# Hyaluronan in the cornea: Regulation of limbal stem cell fate and lymphangiogenesis

> **NIH NIH R01** · UNIVERSITY OF HOUSTON · 2020 · $382,500

## Abstract

Project summary
Limbal stem cells (LSCs) are required for reconstituting the corneal epithelium after injury. Injury to the
cornea leading to substantial damage of LSCs or the LSC niche (LSCN) may lead to LSC deficiency
(LSCD), a serious medical condition that causes corneal opacification, inflammation, vascularization, severe
pain and conjunctivalization, and which can ultimately lead to complete loss of vision. The transplantation of
LSCs expanded ex vivo onto the damaged cornea is a common surgical procedure that is carried out all
around the world with an overall success rate of 60%- 70%. A major hurdle in culturing LSCs ex vivo is that
they readily differentiate into central corneal epithelial cells, hampering their use for therapeutic applications
and underscoring the need to regenerate the LSCN microenvironment in vitro for LSC expansion.
Interestingly, our recently published work demonstrates that the LSCN is composed of an hyaluronan (HA)
rich matrix which is required to support the stem cell phenotype. Aim 1 of this proposal will characterize the
precise composition of the complex HA matrix present in the LSCN. Aim 2 will work towards reproducing
the matrix present in the LSCN in culture conditions for ex vivo expansion of LSCs and also establishing
how the HA matrix present in the LSCN regulates the LSC phenotype in vivo. Lymphatic vessels are
present solely in the limbus (the HA rich region of the cornea) and the cornea is therefore avascular. Ocular
injuries and inflammation, such as LSCD, often lead to irreversible corneal angiogenesis and
lymphangiogenesis, which reduce corneal transparency, leading to vision loss and limiting the success of
LSC transplantation. The lymphatic vessel marker Lyve-1 (LYmphatic Vessel Endothelial receptor 1) is a
hyaladherin (a protein that specifically binds HA) and is expressed throughout the lymphatic system. Lyve-1
is capable of binding both soluble and immobilized HA; however, whether the HA/Lyve-1 interaction plays a
role in lymphangiogenesis remains elusive. Interestingly, our preliminary data reveal that corneas of HA
knock-out mice show only vestigial lymphatic vessels in the limbus, suggesting that an HA scaffold may be
necessary for corneal lymphangiogenesis. HA up-regulation throughout the cornea precedes exacerbated
extension of lymphatic vessels, and injecting HA into the corneal stroma leads to the extension of lymphatic
vessels. Therefore, we postulate that HA plays an important role in regulating corneal lymphangiogenesis.
Aim 3 proposes to identify the mechanism by which HA within the corneal limbus regulates the
development of lymphatic vessels.

## Key facts

- **NIH application ID:** 9967005
- **Project number:** 5R01EY029289-03
- **Recipient organization:** UNIVERSITY OF HOUSTON
- **Principal Investigator:** Vivien Jane Coulson-Thomas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $382,500
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9967005

## Citation

> US National Institutes of Health, RePORTER application 9967005, Hyaluronan in the cornea: Regulation of limbal stem cell fate and lymphangiogenesis (5R01EY029289-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9967005. Licensed CC0.

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