# Functional and therapeutic roles of the Hedgehog signaling in meibomian glands development, renewal and dysfunction

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $441,822

## Abstract

Meibomian gland disease (MGD) is considered the leading cause of dry eye disease, a common multifactorial
disease with a global prevalence of 5 to 50% and a major age-related disease of the ocular surface. Meibomian
glands (MG) are modified sebaceous glands that line the margin of the eyelid, secrete lipids at the ocular surface,
and participate in increasing the stability of the tear film. MGs are holocrine glands, which implies they are
continually renewed since they deliver their secretory product, called meibum, by apoptosis. Thus, regulation of
MG stem cells is crucial to ensure the proper function of MGs. With the aging process or disease condition, MGs
can progressively lose their renewal capability and regress to an atrophic state. The pathogenesis of MGD and
the mechanisms by which aging affects the renewal process remain largely unknown. Treatment options are
currently limited mainly due to the lack of clear therapeutic targets and effective drug delivery strategies targeting
the tissue of MGs. Thus, there is a critical need to understand signaling cascades underlying the renewal process
of the MG that can be pharmacologically targeted to treat MGD. Our recent advances, with the aid of an NIH/NEI
R21 (EY030661), have led us to discover a novel role of the primary cilium in MG development and maintenance
suggesting a role of HH in the this process. The Hedgehog (HH) pathway plays a fundamental role in tissue
development, homeostasis, and repair, including adult stem cell maintenance. To determine the therapeutic
potential of targeting the HH pathway to treat MGD, we will investigate its role in MG development, maintenance,
and renewal and trace the cell lineage of HH-responsive cells involved in MG homeostasis. We will target the
HH pathway in mice using genetic and pharmacological HH modulators to improve age-related MGD. If
successful, the outcome of this work will reveal mechanistic insights into MG renewal and define a novel
paradigm for how to approach novel treatment strategies for MGD.

## Key facts

- **NIH application ID:** 10859607
- **Project number:** 1R01EY036135-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Carlo Iomini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $441,822
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10859607

## Citation

> US National Institutes of Health, RePORTER application 10859607, Functional and therapeutic roles of the Hedgehog signaling in meibomian glands development, renewal and dysfunction (1R01EY036135-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10859607. Licensed CC0.

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