# Role of Primary Cilia-mediated Signaling in Development and Regeneration of the Meibomian Glands

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2020 · $245,625

## Abstract

Dry eye disease (DED) is a common, multifactorial disease with a global prevalence ranging from 5 to 50%.
Meibomian gland dysfunction (MGD) is considered the leading cause of DED. Meibomian glands (MG) are
modified sebaceous glands which line the margin of the eyelid and secrete lipids at the ocular surface and
participate to increase the stability of the tear film. MG are holocrine glands, which implies that they are
continually renewed since they deliver their secretory product, called meibum, by apoptosis. Thus, regulation of
MG stem cells is crucial to ensure proper function of MG. Currently, a significant hurdle in developing effective
treatments to cure MGD is that the basic cellular mechanisms underlying the development and the stem cell-
dependent maintenance of the MG are poorly understood. Interestingly, MG development shares similarities with
the development of the pilosebaceous unit where primary cilia, and the hedgehog (HH) pathway play essential
roles in hair follicle (HF) development and in maintaining a stem cell niche.
Our preliminary data, using the mouse as a model system, mouse provide strong evidence that the cilium and
the HH pathway play distinct roles during normal development of the MG. We found that the HH activity is high
during early developmental stages of the MG. However, the number of HH responsive cells in the MG decreases
as development progresses. In the adult, HH activity was detected in isolated cells of the acini and in the MG
excretory duct. Moreover, we found that while inactivation of the HH pathway via SMO deletion abolishes or
impairs the formation of MG, the deletion of IFT88, which prevents cilia formation, leads to hypertrophic MG.
The objective of the proposed study is to elucidate the function of the primary cilium and the HH signaling
pathway during the development and renewal of the MG with the long-term goal to identify new therapeutic
targets to promote MG renewal. To address these issues, we have generated specific genetic tools and
developed a 3D imaging analysis approach that will allow us to: a) To study the localization of ciliated and HH
responsive cells in the context of Meibomian gland development and homeostasis. b) To elucidate the role of
the HH pathway and the primary cilium during MG development and homeostasis. The outcome of this work will
reveal the integrative role of primary cilia signaling necessary to achieve normal MG morphogenesis. Importantly,
delineation of the cilia-related signaling cascades will enable the identification of new therapeutic strategies to
treat DED.

## Key facts

- **NIH application ID:** 10057624
- **Project number:** 1R21EY030661-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Carlo Iomini
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $245,625
- **Award type:** 1
- **Project period:** 2020-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057624

## Citation

> US National Institutes of Health, RePORTER application 10057624, Role of Primary Cilia-mediated Signaling in Development and Regeneration of the Meibomian Glands (1R21EY030661-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10057624. Licensed CC0.

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