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MicroRNA Expression Profiles of Human iPS Cells, Retinal Pigment Epithelium Derived From iPS, and Fetal Retinal Pigment Epithelium
Published on: June 24, 2014
Exosomal MiRNA Transfer between Retinal Microglia and RPE
Dorothea R Morris1, Sarah E Bounds2, Huanhuan Liu2
1Department of Ophthalmology & Visual Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Abstract:
The retinal pigment epithelium (RPE), the outermost layer of the retina, provides essential support to both the neural retina and choroid. Additionally, the RPE is highly active in modulating functions of immune cells such as microglia, which migrate to the subretinal compartment during aging and age-related degeneration. Recently, studies have highlighted the important roles of microRNA (miRNA) in the coordination of general tissue maintenance as well as in chronic inflammatory conditions. In this study, we analyzed the miRNA profiles in extracellular vesicles (EVs) released by the RPE, and identified and validated miRNA species whose expression levels showed age-dependent changes in the EVs. Using co-culture of RPE and retinal microglia, we further demonstrated that miR-21 was transferred between the two types of cells, and the increased miR-21 in microglia influenced the expression of genes downstream of the p53 pathway. These findings suggest that exosome-mediated miRNA transfer is a signaling mechanism that contributes to the regulation of microglia function in the aging retina.
Insights
Retinal pigment epithelium (RPE) releases extracellular vesicles (EVs) containing age-dependent microRNAs (miRNAs). This transfer to microglia influences aging retina gene expression, suggesting a novel signaling pathway.
Area of Science:
- Ophthalmology
- Molecular Biology
- Cell Biology
Background:
- The retinal pigment epithelium (RPE) supports retinal health and modulates immune cells like microglia.
- Microglia migrate to the subretinal space during aging and degeneration.
- MicroRNAs (miRNAs) are crucial in tissue maintenance and inflammation.
Purpose of the Study:
- To analyze miRNA profiles in RPE-derived extracellular vesicles (EVs).
- To identify age-dependent miRNA changes in RPE EVs.
- To investigate the role of miRNA transfer in RPE-microglia communication during aging.
Main Methods:
- Analysis of miRNA profiles in extracellular vesicles (EVs) from RPE.
- Identification and validation of age-dependent miRNAs in EVs.
- Co-culture experiments with RPE and retinal microglia to study miRNA transfer.
- Assessment of miR-21 transfer and its downstream effects on the p53 pathway in microglia.
Main Results:
- Age-dependent changes in miRNA expression were identified in RPE-derived EVs.
- miR-21 was found to be transferred from RPE to microglia.
- Increased miR-21 in microglia affected the expression of p53 pathway target genes.
Conclusions:
- Exosome-mediated miRNA transfer is a key mechanism for RPE-microglia communication.
- This signaling pathway regulates microglia function in the aging retina.
- Findings provide insights into age-related retinal degeneration and potential therapeutic targets.

