# Immunopathogenesis of Adenovirus Keratitis

> **NIH NIH R01** · MASSACHUSETTS EYE AND EAR INFIRMARY · 2022 · $237,819

## Abstract

PROJECT SUMMARY
Conjunctivitis, a common ocular condition with a range of etiologies, is highly prevalent, affecting
approximately 6 million people annually in the United States, accounting for 1% of all primary care office
visits, and costing 430 million USD annually. Viruses are responsible for ~ 80% of conjunctivitis cases,
and human adenoviruses (HAdVs) are implicated in up to 65%. A particularly severe variant of
adenoviral conjunctivitis, epidemic keratoconjunctivitis (EKC) is caused principally by viruses within
human adenovirus species D (HAdV-D), for example the highly virulent adenovirus type 37. The clinical
manifestations of EKC include severe membranous conjunctivitis and epithelial keratitis, followed by
delayed onset of multifocal subepithelial (stromal) corneal infiltrates that cause light sensitivity and
reduced vision and can persist or recur for months to years after the acute infection. We have shown
previously that acute HAdV-D infection of human keratocytes induces intracellular signaling and robust
expression of neutrophil and monocyte chemokines, and that physical components of the adenovirus
(viral capsid and DNA) initiate molecular pattern responses in the corneal stroma. However, why
adenovirus keratitis can be chronic and recurrent when the infection has resolved and the adenovirus
is no longer present has not been previously studied. The specific aims of this proposal are to test the
hypotheses that 1) the post EKC cornea expresses a unique array of pro-inflammatory mediators, 2)
the post EKC cornea retains innate immune cells with a chronically altered transcriptome, and 3) long-
lasting pro-inflammatory changes in the post EKC cornea can be mitigated by epigenetic modifying
agents. We will study the cornea in our adenovirus mouse keratitis model after resolution of the
infection, using protein arrays and immuno-microscopy to elucidate the pro-inflammatory mediators
responsible for chronic adenovirus keratitis, flow cytometry and single cell RNA-seq to determine
infiltrating cellular phenotypes and individual cell type transcriptomes, and single cell ATAC-seq to
determine changes in cellular chromatin of resident keratocytes and infiltrating cells. Finally, we will
apply known modifying agents of cellular chromatin in an attempt to prevent, reduce, or reverse pro-
inflammatory mediator expression and pathologic innate immune cell phenotypes in chronic adenovirus
keratitis. These studies are designed to take us closer to our goal of effective information-based
therapies against HAdV eye infections. EKC is a common affliction, and the proposed study addresses
a major public health concern.

## Key facts

- **NIH application ID:** 10358683
- **Project number:** 2R01EY013124-20A1
- **Recipient organization:** MASSACHUSETTS EYE AND EAR INFIRMARY
- **Principal Investigator:** James Chodosh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $237,819
- **Award type:** 2
- **Project period:** 2001-06-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10358683

## Citation

> US National Institutes of Health, RePORTER application 10358683, Immunopathogenesis of Adenovirus Keratitis (2R01EY013124-20A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10358683. Licensed CC0.

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