# The Role of MicroRNAs in Corneal Epithelial Homeostasis

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $397,703

## Abstract

PROJECT SUMMARY/ABSTRACT
The anterior surface of the eye functions as a barrier to the external environment and protects the delicate
underlying structures from injury, in part, through the elaboration of the limbal and corneal epithelia. It is well-
accepted that the limbal epithelium is the site of the corneal epithelial stem cells, which are crucial for
maintaining the corneal epithelium; however, major questions remain unresolved concerning how the limbal
epithelium is regulated. microRNAs (miRNAs) are a major class of regulatory molecules that are part of the
RNAi silencing machinery. We demonstrated that miR-184 was the most abundant corneal epithelial miRNA,
and that miR-184 had marked angiostatic properties, which makes excellent biological sense as it is vital that
the cornea maintains avascularity. Surprisingly, given the prominence of miR-184 in limbal/corneal epithelial
biology, little is known about its regulation. Our recent evidence suggests that miR-184 is negatively regulated
by Ephrin-A3 (EFNA3), a member of the Eph/ephrin receptor tyrosine kinase family. EFNA3, is primarily
restricted to limbal epithelial basal cells. Interestingly, overexpression of EFNA3 significantly reduced miR-184
levels. Furthermore, another corneal-preferred miRNA, miR-210, targets EFNA3, which could indirectly
maintain miR-184 levels in the corneal epithelium. The lack of miR-210 in the limbal epithelium likely accounts
for limbal epithelial EFNA3 expression. Our hypothesis is that a EFNA3/miR-210 axis negatively regulates
miR-184, which enables proper limbal vascularity, an essential component of the stem cell niche; a relatively
understudied area. To test this hypothesis, we will modulate miRNA and target protein levels in submerged
cultures of human limbal and corneal epithelial cells and human microvascular endothelial cells. We will assess
the functional consequences of such miRNA and protein modulations with a combination of biochemical,
molecular biological, cell biological and physiological approaches. Another goal of this proposal is to realize the
unlimited potential of miRNAs as therapeutic interventions to affect diseased tissues. Preliminary data
indicates that a novel high density lipoprotein (HDL)-nanoparticle (NP) can deliver functional miRNAs into
human corneal epithelial cells. Excitingly, when a Cy-3-taged HDL-NP solution was applied topically to resting
mouse corneas, the Cy-3-tagged HDL-NPs were detected in the cytoplasm of corneal epithelial basal and wing
cells. We propose to focus on how miR-HDL-NPs affect the biology of limbal/corneal epithelia in vivo. To
accomplish this, we will use diabetic mice as a model of compromised corneal epithelial wound healing and
topically treat with a HDL-NP conjugated miR-205, a pro-migration miRNA. We will also use mice lacking
angiotensin converting enzyme 2 (ACE2) as a model of chronic corneal inflammation (e.g., bacterial keratitis or
dry eye) and topically treat with a HDL-NP conjugated miR-...

## Key facts

- **NIH application ID:** 10242730
- **Project number:** 5R01EY019463-12
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** ROBERT M LAVKER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $397,703
- **Award type:** 5
- **Project period:** 2010-06-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242730

## Citation

> US National Institutes of Health, RePORTER application 10242730, The Role of MicroRNAs in Corneal Epithelial Homeostasis (5R01EY019463-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10242730. Licensed CC0.

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