# The mechanisms underlying posterior capsular opacification

> **NIH NIH R01** · UNIVERSITY OF DELAWARE · 2021 · $332,662

## Abstract

Extracapsular cataract surgery has greatly reduced the global burden of cataract-related
blindness. While this procedure is very effective, most patients develop significant ocular
inflammation after cataract surgery, which can compromise vision, while its treatment with
potent anti-inflammatory drugs is unpleasant for patients and can cause side effects. While
some inflammatory pathways activated by cataract surgery are known, these have not been
comprehensively profiled and their mechanisms of pathway induction are not known. Further,
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, not all LECs can be removed during cataract surgery, and
these cells tend to undergo robust wound healing responses. The resulting proliferation,
migration, transdifferentiation to myofibroblasts, and formation of aberrant lens fibers often
results in the formation of opaque plaques in the visual axis post-cataract surgery, resulting in
posterior capsular opacification (PCO), a common side effect of cataract surgery. While it is
known that myofibroblast formation in PCO requires the activation of TGFβ/SMAD pathways
post-surgery, there is a lag between the time of surgery and TGFβ pathway activation, likely
due to the need to both activate latent TGFβ, and to prime LECs to efficiently respond to this
signaling. However, little is known about the pathways triggered immediately after surgery
that lead to robust activation of TGFβ signaling necessary to form fibrotic PCO in vivo. This
application seeks to fill these knowledge gaps by investigating the molecular changes that occur
in LECs prior to the onset of robust TGFβ pathway activation in two specific aims. The first aim
investigates both the molecular mechanisms regulating ocular inflammation post-cataract
surgery and the subsequent onset of pro-fibrotic gene expression in the LECs remaining behind
after surgery while investigating how this remodeling of the the lens epithelial cell
transcriptome is regulated by "immediate early genes“ (IEGs). The second aim tests the
hypothesis that the canonical Wnt signaling that upregulates during the first day after cataract
surgery is functionally important in the pathogenesis of PCO and investigates its regulation by
IEGs. This investigation will fill the current gap in knowledge concerning the molecular
changes that occur between the time of surgery and robust TGFβ pathway activation leading to
PCO, a major side effect of modern cataract surgery.

## Key facts

- **NIH application ID:** 10247771
- **Project number:** 5R01EY028597-04
- **Recipient organization:** UNIVERSITY OF DELAWARE
- **Principal Investigator:** MELINDA K DUNCAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $332,662
- **Award type:** 5
- **Project period:** 2018-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10247771

## Citation

> US National Institutes of Health, RePORTER application 10247771, The mechanisms underlying posterior capsular opacification (5R01EY028597-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10247771. Licensed CC0.

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