Altered miRNA Expression in Canine Retinas During Normal Development and in Models of Retinal Degeneration

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dc.contributor.authorGenini, Sem
dc.contributor.authorGuziewicz, Karina E
dc.contributor.authorBeltran, William A
dc.contributor.authorGenini, Sem
dc.contributor.authorGuziewicz, Karina E
dc.contributor.authorAguirre, Gustavo D
dc.contributor.authorBeltran, William A
dc.date2023-05-17T19:54:59.000
dc.date.accessioned2023-05-23T04:44:55Z
dc.date.available2023-05-23T04:44:55Z
dc.date.issued2014-01-01
dc.date.submitted2018-04-05T14:00:31-07:00
dc.description.abstractBackground Although more than 246 loci/genes are associated with inherited retinal diseases, the mechanistic events that link genetic mutations to photoreceptor cell death are poorly understood. miRNAs play a relevant role during retinal development and disease. Thus, as a first step in characterizing miRNA involvement during disease expression and progression, we examined miRNAs expression changes in normal retinal development and in four canine models of retinal degenerative disease. Results The initial microarray analysis showed that 50 miRNAs were differentially expressed (DE) early (3 vs. 7 wks) in normal retina development, while only 2 were DE between 7 and 16 wks, when the dog retina is fully mature. miRNA expression profiles were similar between dogs affected with xlpra2, an early-onset retinal disease caused by a microdeletion in RPGRORF15, and normal dogs early in development (3 wks) and at the peak of photoreceptor death (7 wks), when only 2 miRNAs were DE. However, the expression varied much more markedly during the chronic cell death stage at 16 wks (118 up-/55 down-regulated miRNAs). Functional analyses indicated that these DE miRNAs are associated with an increased inflammatory response, as well as cell death/survival. qRT-PCR of selected apoptosis-related miRNAs (“apoptomirs”) confirmed the microarray results in xlpra2, and extended the analysis to the early-onset retinal diseases rcd1 (PDE6B-mutation) and erd (STK38L-mutation), as well as the slowly progressing prcd (PRCD-mutation). The results showed up-regulation of anti-apoptotic (miR-9, -19a, -20, -21, -29b, -146a, -155, -221) and down-regulation of pro-apoptotic (miR-122, -129) apoptomirs in the early-onset diseases and, with few exceptions, also in the prcd-mutants. Conclusions Our results suggest that apoptomirs might be expressed by diseased retinas in an attempt to counteract the degenerative process. The pattern of expression in diseased retinas mirrored the morphology and cell death kinetics previously described for these diseases. This study suggests that common miRNA regulatory mechanisms may be involved in retinal degeneration processes and provides attractive opportunities for the development of novel miRNA-based therapies to delay the progression of the degenerative process.
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/48918
dc.legacy.articleid1155
dc.legacy.fields10.1186/1471-2164-15-172
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=1155&context=vet_papers&unstamped=1
dc.rights<p>© 2014 Genini et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</p>
dc.source.issue155
dc.source.issue172
dc.source.journalDepartmental Papers (Vet)
dc.source.journaltitleBMC Genomics
dc.source.peerreviewedtrue
dc.source.statuspublished
dc.source.volume15
dc.subject.otherApoptomirs
dc.subject.otherCanine models
dc.subject.othererd
dc.subject.otherInherited retinal disorders
dc.subject.otherMicroarray
dc.subject.othermiRNA expression profiles
dc.subject.otherprcd
dc.subject.otherqRT-PCR
dc.subject.otherrcd1
dc.subject.otherxlpra2
dc.subject.otherMedicine and Health Sciences
dc.subject.otherVeterinary Medicine
dc.titleAltered miRNA Expression in Canine Retinas During Normal Development and in Models of Retinal Degeneration
dc.typeArticle
digcom.contributor.authorisAuthorOfPublication|email:geninis@vet.upenn.edu|institution:University of Pennsylvania|Genini, Sem
digcom.contributor.authorisAuthorOfPublication|email:karinag@vet.upenn.edu|institution:University of Pennsylvania|Guziewicz, Karina E
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/155
digcom.identifier.contextkey11913309
digcom.identifier.submissionpathvet_papers/155
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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