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 language | English |
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Article number | 2689 |
Journal | International Journal of Molecular Sciences |
Volume | 21 |
Issue number | 8 |
Early online date | 13 Apr 2020 |
DOIs | |
Publication status | Published - Apr 2020 |
Bibliographical note
Funding: This research was funded by the Deutsche Forschungsgemeinschaft (GR5065/1-1).Author Contributions: Conceptualization, F.G. and B.H.F.W.; Data curation, T.S.; Formal analysis, P.B., M.K., A.A., and T.S.; Funding acquisition, C.K. and F.G.; Investigation, M.K. and B.H.F.W.; Methodology, C.K. and A.A.;Project administration, B.H.F.W.; Resources, M.K., A.A., T.L., and F.G.; Software, C.K. and T.S.; Supervision, T.L., F.G., and B.H.F.W.; Validation, P.B.; Visualization, C.K.; Writing—original draft, C.K. and P.B.; Writing—review &
editing, B.H.F.W. All authors have read and agreed to the published version of the manuscript.
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
- Biomarker
- Laser-induced choroidal neovascularization
- CmiRNA regulation
- Age-related macular degeneration