A Circulating MicroRNA Profile in a Laser-Induced Mouse Model of Choroidal Neovascularization.
Christina KielPatricia BerberMarcus KarlstetterAlexander AslanidisTobias StrunzThomas LangmannFelix GrassmannBernhard Heinrich Friedrich WeberPublished in: International journal of molecular sciences (2020)
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.
Keyphrases
- age related macular degeneration
- mouse model
- optical coherence tomography
- diabetic retinopathy
- inflammatory response
- vascular endothelial growth factor
- high fat diet induced
- lipopolysaccharide induced
- poor prognosis
- high resolution
- lps induced
- transcription factor
- high throughput
- optic nerve
- type diabetes
- bone marrow
- mass spectrometry
- metabolic syndrome
- cell therapy
- deep learning
- skeletal muscle
- atomic force microscopy