2018-920-v1+1_i1552-5783-58-14-6091.pdf
  file_size: 2955559
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file_date_updated: 2020-07-14T12:47:04Z
has_accepted_license: '1'
intvolume: '        58'
issue: '14'
language:
- iso: eng
month: '12'
oa: 1
oa_version: Published Version
page: 6091 - 6104
publication: Investigative Ophthalmology and Visual Science
publication_identifier:
  issn:
  - '01460404'
publication_status: published
publisher: Association for Research in Vision and Ophthalmology
publist_id: '7254'
pubrep_id: '920'
quality_controlled: '1'
scopus_import: '1'
status: public
title: AAV2 mediated transduction of the mouse retina after optic nerve injury
tmp:
  image: /images/cc_by_nc_nd.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
    (CC BY-NC-ND 4.0)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 58
year: '2017'
...