# Determinants of Lens Fiber Cell Structure

> **NIH NIH R21** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $188,442

## Abstract

PROJECT SUMMARY/ABSTRACT
The primary function of the lens is to focus light on the retina so as to allow us to see. This function relies on
the transparency of the lens, and this transparency depends on the precise organization of its primary
constituent cell type, the lens fiber cells. Our goal is to understand what determines the correct cellular
organization within the lens that confers its transparency. As lens fiber cells differentiate, they elongate and
make direct interactions between themselves to create a highly ordered, tissue-wide cellular organization that
confers the overall architecture of the tissue and its transparency. Any disruption of this organization leads to
opaque lenses (i.e. cataracts) that are the most common cause of blindness world-wide. We recently
discovered two proteins that dictate lens architecture: they are Dlg-1 and Scrib1. Furthermore, we determined
that Dlg-1 is critical for conferring planar cell polarity (PCP) in mice. PCP refers to the coordination of cells
such that they move, orient, and/or proliferate in a particular direction critical for the normal morphogenesis of
the relevant tissue. Another core PCP protein, Vangl2, has been implicated in determining lens shape. Here
we provide evidence that Scrib as well as the newly identified PCP protein, Dlg-1, and the well-established
PCP protein, Vangl2 determine overall lens architecture. They do so by determining the overall shape of lens
fiber cells, and the cell:cell contacts between lens fiber cells within the equatorial region of the lens. Unclear is
whether this is due to PCP-dependent or PCP-independent effects of these proteins on lens architecture. The
primary goal of this exploratory R21 grant application is to distinguish between these two possibilities. We will
approach this using genetic approaches that have been well-validated in other invertebrates as well as more
detailed mechanistic studies including the use of state-of-the-art high resolution STED microscopy to resolve
the interactions between core PCP proteins and other factors involved in determining lens shape. The two
aims of this R21 proposal are to 1) Determine whether planar cell polarity is key to determining lens
architecture and 2) Define the interplay between planar cell polarity factors and cell:cell adhesion factors in
determining lens architecture. Completion of these studies will provide important and novel insights into the
mechanisms required to achieve and maintain lens transparency, a research priority of the NEI, and have an
impact on the overarching NEI goal of better preventing and treating cataracts.

## Key facts

- **NIH application ID:** 10145003
- **Project number:** 5R21EY030604-02
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** ANNE E GRIEP
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $188,442
- **Award type:** 5
- **Project period:** 2020-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145003

## Citation

> US National Institutes of Health, RePORTER application 10145003, Determinants of Lens Fiber Cell Structure (5R21EY030604-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10145003. Licensed CC0.

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