# Modulation of VEGF receptors to prevent limbal stem cell transplant rejection

> **NIH VA I01** · JESSE BROWN VA MEDICAL CENTER · 2021 · —

## Abstract

Modulation of VEGF receptors to prevent Limbal Stem Cell Transplant rejection
Abstract:
The ranking of ocular trauma as the fourth most common injury among combat personnel
indicates the vital importance of evaluating and promoting ocular health among veterans.
Corneal neovascularization, or the growth of new blood vessels (angiogenesis) and new
lymphatic vessels (lymphangiogenesis) in the cornea, often results from infection or severe
corneal injury caused by explosion pressure, penetration by debris, or long-term exposure to dry
environments. Almost eight million people worldwide are afflicted with blindness secondary to
such corneal disease. Even larger numbers of people are suffering from ocular discomfort
caused by ocular surface disease from mechanical, chemical, immune or thermal trauma.
Military persons are at high risk since they are exposed to such environment frequently. And
also insufficiency of adequate and timely treatment is major problem on the field which is the
main cause for condition getting worse. Trauma to the ocular surface, damage to the limbal area
results in the loss of Limbal stem cells, and cause Limbal Stem Cell Deficiency (LSCD). At
present Limbal Stem Cell Transplantation (LSCT) is prominent way to treat LSCD. Although,
LSCT induces faster epithelialization, without the use of systemic immunosuppression, the
rejection rate of LSC transplants is as high as 70%.
Vascular endothelial growth factors (VEGFs) and membrane-bound (mb) VEGF receptors
(mbVEGFR1, R2, and R3) have been identified as modulators of corneal angiogenesis and
lymphangiogenesis and therefore regulates Limbal Stem Cell Transplantation rejection.
VEGFR1, R2 and R3 specifically are the primary mediators of angiogenesis and
lymphangiogenesis in the corneal stroma and epithelium. Here we propose to use high-risk
mouse Limbal Stem Cell Transplantation models with conditional (CDh5-CreERT2 and Prox1-
CreERT2) knockout of mbVEGFR1, 2, or 3 in vascular and lymphatic endothelial cells to
determine the most effective strategies for inhibiting corneal blood and lymphatic vessel growth.
In doing so, we hope to identify components that effectively modulate corneal
neovascularization in order to facilitate the future development of drugs that will block injury
induced corneal angiogenesis and lymphangiogenesis and further improve Limbal Stem Cell
Transplantation success rates. Our research will bear implications not only pertinent to the
Veteran Affairs healthcare mission by promoting ocular health and preventing blindness among
veterans, but also indicate methods for successful transplantation of other tissues in addition to
the Limbal Stem Cell.

## Key facts

- **NIH application ID:** 10155431
- **Project number:** 5I01BX004234-03
- **Recipient organization:** JESSE BROWN VA MEDICAL CENTER
- **Principal Investigator:** JIN-HONG CHANG
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155431

## Citation

> US National Institutes of Health, RePORTER application 10155431, Modulation of VEGF receptors to prevent limbal stem cell transplant rejection (5I01BX004234-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10155431. Licensed CC0.

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