# Ocular surface applications of Descemet's membrane

> **NIH NIH K08** · UNIVERSITY OF MINNESOTA · 2022 · $241,950

## Abstract

PROJECT SUMMARY/ABSTRACT
Limbal stem cell (LSC) deficiency is a blinding disease that accounts for an estimated 15-20% of corneal
blindness worldwide. LSC deficiency is caused by excessive loss of LSC, a population of pluripotent cells that
regenerate the transparent corneal epithelium. Loss of LSC due to chemical injuries and autoimmune disease
results in corneal conjunctivalization, erosions, and melting. Treatment options are limited; however, cultured
limbal epithelial cell transplantation (CLET) is a promising emerging therapy. In CLET ex vivo expanded limbal
stem/progenitor cells (LSPC) are transplanted onto diseased eyes to replace the native LSC and regenerate the
corneal epithelium. Short-term success has been reported with CLET; however, long-term outcomes have been
limited by loss of transplanted LSPC and recurrence of LSC deficiency over time. One reason for this is the lack
of a supportive niche. Under physiological conditions, the microenvironment of the limbus, known as the limbal
niche, sustains the pluripotency and proliferative potential of native LSC. However, in LSC deficiency, the limbal
niche is often damaged. Identification of synthetic and biological substrates that can function as niche substitutes
to support transplanted LSPC remains an ongoing challenge and an unaddressed barrier to long-term success
in regenerative therapies for the ocular surface. Although human amniotic membrane (HAM) is the primary
substrate used for CLET, it is limited as a long-term niche substitute by its opacity, rapid degradation, and lack
of limbus-specific proteins. In contrast Descemet’s Membrane (DM), is a basement membrane on the posterior
surface of the cornea is clear and resistant to collagenase digestion. Furthermore, the anterior fetal banded layer
of DM is rich in limbus-specific basement membrane proteins, including collagen IV α1, α2 subtypes, vitronectin,
and BM40/SPARC. The goal of this study is to compare the stemness and survival of donor and iPSC-derived
LSPC on DM vs HAM. In aim 1, we will perform in vitro phenotypic and functional comparisons of LSPC cultured
on DM vs HAM using biomarker expression and an organ culture model of LSC deficiency. In aim 2, we will
perform an in vivo comparison of cultured LSPC on DM vs HAM using a mouse model of LSC deficiency. In aim
3, we will compare biomarker expression and capacity to regenerate corneal epithelium in iPSC-derived LSPC
cultured on DM vs HAM. This project has the potential to inform our choice of substrate in CLET and improve
our therapies for LSC deficiency. The training plan will provide the applicant with technical competencies in the
characterization of LSPC, use of animal models of LSC deficiency, and manipulation of iPSC; as well as
professional skills in oral and written communication to facilitate development as an independent investigator.
Training will take place in University of Minnesota’s (UMN) highly collaborative and well-resourced research
environment. The ap...

## Key facts

- **NIH application ID:** 10448019
- **Project number:** 1K08EY032097-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Joshua H Hou
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $241,950
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448019

## Citation

> US National Institutes of Health, RePORTER application 10448019, Ocular surface applications of Descemet's membrane (1K08EY032097-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10448019. Licensed CC0.

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