# Lipid Mediators in Corneal Nerve Regeneration

> **NIH NIH R01** · LSU HEALTH SCIENCES CENTER · 2020 · $365,000

## Abstract

Abstract
Alterations in corneal innervation result in impaired corneal sensation, severe dry eye and damage to the
epithelium that may in turn lead to corneal ulcers, melting and perforation. These alterations frequently occur
after refractive surgery, cornea transplant, herpetic infection, chemical burns, keratoconus, multiple sclerosis,
Sjogren’s syndrome, aging and diabetes mellitus. Although there are treatments to alleviate severe dry eye,
there are no therapies to compensate for the loss of innervation. This research project builds upon our finding
that pigment epithelium-derived factor (PEDF) plus the w-3 fatty acid docosahexaenoic acid (DHA) or the
docosanoid derivative neuroprotectin D1 (NPD1) stimulate nerve regeneration after corneal surgery that
damages the stromal nerves. We have recently found that: 1) corneas stimulated with PEDF+DHA also
synthesize other docosanoids, one of them identified as resolvin D6 (RvD6); 2) treatment with PEDF results in
activation of a calcium independent phospholipase A2ζ (iPLA2ζ); and 3) treatment also stimulates the gene
expression in the cornea of neurotrophins and Semaphorin 7A (SEMA7A), which are secreted into tears, and
neuropeptides in the trigeminal ganglia (TG) of a mouse model. Our objective will be to define the cascade of
molecular events that conduct the corneal nerve regeneration stimulated by PEDF+DHA. Our central
hypothesis is that PEDF+DHA, through specific docosanoids, activates selective gene programs and
modulates the inflammatory response that in turn, induces the nerve regeneration that leads to
preservation of corneal integrity. We will employ: 1) PEDF-receptor (PEDF-R) knockout (KO) mice and in
vivo models of corneal injury relevant to the clinical setting; 2) microfluidic chambers for co-culture of TG
neurons and corneal epithelial cells to define the molecular mechanism of neurite outgrowth; 3) LC-tandem
mass spectrometry lipidomic analysis to identify and quantify the incorporation of DHA in membrane
phosphatidylcholine molecular species and DHA-derivatives NPD1, RvD6 and other docosanoids; 4) flow
cytometry and our immunostaining assays to determine content of lymphocytes, dendritic cells, macrophages
and neutrophils; 5) immunostaining to quantify corneal nerves; 6) behavioral measurements of ocular
sensation to assess the functionality of the regenerated nerves; and 7) molecular biology techniques, including
gene editing to study the role of the different genes involved in the signaling of nerve regeneration activated by
PEDF+DHA and docosanoids. The proposed studies target new molecular mechanisms to understand and
treat complications due to corneal nerve damage. Our innovative approach will define agents for neurotrophic
keratitis and dry eye after refractive surgery.

## Key facts

- **NIH application ID:** 9903357
- **Project number:** 5R01EY019465-10
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** Haydee E.P. Bazan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $365,000
- **Award type:** 5
- **Project period:** 2009-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9903357

## Citation

> US National Institutes of Health, RePORTER application 9903357, Lipid Mediators in Corneal Nerve Regeneration (5R01EY019465-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9903357. Licensed CC0.

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