# New strategies for prevention of posterior capsule opacification

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $385,000

## Abstract

PROJECT SUMMARY
 Posterior capsule opacification (PCO) is the most common and costly vision-disrupting complication of
cataract surgery. A stated major research priority of the Lens and Cataract Program at NEI is "to study the
mechanism of TGFβ−mediated lens fibrosis in order to develop effective means of preventing PCO." During
the past 25 years, we have perfected a serum-free primary chick lens cell culture system (DCDMLs) that has
been validated as an appropriate model for the mammalian lens. Using this system, we found that TGFβ can
induce not only lens cell fibrosis (i.e., epithelial-mesenchymal transition to myofibroblasts; EMyT), but also lens
fiber cell differentiation. The latter is a major cause of clinically deleterious PCO. In this application, we propose
three novel strategies to prevent PCO that target different pathways. Each has the potential to block the
development of fibrotic and/or lens fiber-type PCO without increasing the time, complexity, or cost of current
standard cataract surgery. They also provide new clinical applications for approved or investigational human
therapeutics, a goal of another NIH program (the drug repurposing/rescue initiative at NCATS).
 (1) We have made the unprecedented discovery that a small molecule multikinase inhibitor FDA-approved
in 2012 to fight leukemia blocks TGFβ-induced EMyT and lens fiber cell differentiation in DCDMLs, as well as
two other processes essential for the development of PCO (lens cell proliferation and migration). Effective
levels of this drug can be loaded into, and be released within an hour from, a standard human intraocular lens
(IOL), and were non-toxic in rabbits after either intracameral or intravitreal injection. Aim #1 is to assess the
ability of such drug-releasing IOLs to prevent PCO in the most commonly used and accepted preclinical animal
model for PCO, namely rabbits subjected to mock cataract surgery. These studies will be conduced in
collaboration with Dr. Liliana Werner, a worldwide authority on PCO and its preclinical assessment in rabbits.
 (2) We have recently discovered that 10/10 small molecule inhibitors of ErbB (EGF) family receptors block
TGFβ from inducing EMyT in DCDMLs. To our knowledge, these studies are the first to reveal an obligatory
cooperation between the TGFβ and ErbB pathways in fibrosis in lens cells. Aim #2 is to identify the ErbB
receptors and ligands required for this process, the essential first step in elucidating the molecular mechanisms
of this interaction. We will also test if an FDA-approved ErbB R inhibitor can be delivered via IOL.
 (3) An obvious but underappreciated consequence of cataract surgery is that the surviving anterior lens
epithelial cells loose almost all of their cell-cell contacts. In non-lens systems, two types of druggable
transcriptional effectors have been shown to regulate TGFβ-induced fibrosis in a cell density-dependent
manner. On the basis of preliminary evidence presented in this application, we propose t...

## Key facts

- **NIH application ID:** 9853795
- **Project number:** 5R01EY028558-03
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** LINDA S MUSIL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,000
- **Award type:** 5
- **Project period:** 2018-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853795

## Citation

> US National Institutes of Health, RePORTER application 9853795, New strategies for prevention of posterior capsule opacification (5R01EY028558-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9853795. Licensed CC0.

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