# Structural, mechanical, and cell biological properties of the ciliary zonule

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $477,830

## Abstract

Project Summary
The fibers of the ciliary zonule suspend the lens on the optical axis and transmit the forces that flatten it during
disaccommodation. Mutations in genes encoding zonular proteins underlie syndromic and non-syndromic
conditions that affect the eye profoundly. Common ocular phenotypes include ectopia lentis (lens dislocation),
cataract, axial elongation, myopia, glaucoma, and retinal detachment. The molecular composition of the zonule
was recently elucidated, but the mechanism by which mutations in zonular components culminate in structural
failure of the fibers is unknown. In Aim 1, therefore, three zonulopathies (Marfan Syndrome, Weill-Marchesani
Syndrome, and Isolated Ectopia Lentis) will be modeled in mice. Utilizing recently developed imaging and
material testing techniques, we will examine how, in each case, the structure and viscoelastic properties of the
mouse zonule are affected by the presence of the mutant protein (or absence of the wild-type protein). We
hypothesize that the initial pressurization of the eye is a critical step in zonule development. In Aim 2, this
notion will be tested by measuring the rise in intraocular pressure in postnatal mice and determining whether
pressurization of the developing eye in vitro causes precocious deployment of zonular fibers. Preliminary
studies identified the cross-linking enzyme lysyl oxidase-like-1 (LOXL1) as an abundant component of the
zonule proteome. In Aim 3, we propose that LOXL1-derived cross-links have a critical role in strengthening the
zonule. We will test that hypothesis in a knockout mouse model. Finally, microspherophakia (i.e., the presence
of a smaller and more spherical lens) is observed in Weill-Marchesani patients (who harbor mutations in
LTBP2 or FBN1, zonular proteins that contribute to the tensile properties of the fibers). We hypothesize that
forces exerted by the zonular fibers on the lens surface influence lens growth. In Aim 4, we will elucidate the
three dimensional structure of the human zonule and correlate the distribution of proliferating lens epithelial
cells with the strain fields established around zonular attachment points.

## Key facts

- **NIH application ID:** 10783775
- **Project number:** 5R01EY029130-06
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Steven Bassnett
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $477,830
- **Award type:** 5
- **Project period:** 2018-06-01 → 2028-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10783775

## Citation

> US National Institutes of Health, RePORTER application 10783775, Structural, mechanical, and cell biological properties of the ciliary zonule (5R01EY029130-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10783775. Licensed CC0.

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