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Publication
Visualizing HIF-1a mRNA in a Subpopulation of Bone Marrow-Derived Cells to
Predict Retinal Neovascularization.
Authors Uddin MI, Kilburn TC, Duvall CL, Penn JS
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal ACS chemical biology
Year 2020
Date Published 11/1/2020
Volume : Pages 15 : 3004 - 3012
PubMed Reference 33080135
Abstract Bone marrow-derived progenitor cells and macrophages are known to migrate into
the retina in response to inflammation and neovascularization. These migratory
cells might play important regulatory roles in the pathogenesis of
neovascularization, a common complication observed in diabetic retinopathy,
retinopathy of prematurity, and retinal vein occlusion. Hypoxia-inducible factor
1a (HIF-1a) has been shown to contribute to the pathogenesis of retinal
inflammation and neovascularization. However, contributions of monocyte-derived
macrophages to neovascularization are largely unknown. We hypothesized that
selective visualization of these microglia/macrophages could be a powerful
method for predicting the onset of neovascularization and its progression at the
molecular level. In this report, we describe the synthesis of a new hybrid
nanoparticle to visualize HIF-1a mRNA selectively in microglia/macrophages in a
mouse model of neovascularization. HIF-1a expression was confirmed in MRC-1
positive monocytes/macrophages as well as in CD4 positive T-cells and CD19
positive B-cells using single-cell RNA sequencing data analysis. The imaging
probes (AS- or NS-shRNA-lipid) were synthesized by conjugating diacyl-lipids to
short hairpin RNA with an antisense sequence complementary to HIF-1a mRNA and a
fluorophore that is quenched by a black hole quencher. We believe that imaging
mRNA selectively in tissue specific microglia/macrophages could be a powerful
method for predicting the onset of neovascularization, its progression, and its
response to therapy.




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