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A Protocol to Evaluate and Quantify Retinal Pigmented Epithelium Pathologies in Mouse Models of Age-Related Macular Degeneration
Published on: March 10, 2023
Construction of a ferroptosis-associated circRNA-miRNA-mRNA network in age-related macular degeneration
1Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China; National Clinical Research Center for Ophthalmic Diseases, Shanghai, China.
Abstract:
Age-related macular degeneration (AMD) is a leading cause of severe vision impairment in the aging population. However, the underlying molecular mechanism remains unclear. Ferroptosis is a novel non-apoptotic programmed cell death pathway, that contributes to AMD. In addition, non-coding RNA-led epigenetic profile was identified in the regulation of AMD progression. Considering that non-coding RNAs are vital regulators of ferroptosis-related genes in various pathological events, we explored and constructed a ferroptosis-associated circRNA-miRNA-mRNA network in AMD. Differential expression of fourteen ferroptosis-associated genes were identified based on our microarray analysis and the FerrDb tool at the threshold of P < 0.05 and log2|fold change| ≥ 1, which were subsequently validated by the public datasets. We further screened eight miRNAs via public datasets and the miRNet database. Based on these eight miRNAs, 23 circRNAs were mined using the Starbase tool. Taking all these together, we obtained a ferroptosis-related network with 414 pairs of circRNA-miRNA-mRNA, which are potential targets in future AMD treatments.
Insights
Age-related macular degeneration (AMD) involves ferroptosis, a cell death pathway. Researchers constructed a ferroptosis-associated circRNA-miRNA-mRNA network, identifying potential therapeutic targets for AMD.
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Age-related macular degeneration (AMD) is a primary cause of vision loss in older adults.
- The molecular mechanisms driving AMD progression are not fully understood.
- Ferroptosis, a programmed cell death pathway, and non-coding RNAs are implicated in AMD pathogenesis.
Purpose of the Study:
- To explore and construct a ferroptosis-associated circRNA-miRNA-mRNA regulatory network in AMD.
- To identify novel molecular targets for AMD treatment.
Main Methods:
- Differential expression analysis of ferroptosis-related genes using microarray data and FerrDb.
- Validation of gene expression using public datasets.
- Screening of miRNAs and circRNAs using public databases (miRNet, Starbase).
Main Results:
- Identified 14 differentially expressed ferroptosis-associated genes.
- Screened 8 miRNAs and 23 circRNAs.
- Constructed a comprehensive ferroptosis-related network comprising 414 circRNA-miRNA-mRNA interactions.
Conclusions:
- The constructed network provides insights into the molecular mechanisms of AMD.
- The identified circRNA-miRNA-mRNA interactions represent potential therapeutic targets for AMD.
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