# Targeting Fibroblast Growth Factor Signaling as a New Therapeutic Strategy for Meibomian Gland Dysfunction

> **NIH NIH R21** · UNIVERSITY OF MISSOURI-COLUMBIA · 2020 · $247,291

## Abstract

PROJECT ABSTRACT
Dry eye disease (DED) is a multifactorial disease characterized by desiccation of the ocular surface, potentially
leading to permanent injury of the ocular surface and visual impairment. The most common cause of
evaporative DED is meibomian gland dysfunction (MGD) which is characterized by glandular atrophy and/or
ductal obstruction. Despite the high prevalence of MGD in DED, very little is known about its pathogenic
mechanisms, and no targeted and effective treatments exist to restore meibomian gland (MG) function.
Current treatments are mostly palliative and unsatisfactory, since they simply aim at symptomatic relief of DED,
not at the underlying cause of MGD. A major obstacle in developing new strategies for effective treatment of
MGD is the lack of an animal model that recapitulates MGD in humans. A unique mouse model of MGD has
been created in which fibroblast growth factor receptor 2 (Fgfr2) is depleted upon induction by doxycycline
(Dox). An advantage of this mouse model (referred as Fgfr2CKO ) is that gene deletion can be induced at
various stages of the animal’s life and the extent of gene deletion (and thus the extent of MG degeneration and
capacity of tissue regeneration) can be modulated by the dosage, or frequency, of doxycycline (Dox) induction
treatment. This capability provides a reproducible mouse model of MGD showing strong promise as a model
of MGD in humans. In this application, the preliminary studies in the Fgfr2CKO mice support the hypothesis that
the FGFR2-signaling pathway plays a critical role not only for MG homeostasis but also in glandular
regeneration in adult mice. Therefore, it is plausible that FGF ligand that can act on the FGFR2-signaling
pathways can prevent glandular atrophy and promote tissue regeneration, thus serving as MGD-specific
therapeutics to treat evaporative DED. The first specific aim of this application is to perform clinical
assessment and histopathological analysis of induced MG atrophy and spontaneous regeneration in Fgfr2CKO
mice. The outcome will provide the critical benchmarks for Aim 2. The second specific aim is to assess the
efficacy of targeting FGFR2 activity by FGF7 as a novel therapeutic strategy for MGD. These preclinical
studies in this new mouse model not only will identify potential therapeutic strategies for restoring MG function
but also will expand understanding of the pathogenesis of MGD in DED. More importantly, the proposed
therapeutic strategy of targeting FGF-signaling pathways has never been explored and may revolutionize the
clinical management of MGD.

## Key facts

- **NIH application ID:** 9896256
- **Project number:** 1R21EY029106-01A1
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Andrew J.W. Huang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $247,291
- **Award type:** 1
- **Project period:** 2020-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896256

## Citation

> US National Institutes of Health, RePORTER application 9896256, Targeting Fibroblast Growth Factor Signaling as a New Therapeutic Strategy for Meibomian Gland Dysfunction (1R21EY029106-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9896256. Licensed CC0.

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