September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Gene Expression Changes and Pathway Analysis of the Degenerating Murine Retina in Response to Intravitreal Administration of Human CD34+ Stem Cells
Author Affiliations & Notes
  • Zeljka Smit-McBride
    Ophthalmology, Univ of California, Davis Sch of Med, Davis, California, United States
  • Elad Moisseiev
    Ophthalmology, Univ of California, Davis Sch of Med, Davis, California, United States
  • Whitney Cary
    Stem Cell Program, Institute for Regenerative Cures, UC Davis, Sacramento, California, United States
  • Geralyn Annett
    Stem Cell Program, Institute for Regenerative Cures, UC Davis, Sacramento, California, United States
  • Jan Nolta
    Stem Cell Program, Institute for Regenerative Cures, UC Davis, Sacramento, California, United States
  • Susanna S Park
    Ophthalmology, Univ of California, Davis Sch of Med, Davis, California, United States
  • Footnotes
    Commercial Relationships   Zeljka Smit-McBride, None; Elad Moisseiev, None; Whitney Cary, None; Geralyn Annett, None; Jan Nolta, None; Susanna Park, None
  • Footnotes
    Support  Barr Foundation at UC Davis Dept of Ophthalmology (to ZSM), Foundation Fighting Blindness
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4792. doi:
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      Zeljka Smit-McBride, Elad Moisseiev, Whitney Cary, Geralyn Annett, Jan Nolta, Susanna S Park; Gene Expression Changes and Pathway Analysis of the Degenerating Murine Retina in Response to Intravitreal Administration of Human CD34+ Stem Cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4792.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To characterize the gene expression changes and affected signaling pathways in the degenerating mouse retina in response to intravitreal injection of human CD34+ stem cells.

Methods : C3H/HeJrd1/rd1 mice, systemically immunosuppressed, were injected intravitrealy with PBS (n=16) or human bone marrow CD34+ cells (n=16). Animals were euthanized at weeks 1 and 4 post-injection, eyes harvested, retina dissected and preserved in RNALater. Total RNA was isolated using Qiagen miRNeasy kit. Labeled probes were hybridized to the Affymetrix Mouse Transcriptome Assay 1.0 (MTA1) GeneChip microarrays. Raw microarray .cel files were analyzed using Affymetrix Expression Console followed by Transcriptome Analysis Console 3.0, to identify differentially expressed genes. Ingenuity Pathway Analysis and WikiPathways were used for biologically relevant changes of expression in signaling pathways.

Results : Microarray analysis of the murine retina using the criteria of <-1.5 or >1.5 Fold change and ANOVA p-value <0.05 showed significant alteration in expression of 1114 transcript clusters at 1 week post- injection, including 98 coding and 386 non-coding RNAs (microRNAs, small nucleolar RNA, long-non-coding RNAs-lncRNA) and other novel transcripts. At 4 weeks post-injection, gene expression changes were observed in a total of 172 transcripts clusters. They included 19 coding and 20 non-coding genes. WikiPathways analysis identified expression changes in the Apoptosis pathway at both time points. Ingenuity Pathway Analysis (IPA) highlighted Phototransduction, Nervous System Development and Inherited Diseases affected at week 1, and Visual System Development &Function and Ophthalmic Diseases affected at week 4.

Conclusions : Microarray analysis of the degenerating retina shows alteration in expression of both coding and noncoding genes in response to intravitreal administration of human CD34+ cells. The non-coding RNAs, including miRNAs, known to have a key role in gene expression regulation at the post-transcriptional level appear to be the prevalent retinal transcripts at week 1. Gene pathways affected are very relevant to pathogenesis of hereditary retinal degeneration, and alterations in expression of these genes support a potential trophic regenerative effect of human CD34+ stem cells on the degenerating mouse retina.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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