A Circulating MicroRNA Profile in a Laser-Induced Mouse Model of Choroidal Neovascularization

Christina Kiel, Patricia Berber, Marcus Karlstetter, Alexander Aslanidis, Tobias Strunz, Thomas Langmann, Felix Grassmann, Bernhard H F Weber* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Choroidal neovascularization (CNV) is a pathological process in which aberrant blood vessels invade the subretinal space of the mammalian eye. It is a characteristic feature of the prevalent neovascular age-related macular degeneration (nAMD). Circulating microRNAs (cmiRNAs) are regarded as potentially valuable biomarkers for various age-related diseases, including nAMD. Here, we investigated cmiRNA expression in an established laser-induced CNV mouse model. Upon CNV induction in C57Bl/6 mice, blood-derived cmiRNAs were initially determined globally by RNA next generation sequencing, and the most strongly dysregulated cmiRNAs were independently replicated by quantitative reverse transcription PCR (RT-qPCR) in blood, retinal, and retinal pigment epithelium (RPE)/choroidal tissue. Our findings suggest that two miRNAs, mmu-mir-486a-5p and mmur-mir-92a-3p, are consistently dysregulated during CNV formation. Furthermore, in functional in vitro assays, a significant impact of mmu-mir-486a-5p and mmu-mir-92a-3p on murine microglial cell viability was observed, while mmu-mir-92a-3p also showed an impact on microglial mobility. Taken together, we report a robust dysregulation of two miRNAs in blood and RPE/choroid after laser-induced initiation of CNV lesions in mice, highlighting their potential role in pathology and eventual therapy of CNV-associated complications.

Original languageEnglish
Article number2689
Journal International Journal of Molecular Sciences
Volume21
Issue number8
Early online date13 Apr 2020
DOIs
Publication statusPublished - Apr 2020

Keywords

  • cmiRNA regulations
  • age-related macular degeneration
  • laser-induced choroidal neovascularization
  • biomarker
  • CELLS
  • ANGIOGENESIS
  • POTENTIAL BIOMARKERS
  • MACULAR DEGENERATION
  • NATURAL-HISTORY
  • IN-VITRO
  • cmiRNA regulation
  • GENETICS
  • EXPRESSION
  • ENDOTHELIAL GROWTH-FACTOR
  • RETINAL-PIGMENT EPITHELIUM

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