# Live imaging of stem cell dynamics in cornea regeneration

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $405,105

## Abstract

ABSTRACT
According to the World Health Organization 70 million people are visually impaired worldwide due to corneal
related diseases and injuries. In the U.S. alone more than 50,000 corneal transplants are performed annually
due to lack of alternative treatments. The cornea relies on resident stem cells to sustain vision and efficiently
regenerate after injury. Conditions that cause stem cells to deviate from their normal activity lead to corneal
disease. Elucidating the identity and mechanism of regulation of corneal stem cells is critical for devising new
effective treatments for corneal pathologies. We currently have incomplete knowledge of the stem cell
dynamics and regulation in the live cornea. A major roadblock is the inability to visualize directly single cell
activity during corneal regeneration to elucidate the precise contribution of stem cells. To overcome this, we
have pioneered a novel approach to visualize and track stem cell activity in the intact cornea of live mice by 2-
photon microscopy. The overall goal of this project is to implement an integrative approach by combining our
live imaging system with state-of-the-art optogenetic and genomic tools to 1) characterize stem cell dynamics,
2) identify intrinsic and extrinsic regulators of stem cell activity and 3) test their requirements for corneal
regeneration. In live imaging experiments of the cornea we found that stem and progenitor cells in the self-
contained corneal epithelium proliferate and differentiate in topologically diverse patterns during homeostasis
and wound healing. We hypothesize that the cornea consists of a heterogeneous population of stem cells with
distinct contributions to homeostatic maintenance and injury repair. Aim I of this proposal is designed to
resolve the specific contributions of stem cells and their immediate progeny to corneal regeneration and to test
their necessity for wound healing. Aim I will also address the role of key molecular signals in regulating the fate
of distinct epithelial populations within the cornea. Such signals can potentially be exploited for therapeutic
purposes. Aim II will investigate extrinsic regulation of corneal stem cells. The subbasal nerve plexus is a
major component of the corneal tissue environment. Our live imaging approach is ideal for studying the
functional interactions between the corneal nerves and the epithelium. We have devised in vivo assays for
visualizing and manipulating nerve processes in the live cornea. Aim II will test the requirement of the subbasal
nerve plexus for epithelial function in homeostasis and wound healing and explore novel mechanisms for
corneal nerve regeneration. These data will enable new therapies for patients with Neuropathic Keratitis. This
research is innovative because it uses cutting-edge imaging technologies and genetic tools to study stem cells
within the natural tissue environment of the live mammalian eye. Our goal is to uncover the fundamental
mechanisms of corneal reg...

## Key facts

- **NIH application ID:** 10000103
- **Project number:** 5R01EY030599-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Panteleimon Rompolas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $405,105
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000103

## Citation

> US National Institutes of Health, RePORTER application 10000103, Live imaging of stem cell dynamics in cornea regeneration (5R01EY030599-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10000103. Licensed CC0.

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