# The role of limbal fibroblasts for the maintenance of limbal stem cells

> **NIH NIH R21** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2024 · $247,500

## Abstract

Project Summary / Abstract
Corneal epithelium is maintained by stem cells residing in the limbus, the area between the cornea and
conjunctiva. These stem cells are known as limbal stem cells (LSCs) and give rise to progenitor cells, which
migrate toward central and apical cornea to form the stratified corneal epithelial cell layers. Loss of LSCs result
in limbal stem cell deficiency (LSCD); the patients suffer from severe vision loss due to the ingrowth of cloudy
conjunctiva. While unilateral LSCD can be treated by transplantation of autologous limbal tissue, patients with
bilateral LSCD have to rely on allogeneic transplantation and the clinical outcome is relatively poor. In addition,
there are multiple post-operative complications reported including recurrent/persistent epithelial erosion,
intraocular pressure elevation, and rejection. Moreover, the shortage of corneal donors reduces the opportunity
for allogeneic transplantation. There is, therefore, a critical need to develop a less invasive therapy to treat
LSCD that also addresses the donor shortage. Besides the graft condition, it is important to control recipients’
limbal niche microenvironment for a successful transplantation, since there has been growing awareness of the
fact that limbal niche cells play a critical role for the maintenance of LSCs. Of the niche cells, limbal fibroblasts
are thought to contribute to the maintenance of corneal epithelial phenotype by secreting fibroblast growth
factor 7 (FGF7), whose secretion is promoted by platelet-derived growth factor (PDGF)-BB and interleukin 1
beta (IL1β). However, it remains largely unknown how limbal fibroblasts are affected in the LSCD and how the
recovery of limbal fibroblasts contributes to the success of the treatment of LSCD.
 Our long-term goal is to develop a novel treatment for LSCD by recovering the function of limbal niche.
Our overall objective in this proposal is to reveal the contribution of limbal fibroblasts in normal and LSCD
conditions, and to establish a limbal fibroblast injection as a novel LSCD therapy. Our central hypothesis is that
limbal fibroblasts secrete FGF7 in response to PDGF and IL1β secreted by limbal dendritic cells to maintain
the limbal stem/progenitor cells. Moreover, we hypothesize that limbal niche cells including limbal fibroblasts
are disrupted in LSCD and injection of limbal fibroblasts regenerate the corneal phenotype in LSCD. In
addition, we will utilize a novel technique of eye-like organoid formation from human induced pluripotent stem
cells (iPSCs) to create limbal fibroblasts as a cell source of injectable cells to resolve the corneal donor
shortage. Proposed study will reveal the characteristics of limbal fibroblasts and limbal dendritic cells (Aim 1),
evaluate the interaction of limbal niche cells and limbal epithelial cells (Aim 2), and establish limbal fibroblast
injection method for the treatment of mouse LSCD (Aim 3). Successful completion of this project will improve
our under...

## Key facts

- **NIH application ID:** 10986618
- **Project number:** 1R21EY035735-01A1
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Yuzuru Sasamoto
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $247,500
- **Award type:** 1
- **Project period:** 2024-08-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10986618

## Citation

> US National Institutes of Health, RePORTER application 10986618, The role of limbal fibroblasts for the maintenance of limbal stem cells (1R21EY035735-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10986618. Licensed CC0.

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