# Mechanisms of Neuroregulation of Corneal Angiogenesis

> **NIH NIH K08** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2020 · $238,682

## Abstract

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, co-mentor Dr. Patricia D'Amore, scientific leader in the
field of angiogenesis and retinal vascular diseases, and collaborator Dr. Gabriel Corfas, an expert in
neuroscience and peripheral nerve degeneration. The proposed research and career development plans will
take place in the rich environments of Schepens Eye Research Institute, Massachusetts Eye and Ear
Infirmary, Harvard Medical School, and Harvard School of Public Health.
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 ...

## Key facts

- **NIH application ID:** 9948355
- **Project number:** 1K08EY031340-01
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** Jia Yin
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $238,682
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948355

## Citation

> US National Institutes of Health, RePORTER application 9948355, Mechanisms of Neuroregulation of Corneal Angiogenesis (1K08EY031340-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9948355. Licensed CC0.

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