# Extracellular microRNA-mediated intercellular communication between retinal microglia and RPE

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2024 · $436,544

## Abstract

The primary goals of this project are to investigate the transfer of extracellular microRNAs (miRNA) between
retinal pigment epithelium (RPE) and microglia as a means of intercellular communication and to evaluate the
use of engineered RPE-derived extracellular vesicles (EVs) as an interventional strategy to mitigate retinal
inflammation and injury. MicroRNAs are small RNA molecules that regulate gene expression by reducing the
stability of target messenger RNAs (mRNAs) and/or inhibiting mRNA translation into proteins. Cells release
miRNAs into EVs, including exosomes, which can be delivered to recipient cells to modify their functions. The
RPE and microglia are two important types of supporting cells in the neural retina that control the inflammation
and immune responses. In our published and preliminary studies, we found that retinal microglia can uptake
RPE-derived EVs; and their miRNA levels and signaling pathways can be influenced by these EVs and their
miRNA contents. The most abundant miRNA in RPE EVs is miR-204, which targets Tgfbr2 gene in microglia
and regulates lipid metabolism. RPE-derived EVs can improve microglial function in miR-204 knockout mice.
The current application aims to further investigate whether RPE EVs can rejuvenate the aging retinal microglia,
and to use computational modeling to define a dynamic and condition-specific regulatory relationships between
miRNAs and mRNAs in microglia. Additionally, experiments will be performed to examine whether EVs
produced by human iPSC-RPE cells can be engineered for enhanced protective functions. The results of these
studies will provide insights into how EVs and their associated miRNAs mediate signal transduction between
two distinct cell types in the outer retina. The findings could also guide future applications of EV-based delivery
of miRNA mimics or related compounds to modulate microglia function and alleviate the progression of age-
related retinal diseases.

## Key facts

- **NIH application ID:** 10978578
- **Project number:** 1R01EY035855-01A1
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** JIYANG CAI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $436,544
- **Award type:** 1
- **Project period:** 2024-09-30 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10978578

## Citation

> US National Institutes of Health, RePORTER application 10978578, Extracellular microRNA-mediated intercellular communication between retinal microglia and RPE (1R01EY035855-01A1). Retrieved via MORVS 2026-10-27 from https://api.morvs.ai/grant/nih/10978578. Licensed CC0.

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