June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Varied gene expression in murine retina after intravitreal injection of human CD34+ stem cells in eyes with retinal degeneration or diabetic retinopathy.
Author Affiliations & Notes
  • Jason Chow
    Ophthalmology & Vision Science, University of California Davis Health System, Sacramento, California, United States
  • Zeljka Smit-McBride
    Ophthalmology & Vision Science, University of California Davis Health System, Sacramento, California, United States
  • Elad Moisseiev
    Ophthalmology & Vision Science, University of California Davis Health System, Sacramento, California, United States
    Ophthalmology, Meir Medical Center, Tel Aviv, Israel
  • Amirfarbod Yazdanyar
    Ophthalmology & Vision Science, University of California Davis Health System, Sacramento, California, United States
    Ophthalmology, State University of New York Upstate Medical University, Syracuse, New York, United States
  • Whitney Cary
    Stell Cell Program, Institute for Regenerative Cures, University of California Davis, Sacramento, California, United States
  • Jan Nolta
    Stell Cell Program, Institute for Regenerative Cures, University of California Davis, Sacramento, California, United States
  • Susanna S Park
    Ophthalmology & Vision Science, University of California Davis Health System, Sacramento, California, United States
  • Footnotes
    Commercial Relationships   Jason Chow, None; Zeljka Smit-McBride, None; Elad Moisseiev, None; Amirfarbod Yazdanyar, None; Whitney Cary, None; Jan Nolta, None; Susanna Park, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 3319. doi:
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      Jason Chow, Zeljka Smit-McBride, Elad Moisseiev, Amirfarbod Yazdanyar, Whitney Cary, Jan Nolta, Susanna S Park; Varied gene expression in murine retina after intravitreal injection of human CD34+ stem cells in eyes with retinal degeneration or diabetic retinopathy.. Invest. Ophthalmol. Vis. Sci. 2021;62(8):3319.

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

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Abstract

Purpose : Previous studies have shown that intravitreal injection of healthy human CD34+ bone marrow stem cells (BMSCs) can result in regenerative or protective effects on the retina in eyes with retinal degeneration or diabetic retinopathy (DR). This study compared the gene expression changes in the retina resulting from intravitreal injection of human CD 34+ BMSCs in eyes with retinal degeneration versus DR to test the hypothesis that CD34+ BMSCs can have regenerative or protective effects on the retina via differing molecular mechanisms depending on retinal pathology.

Methods : Mice with retinal degeneration (rd1 mice) or diabetic retinopathy (streptozotocin-induced diabetic mice) had chronic systemic immunosuppression maintained to avoid rejection of human cells via placement of an Alzet subcutaneous pump to deliver tacrolimus and rapamycin. The right eye received intravitreal injection PBS (control) or healthy human CD34+ BMSC (50k cells) harvested via magnetic beads from bone marrow. These animals were euthanized at week 1, retinas were harvested, total RNA isolated and microarray analysis was performed on RNA samples. Gene expression changes (Fold Change <-1.5 or >+1.5, ANOVA P <0.05) between CD34+ BMSC injected and PBS injected control eyes were identified and compared between the two different murine models. Ingenuity pathway analysis was then performed on these overlaying genes to identify the pathways involved.

Results : Microarray analysis of the murine retina revealed changes in gene expression of 5275 and 331 genes in eyes with retinal degenerative and DR, respectively, compared to control eyes. Only 38 of these genes were altered in both rd1 and DR murine retina. These common genes include genes involved in pathways regulating photo-transduction, ocular angiogenesis, vascular endothelial growth factor signaling and inflammatory response. The genes uniquely altered in rd1 murine retina included those regulating cell cycle and growth, gene expression and repair, and immune response. The genes uniquely altered in DR murine retina included genes regulating ocular angiogenesis and cell cycle.

Conclusions : The protective effects of human CD34+ BMSCs following intravitreal injection appear to be via multiple molecular pathways that may be common and unique depending on the retinal pathology.

This is a 2021 ARVO Annual Meeting abstract.

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