# Role of MRTF signaling in proliferative vitreoretinopathy

> **NIH NIH R01** · UNIVERSITY OF LOUISVILLE · 2021 · $121,507

## Abstract

Project Summary/Abstract
Proliferative vitreoretinopathy (PVR) is a fibrotic complication affecting the retina. In PVR, loss of visual
acuity, and in severe cases blindness, is caused by contraction of scar tissue that form on the retinal
surface. PVR is found in ~50% of posterior segment ocular trauma cases and about 5% of cases after
surgical repair of rhegmatogenous retinal detachment. Reliable treatment for PVR is currently unavailable,
and therefore, prevention is important. The overall goal of this project is to unravel molecular mechanisms
involved in PVR development to identify targets for potential intervention. The trigger for fibrosis such as
PVR is sustained presence of myofibroblasts, a cell type specialized ECM deposition and wound
contraction. Recent studies show that stiff ECM activates intracellular signaling essential for differentiation
of myofibroblasts. Myofibroblasts, in turn, feeds back to further enhances ECM stiffness via aberrant ECM
deposition and crosslinking. This positive feedback loop between myofibroblasts and ECM rigidity sustains
myofibroblast presence, and its inhibition successfully prevented lung and liver fibrosis in animal models.
However, the underlying detailed mechanisms and molecules involved are both tissue and cell type
dependent, and the role of this positive feedback loop is yet to be examine in PVR. Past studies show the
presence of molecules involved in ECM stiffening in samples from PVR patients. Our preliminary data show
two key molecules known to be affected by ECM stiffness, transient receptor potential vanilloid 4 (TRPV4)
channel and myocardin-related transcription factor (MRTF), are required for myofibroblast
transdifferentiation of retinal pigment epithelial (RPE) and Müller glia cells, two resident cell types that give
rise to myofibroblasts in PVR. Further, data also show another molecule regulated by stiffness and known to
alter MRTF target expression, TAZ, interacts with MRTF. We propose studies to determine molecular
mechanisms activated by ECM stiffness leading to myofibroblast differentiation and PVR. In Aim1, the effect
of ECM stiffening molecules on myofibroblast differentiation and PVR will be examine. Detailed molecular
mechanism of regulating MRTF, which is key to myofibroblast differentiation, by TRPV4 and TAZ will be
determined in Aim2 and 3, respectively. The project has the potential to uncover key molecular therapeutic
targets for the prevention of PVR, and possibly other fibrotic diseases.

## Key facts

- **NIH application ID:** 10073515
- **Project number:** 5R01EY030060-02
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Shigeo Tamiya
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $121,507
- **Award type:** 5
- **Project period:** 2020-01-01 → 2021-06-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10073515

## Citation

> US National Institutes of Health, RePORTER application 10073515, Role of MRTF signaling in proliferative vitreoretinopathy (5R01EY030060-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10073515. Licensed CC0.

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