# Exploring novel modulators for rescuing cigarette smoke-induced corneal edema and examining iPSC-derived corneal endothelial cells as a treatment modality

> **NIH NIH K99** · JOHNS HOPKINS UNIVERSITY · 2024 · $90,178

## Abstract

Project Summary
Cigarette smoke (CS) is a complex mixture of toxins (e.g., nicotine, carbon monoxide) that
affects multiple tissues of the eye including the cornea, the outermost tissue of the eye. The
cornea is at high risk due to its proximity to the burning end of the cigarette and flying ash.
Corneal endothelium (CE) is the innermost layer of the cornea responsible for corneal hydration.
CS results in progressive corneal endothelial cell (CEC) loss leading to corneal edema and
vision loss if remains untreated. The severity of CS-induced corneal edema is further
compounded with preexisting morbidities such as corneal endothelial dystrophies and diabetes.
Our preliminary studies of proteome profiling have demonstrated that CS triggers CEC loss and
disruption of critical structural proteins in Descemet’s membrane (DM). We further identified
elevated levels of oxidative stress-associated indicators and decreased levels of CE-associated
markers in response to cigarette smoke extract (CSE) treatment in human induced pluripotent
stem cell (iPSC)-derived CEC monolayer cultures. In parallel, we have shown that human
embryonic stem cell (hESC)-derived CECs can form a functional CE on denuded DM (DM
without CE) in rabbits and monkeys. Moreover, we have also shown that injected hESC-derived
CECs can form a functional CE on denuded stroma (stroma without CE and DM).
In this application, we will build on these datasets through large-scale screening of cellular
pathway modulators to establish a non-invasive topical eye drop approach. In parallel, we will
demonstrate the efficacy of the iPSC-derived CECs injection technique as a minimally invasive,
donor tissue-independent, treatment modality. Taken together, the combined knowledge gained
from identifying modulators and cell therapy will make a paradigm by offering an unlimited
source for the treatment of oxidative stress-induced CE disorders.

## Key facts

- **NIH application ID:** 10929452
- **Project number:** 5K99EY035363-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Muhammad Ali Riaz
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $90,178
- **Award type:** 5
- **Project period:** 2023-09-30 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10929452

## Citation

> US National Institutes of Health, RePORTER application 10929452, Exploring novel modulators for rescuing cigarette smoke-induced corneal edema and examining iPSC-derived corneal endothelial cells as a treatment modality (5K99EY035363-02). Retrieved via AI Analytics 2026-06-09 from https://api.ai-analytics.org/grant/nih/10929452. Licensed CC0.

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