# STRUCTURAL, MECHANICAL, AND CELL BIOLOGICAL PROPERTIES OF THE CILIARY ZONULE

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $379,552

## Abstract

Project Summary.
A system of extracellular fibers called the ciliary zonule suspends and centers the lens in the
eye. Breakage of zonular fibers is a characteristic of many ocular diseases and results in
dislocation of the lens (ectopia lentis). Mutations in genes encoding zonular proteins have
profound effects on ocular development. In addition to ectopia lentis, these include
microspherophakia and high axial myopia. These observations support the notion that the
zonule has a role in ocular development beyond merely positioning the lens on the optical axis.
To gain insights into the role of the zonule, we have developed mouse models in which the two
most abundant zonular proteins, fibrillin-1 (FBN1) and latent TGFbeta-binding protein 2 (LTBP2)
have been deleted. In both models, the zonule is synthesized initially, but over time, ectopia
lentis develops in all animals. Moreover, LTBP2-deficient mice have microspherophakia and
FBN1 deficient mice develop lens-induced glaucoma. We will utilize these murine models to
test the specific contributions of FBN1 and LTBP2 to the structure and biomechanical properties
of zonular fibers. We will also test the long-standing hypothesis that zonular tension modulates
the rate of cell proliferation in the germinative zone of the lens, thereby directly influencing lens
size. Together, these experiments will provide insights into the ocular phenotypes of human
patients with Marfan syndrome or Weill-Marchesani syndrome, heritable conditions arising from
mutations in FBN1 and LTBP2, respectively. Furthermore, because microfibrils (the sole
constituents of zonular fibers) are implicated in disease processes elsewhere in the body
(cardiovascular disease, for example) the results of structure/function studies performed on the
ciliary zonule are expected to have broad clinical relevance.

## Key facts

- **NIH application ID:** 9935064
- **Project number:** 5R01EY029130-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Steven Bassnett
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $379,552
- **Award type:** 5
- **Project period:** 2018-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935064

## Citation

> US National Institutes of Health, RePORTER application 9935064, STRUCTURAL, MECHANICAL, AND CELL BIOLOGICAL PROPERTIES OF THE CILIARY ZONULE (5R01EY029130-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9935064. Licensed CC0.

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