# DICER1 deficiency in aberrant chorioretinal neovascularization

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $510,360

## Abstract

Abstract/Summary
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:** 10892033
- **Project number:** 5R01EY032512-04
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Bradley David Gelfand
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $510,360
- **Award type:** 5
- **Project period:** 2021-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892033

## Citation

> US National Institutes of Health, RePORTER application 10892033, DICER1 deficiency in aberrant chorioretinal neovascularization (5R01EY032512-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10892033. Licensed CC0.

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