# Molecular Regulation of Lymphangiogenesis in Corneal Alloimmunity

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA BERKELEY · 2020 · $392,500

## Abstract

Project Summary
Lymphatic research denotes an explosive field of new discovery and lymphatic dysfunction has been found in
myriad of diseases. To date, there is still a significant lack of effective treatments for lymphatic diseases in
general. The cornea offers an ideal site for lymphatic research due to its accessible location, transparent
nature, and lymphatic-free and -inducible features. It is also found that corneal lymphatic vessels develop
luminal valves as lymphangiogenesis (LG) proceeds. Studies on corneal LG bears direct implications to
transplant rejection in both lamellar and penetrating transplantation settings. The rejection rate of high-risk
transplants can be as high as 90%, irrespective of current treatment modalities. However, many patients who
are blind from corneal diseases fall into this category after an inflammatory, infectious, traumatic or chemical
insult. Our long-term goal is to elucidate the underlying mechanisms of LG using various in vivo corneal
models and in vitro cell culture systems, a necessary prerequisite to the development of new therapeutic
protocols. Our main hypothesis is that corneal LG is mediated by specific lymphatic factors and the
interactions between lymphatic endothelial cells (LECs) and extracellular matrix (ECM), which can be
modulated to interfere with LG and graft rejection. This proposal is based on the most recent advances in
technology and lymphatic research, and a large amount of preliminary data we have generated during the past
few years. Our specific aims are: 1) investigate LG and valve formation in lamellar corneal transplantation
using lymphatic fluorescent transgenic mice, live imaging technology, and neutralizing antibodies; 2) define the
interaction between LECs and ECM using LEC culture system and mutant mice; and 3) assess the role of
Wnt5a in high-risk corneal transplantation using conditional knockout mice and siRNAs. Research on corneal
LG has broader clinical implications beyond the treatment of ocular diseases alone since lymphatic
dysfunction is associated with a wide array of disorders, which include but are not limited to cancer metastasis,
diabetes, inflammation, infection, obesity, hypertension and lymphedema.

## Key facts

- **NIH application ID:** 9942406
- **Project number:** 5R01EY017392-13
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** LU CHEN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $392,500
- **Award type:** 5
- **Project period:** 2007-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9942406

## Citation

> US National Institutes of Health, RePORTER application 9942406, Molecular Regulation of Lymphangiogenesis in Corneal Alloimmunity (5R01EY017392-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9942406. Licensed CC0.

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