# Role of PDLIM1 in Retinal Vascular Leakage and Proliferation

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $237,544

## Abstract

Abstract
Retinopathy of Prematurity (ROP) is a potentially blinding condition of low birth weight premature children
that affects over 50,000 children worldwide each year. The incidence of ROP is on the rise, primarily due
to improvements in neonatal care in developing nations. The underlying pathophysiology of ROP is a
consequence of ischemia of the peripheral retina. Ischemia can lead aberrant neovascularization at the
border between the vascularized and non-vascularized retina. These vessels are incompetent and may
lead to edema, bleeding, fibrosis, and can ultimately progress to a tractional retinal detachment and
blindness. Importantly, parallel vascular changes are also responsible for visual morbidity in other
diseases of the retinal vasculature, including diabetic retinopathy (DR), which affects 25.8 million
Americans and is the leading cause of blindness in the working-age population. Changes in the function
of the retinal vascular endothelial cells, including neovascularization and vascular leakage, are central to
the disease phenotype, yet little is known about the molecular changes that occur in these cells that lead
to their dysfunction. To investigate these molecular changes, we have purified the vascular endothelial
cells during key timepoints in oxygen induced retinopathy (OIR), a mouse model of ischemic
vasculopathy, and evaluated the transcriptome. These data identified PDLIM1 as a molecule that is
upregulated specifically in the vascular endothelial cells at the time of leakage and proliferation. In tissue
culture, expression of PDLIM1 results in a reduction of the barrier properties. We have now generated
PDLIM1 knockout and overexpression mouse strains, and propose to test the role of PDLIM1 in retinal
vascular permeability and proliferation. This work may identify PDLIM1 as a novel therapeutic target to
prevent breakdown of the blood-retinal barrier and aberrant neovascularization in diseases of the retinal
vasculature.

## Key facts

- **NIH application ID:** 9902472
- **Project number:** 5K08EY028999-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Eric D Nudleman
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $237,544
- **Award type:** 5
- **Project period:** 2018-04-01 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902472

## Citation

> US National Institutes of Health, RePORTER application 9902472, Role of PDLIM1 in Retinal Vascular Leakage and Proliferation (5K08EY028999-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9902472. Licensed CC0.

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