# Reversing Contractility in Epiretinal Membranes

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $422,502

## Abstract

While much is known on the causes of epiretinal membrane formation in retina diseases such as 
Proliferative Vitreoretinopathy (PVR) and Proliferative Diabetic Retinopathy (PDR), the progression 
of cell transformation into myocontractile phenotype and the machinery responsible for the 
contraction is less understood. The long-term goal is that when a membrane in patients with 
Proliferative Vitreoretinopathy or Proliferative Diabetic Retinopathy is identified we have an 
understanding of the contraction machinery responsible and can prescribe treatments to stop or 
reverse membrane contraction. The objective of this proposal is to determine the components of the 
contraction machinery that are essential for membrane contraction. The central hypothesis is 
contraction associated genes we identify during whole transcriptome sequencing of patient 
epiretinal membranes are components of the contraction machinery are responsible for membrane 
contraction and retinal detachment in patients with PVR and PDR. The rational underlying this 
proposal is that completion will identify key physical targets that when disabled will prevent or 
reverse membrane contraction. The central hypothesis will be tested by pursuing two specific aims: 
1) To determine the mechanisms underlying the transformation of retinal pigment epithelium (RPE) 
into a contracting membrane. 2) To identify contraction-associated genes in the membranes from 
patients with PVR and PDR and evaluate their necessity for contraction by retinal cells in a new 
model of membrane contraction and a well established animal model. We will pursue these aims using 
an innovative combination of analytical and manipulative techniques. These include using the 
protocol we designed to isolate RNA from patient dissected membranes with sufficient yield and 
quality enabling whole transcriptome sequencing. Additionally we will use retina cell culture 
methods and a new model of contraction developed by this team that enables the preservation of 
native physiology and resembles the disease contraction phenotype. We will use these new methods in 
tandem with well-established techniques in molecular biology. The research proposal is significant, 
because the results will identify the machinery responsible for retinal membrane contraction and 
vision loss in PVR and PDR. From this understanding, new therapeutic approaches may be developed 
for rescuing patients from vision loss. The expected outcome of this work is a more complete 
understanding of retinal membrane formation and contraction in two devastating eye diseases, which 
will provide insight into other fibrotic membrane diseases of the retina. The results will have a 
positive impact immediately as the new knowledge gained will point to new targets for the 
prevention of vision loss.

## Key facts

- **NIH application ID:** 10828762
- **Project number:** 5R01EY029736-05
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Timothy A. Blenkinsop
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $422,502
- **Award type:** 5
- **Project period:** 2020-06-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10828762

## Citation

> US National Institutes of Health, RePORTER application 10828762, Reversing Contractility in Epiretinal Membranes (5R01EY029736-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10828762. Licensed CC0.

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