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

• Published in: International journal of molecular sciences 2020-04, Vol.21 (8), p.2689
• Main Authors: Kiel, Christina, Berber, Patricia, Karlstetter, Marcus, Aslanidis, Alexander, Strunz, Tobias, Langmann, Thomas, Grassmann, Felix, Weber, Bernhard H F
• Format: Article
• Language: English
• Subjects: age-related macular degeneration; Animals; biomarker; Blood vessels; Cell viability; Cells, Cultured; Choroidal Neovascularization - blood; Choroidal Neovascularization - etiology; Choroidal Neovascularization - metabolism; Choroidal Neovascularization - pathology; Circulating MicroRNA - genetics; cmiRNA regulation; Disease Models, Animal; Disease Susceptibility; Endothelial Cells - metabolism; Epithelium; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation; High-Throughput Nucleotide Sequencing; Independent study; laser-induced choroidal neovascularization; Lasers; Lasers - adverse effects; Macular degeneration; Medicin och hälsovetenskap; Mice; Microglia - metabolism; MicroRNAs; MicroRNAs - genetics; miRNA; Next-generation sequencing; Patients; Retina; Retina - metabolism; Retinal pigment epithelium; Retinal Pigment Epithelium - metabolism; Reverse transcription; Studies; Transcriptome; Vascularization
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21082689

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.