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A Mouse Model for Laser-induced Choroidal Neovascularization
Published on: December 27, 2015
A Circulating MicroRNA Profile in a Laser-Induced Mouse Model of Choroidal Neovascularization
Christina Kiel1, Patricia Berber1, Marcus Karlstetter2
1Institute of Human Genetics, University of Regensburg, 93053 Regensburg, Germany.
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.
Insights
Two specific microRNAs (mmu-mir-486a-5p and mmu-mir-92a-3p) were found to be dysregulated in circulating and ocular tissues during choroidal neovascularization (CNV) development in a mouse model. These microRNAs impact microglial cell function, suggesting a role in CNV pathology.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Choroidal neovascularization (CNV) is a key pathological process in neovascular age-related macular degeneration (nAMD).
- Circulating microRNAs (cmiRNAs) show promise as biomarkers for age-related diseases like nAMD.
Purpose of the Study:
- To investigate cmiRNA expression changes in a laser-induced CNV mouse model.
- To identify specific cmiRNAs involved in CNV pathogenesis and their functional impact.
Main Methods:
- Laser-induced CNV model in C57Bl/6 mice.
- Global cmiRNA profiling using RNA next-generation sequencing.
- Quantitative reverse transcription PCR (RT-qPCR) for validation in blood and ocular tissues (retina, RPE/choroid).
- In vitro functional assays on murine microglial cells.
Main Results:
- Two miRNAs, mmu-mir-486a-5p and mmu-mir-92a-3p, were consistently dysregulated during CNV formation.
- These miRNAs were detected in circulating blood and ocular tissues (RPE/choroid).
- Both miRNAs affected murine microglial cell viability; mmu-mir-92a-3p also impacted microglial mobility.
Conclusions:
- Robust dysregulation of mmu-mir-486a-5p and mmu-mir-92a-3p occurs post-CNV induction in mice.
- These miRNAs may play a role in the pathology of CNV and associated complications.
- Dysregulated miRNAs present potential therapeutic targets for CNV-associated diseases.
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