# Pathogenesis of Uveitis in Ebola Virus Disease Survivors

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2022 · $495,989

## Abstract

Project Summary/ Abstract
Ebola virus disease (EVD) has been associated with a high prevalence of uveitis in EVD survivors in the wake
of the unprecedented West African EVD outbreak from 2014-2016. The spectrum of disease ranges from
anterior uveitis to sight-threatening panuveitis with complete blindness. The sheer number of EVD survivors
impacted has given us the unique opportunity to characterize the clinical features, structural complications
leading to vision loss, and pathogenesis of uveitis. Besides the significant impact of vision loss on quality-of-
life and activities of daily living, uveitis associated with Ebola virus (EBOV) has scientific and public health
implications because of our prior identification of EBOV in the aqueous humor. Beyond the recent outbreak in
West Africa, two more recent outbreaks in Democratic Republic of Congo underscore the global health
mandate to fully understand the clinical and scientific implications of EVD sequelae.
Emerging clinical, basic, and translational investigation has provided insight regarding the potential
mechanisms of uveitis associated with EVD. We recently described our novel methodology to safely
interrogate aqueous humor specimens for EBOV in EVD survivors; while these ocular fluid specimens tested
negative for EBOV by RT-PCR, recent molecular pathologic analysis of ocular tissue in a non-human primate
EVD survivor model has demonstrated that EBOV persists within the vitreous humor in macrophages, and is
associated with uveitis and retinitis. Additional compelling immunologic studies of an EVD survivor with uveitis
showed Ebola-specific T-cell and B-cell activation with signs of ongoing Ebola antigen stimulation after plasma
clearance of EBOV. These findings were suggestive of long-term EBOV persistence, which are detectable by
systemic T- and B-cell responses. To further characterize the prevalence and clinical spectrum of uveitis, role
of EBOV persistence and immunologic mechanisms of uveitis in EVD survivors, we propose three Aims:
1) In Aim 1, the prevalence of uveitis will be compared between EVD survivors and close contacts in Sierra
Leone. Clinical factors and host risk factors including HLA-typing will be assessed to determine if there are
clinical and host-related determinants of uveitis development.
2) In Aim 2, EBOV persistence will be assessed using reverse transcriptase polymerase chain reaction (RT-
PCR testing) of vitreous fluid and in situ hybridization techniques to detect EBOV genome in the vitreous.
3) In Aim 3, Ebola-specific immune responses will be assessed in the blood and ocular fluid of EVD survivors
with uveitis, specifically evaluating activation of Ebola-specific B and T-cells, IgG subclass composition.
Insights from this study will define the spectrum of uveitis associated with EVD, assess whether EBOV is
harbored in the vitreous, and advance our understanding of the interplay between infection and immunity in
EVD. Ultimately, these findings will define diagn...

## Key facts

- **NIH application ID:** 10490254
- **Project number:** 5R01EY029594-05
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Steven Yeh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $495,989
- **Award type:** 5
- **Project period:** 2019-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490254

## Citation

> US National Institutes of Health, RePORTER application 10490254, Pathogenesis of Uveitis in Ebola Virus Disease Survivors (5R01EY029594-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10490254. Licensed CC0.

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