TY - JOUR
T1 - A Circulating MicroRNA Profile in a Laser-Induced Mouse Model of Choroidal Neovascularization
AU - Kiel, Christina
AU - Berber, Patricia
AU - Karlstetter, Marcus
AU - Aslanidis, Alexander
AU - Strunz, Tobias
AU - Langmann, Thomas
AU - Grassmann, Felix
AU - Weber, Bernhard H F
N1 - 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.
PY - 2020/4
Y1 - 2020/4
N2 - 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.
AB - 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.
KW - cmiRNA regulations
KW - age-related macular degeneration
KW - laser-induced choroidal neovascularization
KW - biomarker
KW - CELLS
KW - ANGIOGENESIS
KW - POTENTIAL BIOMARKERS
KW - MACULAR DEGENERATION
KW - NATURAL-HISTORY
KW - IN-VITRO
KW - cmiRNA regulation
KW - GENETICS
KW - EXPRESSION
KW - ENDOTHELIAL GROWTH-FACTOR
KW - RETINAL-PIGMENT EPITHELIUM
KW - Biomarker
KW - Laser-induced choroidal neovascularization
KW - CmiRNA regulation
KW - Age-related macular degeneration
UR - http://www.scopus.com/inward/record.url?scp=85083479185&partnerID=8YFLogxK
U2 - 10.3390/ijms21082689
DO - 10.3390/ijms21082689
M3 - Article
C2 - 32294914
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1422-0067
IS - 8
M1 - 2689
ER -