# The Influence of Capsule Composition on Lens Biology

> **NIH NIH R01** · UNIVERSITY OF DELAWARE · 2022 · $391,792

## Abstract

Extracapsular cataract surgery is a marvel of modern medicine that has greatly reduced
the global burden of cataract-related blindness. However, optimal implantation of a
replacement intraocular lens requires preservation of most of the lens capsule, the basement
membrane surrounding the lens. Since lens epithelial cells (LECs) are tightly attached to the
lens capsule, it is not possible to remove all LECs during cataract surgery, and these cells
undergo robust wound healing responses characterized by cell proliferation and the
transdifferentiation of LECs to scar producing myofibroblasts. While modern intraocular lens
implants can sequester myofibroblasts away from the ocular axis short term, these cells can
survive long term at the periphery of the capsular bag, and often escape years after surgery,
migrating into the visual axis, where they can proliferate, wrinkle the capsule, and produce
fibrotic extracellular matrix molecules, leading to the onset of posterior capsular opacification
(PCO) years after the initial cataract surgery. Thus, understanding the mechanisms by which
myofibroblasts differentiate post lens injury, and maintain their phenotype long term is of great
importance. During the last grant cycle, we discovered that fibronectin produced by lens cells
after surgery was critical for the maintenance of the fibrotic phenotype of LECs post fiber cell
removal while RNAseq profiling revealed that numerous inhibitors of protease activity
upregulate their expression dramatically in LECs following lens injury suggesting a key role for
fibrotic ECM in establishing and sustaining fibrotic PCO. This proposal seeks to investigate the
molecular mechanisms by which fibronectin regulates the fibrotic phenotype of lens epithelial
cells and the role of matrix regulators in this process.

## Key facts

- **NIH application ID:** 10445385
- **Project number:** 2R01EY015279-18
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** MELINDA K DUNCAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $391,792
- **Award type:** 2
- **Project period:** 2003-12-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10445385

## Citation

> US National Institutes of Health, RePORTER application 10445385, The Influence of Capsule Composition on Lens Biology (2R01EY015279-18). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10445385. Licensed CC0.

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