# Mechanisms of Herpetic Keratitis

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE KNOXVILLE · 2020 · $448,710

## Abstract

SUMMARY
 Inflammatory events along the visual axis invariably impair vision and the eye itself employs maneuvers
to limit them, although not always successfully. For example, the most consequential outcome of ocular infection
with Herpes simplex virus (HSV) is a chronic inflammatory reaction in the corneal stroma (stromal keratitis-SK).
This lesion largely results from pro-inflammatory immune responses to infection which the host attempts to limit
by several counter-inflammatory maneuvers. A prominent component of counter-inflammation is the activity of
regulatory T cells (Treg), especially those that can be identified because they express the Foxp3 transcription
factor which controls their regulatory activity. When the Treg response is absent or impaired SK lesions are more
prolonged and consequential. Accordingly approaches that expand or increase the function of Treg represent
potentially valuable forms of therapy. Unfortunately, the function of Treg can be unstable with the cells
themselves losing their regulatory function and even taking on a pro-inflammatory role and then contributing to
tissue damage. This instability, usually referred to as plasticity, can occur when Treg are in an inflammatory
environment such as is usually the situation in SK. We anticipate that plasticity represents a problem during SK
which needs to be controlled with appropriate therapeutic procedures. In the present proposal experiments are
designed to formally demonstrate that Treg plasticity does occur in SK and to quantify its contribution to causing
tissue damage in the eye.
 We shall also evaluate the ability of several therapeutic procedures that may block or even reverse Treg
plasticity. A second series of experiments are designed to evaluate the therapeutic value of modifying the
expression of some key microRNA molecules that we anticipate influence the severity of SK lesions. Finally, one
aim of the proposal deals with the problem that during SK new blood vessel development occurs in the normally
avascular cornea and this facilitates access of inflammatory components to the cornea and interferes with vision.
A novel approach to control corneal neovascularization will be evaluated used as a single therapeutic approach
or along with approaches found optimal to control Treg plasticity and /or microRNA modulation.

## Key facts

- **NIH application ID:** 9852441
- **Project number:** 5R01EY005093-36
- **Recipient organization:** UNIVERSITY OF TENNESSEE KNOXVILLE
- **Principal Investigator:** Barry T. Rouse
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $448,710
- **Award type:** 5
- **Project period:** 1984-09-30 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852441

## Citation

> US National Institutes of Health, RePORTER application 9852441, Mechanisms of Herpetic Keratitis (5R01EY005093-36). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9852441. Licensed CC0.

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