# Mechanisms of Neuroregulation of Corneal Angiogenesis

> **NIH NIH K08** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2022 · $54,000

## Abstract

ABSTRACT (From Original Application)
This proposal describes a 3-year training program for the development of an academic career focused on
understanding the mechanisms of neuroregulation of corneal angiogenesis. The candidate Jia Yin, M.D.,
Ph.D. is an Assistant Professor of Ophthalmology at Massachusetts Eye and Ear Infirmary, Harvard Medical
School. She has scientific training in the field of corneal wound healing, angiogenesis, and immunology, and
clinical training in corneal diseases. Dr. Yin’s long-term goal is to advance the scientific understanding and
clinical treatment of blinding corneal diseases. In this 3-year career development plan, she proposes to1)
enhance scientific knowledge and techniques in neuroscience, angiogenesis and immunology, 2) hone
grantsmanship, and 3) develop leadership and managerial skills, through coursework, seminars, and meetings
with clearly defined milestones. The advisory committee includes mentor Dr. Reza Dana, renowned clinician
scientist in corneal diseases and ocular immunology, and co-mentor Dr. Patricia D'Amore, scientific leader in
the field of angiogenesis and retinal vascular diseases. The proposed research and career development plans
will take place in the rich environments of Massa Eye and Ear and Harvard Medical School. The proposed
research plan examines the direct relationship between blood vessels and nerves in the cornea. We have
found that neurons isolated from the trigeminal ganglion, from which corneal nerves originate, directly inhibit
vascular endothelial cell activities. In addition, neurons isolated from mice with ocular surface inflammation
lose their anti-angiogenic function. Based on these data, we hypothesize that under normal conditions corneal
nerves directly modulate angiogenesis via secreted neuropeptides, and that dysregulation of these
neuropeptides after ocular surface inflammation promotes corneal neovascularization. Specifically, we propose
that alpha-melanocyte-stimulating hormone, an immune-modulatory neuropeptide secreted by corneal nerves,
contributes to the inhibition of angiogenesis under normal conditions (Aim 1). In addition, we propose that
secretion of substance P, a key mediator of neurogenic inflammation, by corneal nerves is increased after
acute ocular surface inflammation and this increase directly promotes corneal neovascularization (Aim 2). A
unique and innovative in vitro co-culture system of trigeminal neurons and vascular endothelial cells will be
used to examine these hypotheses in Aims 1 and 2. In Aim 3, we will use a suture-induced corneal
neovascularization mouse model to determine the roles of these neuropeptides in vivo. The proposed research
is of high relevance in ocular tissues and non-ocular settings characterized by peripheral nerve inflammation
and degeneration. Successful completion of the proposal can lead to the development of therapeutics for
corneal neovascularization and neuro-inflammation.

## Key facts

- **NIH application ID:** 10649841
- **Project number:** 3K08EY031340-03S1
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Jia Yin
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $54,000
- **Award type:** 3
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10649841

## Citation

> US National Institutes of Health, RePORTER application 10649841, Mechanisms of Neuroregulation of Corneal Angiogenesis (3K08EY031340-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10649841. Licensed CC0.

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