Transient Photoreceptor Deconstruction by CNTF Enhances rAAV-Mediated Cone Functional Rescue in Late Stage CNGB3-Achromatopsia

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dc.contributor.authorKomáromy, András M
dc.contributor.authorAguirre, Gustavo D
dc.contributor.authorKomáromy, András M
dc.contributor.authorAguirre, Gustavo D
dc.contributor.authorRowlan, Jessica S
dc.contributor.authorParton Corr, Amanda T
dc.contributor.authorReinstein, Shelby L
dc.contributor.authorBoye, Sanford L
dc.contributor.authorCooper, Ann E
dc.contributor.authorGonzalez, Amaliris
dc.contributor.authorBeltran, William A
dc.contributor.authorWen, Rong
dc.contributor.authorHauswirth, William W
dc.contributor.authorBeltran, William A
dc.date2023-05-17T19:56:29.000
dc.date.accessioned2023-05-23T04:45:01Z
dc.date.available2023-05-23T04:45:01Z
dc.date.issued2013-06-01
dc.date.submitted2018-04-19T14:12:43-07:00
dc.description.abstractAchromatopsia is a genetic disorder of cones, and one of the most common forms is a channelopathy caused by mutations in the β-subunit, CNGB3, of the cone cyclic nucleotide-gated (CNG) channel. Recombinant adeno-associated virus of serotype 5 (rAAV5)-mediated gene transfer of human CNGB3 cDNA to mutant dog cones results in functional and structural rescue in dogs <0.5 years of age, but treatment is minimally effective in dogs >1 year. We now test a new therapeutic concept by combining gene therapy with the administration of ciliary neurotrophic factor (CNTF). Intravitreal CNTF causes transient dedifferentiation of photoreceptors, a process called deconstruction, whereby visual cells become immature with short outer segments, and decreased retinal function and gene expression that subsequently return to normal. Cone function was successfully rescued in all mutant dogs treated between 14 and 42 months of age with this strategy. CNTF-mediated deconstruction and regeneration of the photoreceptor outer segments prepares the mutant cones optimally for gene augmentation therapy.
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/48929
dc.legacy.articleid1173
dc.legacy.fields10.1038/mt.2013.50
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=1173&amp;context=vet_papers&amp;unstamped=1
dc.rights<p>This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.</p>
dc.source.beginpage1131
dc.source.endpage1141
dc.source.issue165
dc.source.issue6
dc.source.journalDepartmental Papers (Vet)
dc.source.journaltitleMolecular Therapy
dc.source.peerreviewedtrue
dc.source.statuspublished
dc.source.volume21
dc.subject.otherMedicine and Health Sciences
dc.subject.otherVeterinary Medicine
dc.titleTransient Photoreceptor Deconstruction by CNTF Enhances rAAV-Mediated Cone Functional Rescue in Late Stage CNGB3-Achromatopsia
dc.typeArticle
digcom.contributor.authorisAuthorOfPublication|email:komaromy@vet.upenn.edu|institution:University of Pennsylvania|Komáromy, András M
digcom.contributor.authorRowlan, Jessica S
digcom.contributor.authorParton Corr, Amanda T
digcom.contributor.authorReinstein, Shelby L
digcom.contributor.authorBoye, Sanford L
digcom.contributor.authorCooper, Ann E
digcom.contributor.authorGonzalez, Amaliris
digcom.contributor.authorLevy, Britt
digcom.contributor.authorWen, Rong
digcom.contributor.authorHauswirth, William W
digcom.contributor.authorisAuthorOfPublication|email:wbeltran@vet.upenn.edu|institution:University of Pennsylvania|Beltran, William A
digcom.contributor.authorisAuthorOfPublication|email:gda@vet.upenn.edu|institution:University of Pennsylvania|Aguirre, Gustavo D
digcom.identifiervet_papers/165
digcom.identifier.contextkey11993777
digcom.identifier.submissionpathvet_papers/165
digcom.typearticle
dspace.entity.typePublication
person.identifier.orcid0000-0002-5228-256X
person.identifier.orcid0000-0002-5228-256X
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upenn.schoolDepartmentCenterDepartmental Papers (Vet)
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