Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 21, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/ijms21103541
Keywords
RPE; exosome; aging; microglia; inflammation
Funding
- NIH [EY 028773, EY 019706]
- NIGMS [P30 GM122744]
- BrightFocus Foundation
- International Retina Research Foundation
- Carl Marshall and Mildred Almen Reeves Foundation
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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.
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