# Corneal Epithelial-Stromal Interactions During Regeneration and Fibrosis

> **NIH NIH R01** · SCHEPENS EYE RESEARCH INSTITUTE · 2020 · $492,500

## Abstract

PROJECT SUMMARY
Cell-cell communication is an important component of most functions of the cornea, including fibrosis,
regeneration, and homeostasis. To a great extent, cell-cell communication has been thought to consist of the
release of numerous soluble growth factors and cytokines to direct corneal wound repair; however an
underlying question remains as to how these factors perfuse with any specificity from one cell to an adjacent
cell. Recently, interest in another method of cell-communication has boomed. This method involves the
secretion and uptake of small vesicles, termed Extracellular Vesicles (EVs). EVs can migrate long and short
distances to be taken up by other cells. This crosstalk between cells is notable in that EVs carry “cargo”
consisting of proteins, mRNA, miRNA, and DNA that can influence many of the functions in the recipient cell.
Indeed, recent findings indicate that development of cancer involves crosstalk with EVs, where cancer cells
produce EVs that act on the host's cells to produce a microenvironment that promotes growth of cancer cells.
We propose to examine if corneal wound healing involves a similar mechanism, where epithelial cells release
EVs that alter the properties of keratocytes. We have found that epithelial EVs can stimulate keratocytes to
become myofibroblasts and that epithelial EVs from wounded cells have an even greater effect. This has lead
us to the hypothesis that the epithelial EV cargo is altered as cells become migratory to heal a wound,
subsequently causing the keratocyte to become myofibroblasts, which produce a microenvironment that
promotes their persistence. Because of its clarity and accessibility, the cornea provides an outstanding model
to examine movement of EVs through matrix in in vivo or ex vivo models. Techniques to be used include EV
isolation, proteomics. miRNA isolation and characterization, transmission electron microscopy, confocal
microscopy, and 3D cultures. Relevance to Public Health—EVs are involved in cell-cell communication in
virtually all physiological and pathological processes. Because of their ability to travel long distances and
interact with specific cells, EVs are widely being examined for usefulness to deliver therapeutics. We will
determine if topical application of EVs to the cornea is useful as a therapeutic approach. Potentially, any
corneal injury or disease could be treated with EVs.

## Key facts

- **NIH application ID:** 9893920
- **Project number:** 5R01EY005665-35
- **Recipient organization:** SCHEPENS EYE RESEARCH INSTITUTE
- **Principal Investigator:** Joseph B. Ciolino
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $492,500
- **Award type:** 5
- **Project period:** 1984-12-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893920

## Citation

> US National Institutes of Health, RePORTER application 9893920, Corneal Epithelial-Stromal Interactions During Regeneration and Fibrosis (5R01EY005665-35). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9893920. Licensed CC0.

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