# DICER1 deficiency in aberrant chorioretinal neovascularization - Administrative Supplement OKT Request

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2022 · $60,245

## Abstract

SUMMARY/ABSTRACT
Aberrant ocular neovascularization contribute to blindness in numerous conditions including age-related macular
degeneration (AMD), diabetic retinopathy, and retinopathy of prematurity. DICER1 is a RNase that processes
micro-RNAs and SINE RNAs. Deficiency of DICER1 is implicated in outer retinal pathologies, including choroidal
neovascularization. This claim is supported by recently published studies finding that multiple models of DICER1
deficiency develop aberrant choroidal neovascularization in mice, and new evidence that DICER1 expression is
significantly reduced in human neovascular AMD. However, major gaps in knowledge persist with respect to the
relative contributions of major DICER1 substrate classes micro-RNA and SINE RNA imbalances as contributors
to choroidal neovascularization. In addition, whether DICER1 deficiency impedes conventional gene silencing
strategies, and the role of DICER1 in age-related neovascular pathologies are unknown. The overall hypothesis
of this project is that age-related DICER1 deficiency drives chorioretinal neovascularization via SINE RNA
accumulation and impedes conventional gene silencing strategies. We will test this hypothesis in three specific
aims. 1) We will distinguish between the contributions of micro-RNA and SINE RNA-dependent processing
activities of DICER1 with respect to development and severity of CNV. 2) We will adapt DICER1-independent
gene silencing strategies and compare them to traditional DICER1-dependent strategies in models of CNV. 3)
We will quantify DICER1 in aging retina, and determine whether ectopic DICER1 expression improves CNV
outcomes in aged animals. Collectively, these thematically related, but independent aims will establish new
foundational and translationally relevant knowledge about the mediators and consequences of DICER1
deficiency in pathological choroidal neovascularization. These studies may thereby open new interventional
avenues for prevalent blinding conditions.

## Key facts

- **NIH application ID:** 10647413
- **Project number:** 3R01EY032512-02S1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Bradley David Gelfand
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $60,245
- **Award type:** 3
- **Project period:** 2021-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10647413

## Citation

> US National Institutes of Health, RePORTER application 10647413, DICER1 deficiency in aberrant chorioretinal neovascularization - Administrative Supplement OKT Request (3R01EY032512-02S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10647413. Licensed CC0.

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