# Modeling and mechanistic investigation of a novel dry AMD mouse model with CLIC4 deleted in RPE

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $411,038

## Abstract

SUMMARY
Aged-related macular degeneration (AMD) is a complex disease and the leading cause of
blindness among the elderly. Dry AMD has unclear etiology and no treatment. Lipid-rich drusen
deposits are the silent hallmark of dry AMD. The retinal pigment epithelium (RPE) is likely to be
the primary lesion site of AMD. Lacking an AMD mouse model is a roadblock to advance this
research field. Recently we showed that RPE-specific CLIC4 knockout (KO) mice develop a full
spectrum of AMD-like pathophysiology, including the impaired visual function, the drusen-like
deposition, and severe RPE cell loss. CLIC4 is a redox-sensing pleiotropic protein. Our
characterizations showed CLIC4 deficiency alters a myriad of signaling pathways that are
required for maintaining RPE homeostasis. In particular, CLIC4-KO RPE cells had profound lipid
dysregulation. We proposed two specific aims to understand CLIC4's role in coupling several
aspects of the lipid homeostasis-metabolism, storage, and transport. We will investigate the lipid
homeostasis of the RPE in the context of cell biology. The overarching goal is to learn how
integrated outcomes as a consequence of loss-of-CLIC4 present the AMD-like pathophysiology.
We will investigate CLIC4’s role in the phospholipid (Aim1) and sphingolipid (Aim2) homeostasis
of RPE (Aim1) in the aspects of the lipid metabolism, storage, and transport. We will use
interdisciplinary approaches and state-of-the-art techniques (e.g., Imaging Mass Spectrometry-
LC/MS-MS lipidomics, transcriptomes, 3D electron microscopy) to studies these questions both
in vivo and in vitro. The obtained information will significantly advance our comprehension of the
basic science of the RPE and AMD etiology. They also have a strong potential for discovering
new drug targets to treat AMD.

## Key facts

- **NIH application ID:** 10475752
- **Project number:** 5R01EY032966-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** CHING-HWA SUNG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $411,038
- **Award type:** 5
- **Project period:** 2021-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475752

## Citation

> US National Institutes of Health, RePORTER application 10475752, Modeling and mechanistic investigation of a novel dry AMD mouse model with CLIC4 deleted in RPE (5R01EY032966-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10475752. Licensed CC0.

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