# Dissecting the role of ELOVL2 in Drusen Biogenesis and Age Related Macular Degeneration

> **NIH NIH K08** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $241,085

## Abstract

ABSTRACT
The goal of this K08 grant is to allow Dr. Daniel Chao, M.D., Ph.D. to obtain the necessary scientific training
and professional skills to become an independent investigator in the field of age-related macular
degeneration (AMD). A pathologic hallmark of nonexudative AMD is the presence of drusen, lipid deposits
below the retinal pigment epithelium (RPE), which leads to RPE atrophy and photoreceptor death.
Mechanisms underlying drusen biogenesis and RPE atrophy are poorly understood, and currently there is
no therapy which slows the progression of nonexudative AMD. Long chain polyunsaturated acids (LC-
PUFAs) have been implicated in AMD pathogenesis through biochemical and epidemiology studies;
however the molecular mechanisms by which PUFAs contribute to AMD is poorly understood. Our
preliminary data suggests that ELOVL2, a key enzyme in elongation of LC-PUFAs, plays a key role in
drusen biogenesis. Our central hypothesis is that ELOVL2 activity in the retinal pigment epithelium
prevents drusen-like deposit formation, and that omega-3 products of ELOVL2 elongation are responsible
for this effect. We will test this hypothesis through the following specific aims: 1) Characterization of
metabolic and molecular changes in RPE lacking ELOVL2 enzymatic activity 2) Determine the extent that
ELOVL2 expression in the RPE is required for drusen-like deposit formation through cell specific rescue
experiments in vivo, and 3) Dissect the roles of omega-3 and omega-6 products of ELOVL2 elongation
through lipid supplementation in ELOVL2 mutant animals. Our proposed studies are significant because
they characterize a novel gene and pathway in drusen formation. The positive translational impact is the
potential development of novel therapeutic strategies for treatment of nonexudative AMD. To achieve this,
Dr. Chao has assembled an exceptional mentoring team at UCSD consisting of Dr. Jonathan Lin, M.D.,
Ph.D. an expert in retinal degenerative diseases, and Dr. Dorota Skowronska-Krawczyk, PhD, an expert on
molecular mechanisms of aging in eye diseases. This is complemented by an external clinician-scientist
committee with experience in macular degeneration research and clinician-scientist career development.
Key components of this training plan include 1) acquisition of scientific and technical expertise to use the
mouse model to study drusen biogenesis 2) formal didactic courses in grant writing, mouse genetics, and
lipid biology 3) generation of preliminary data for an R01 submission, and 4) planned transition to
independence through mentorship. This work takes place within the outstanding scientific environment and
world class facilities at UCSD and the department of ophthalmology, which has a strong track record of
producing successful clinician-scientists. Combined with his training in clinical training in vitreoretinal
surgery, this training plan will allow Dr. Chao to become a leading clinician-scientist with an independent
R01- funded research pro...

## Key facts

- **NIH application ID:** 9998955
- **Project number:** 5K08EY030510-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** DANIEL L CHAO
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $241,085
- **Award type:** 5
- **Project period:** 2019-09-01 → 2020-11-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998955

## Citation

> US National Institutes of Health, RePORTER application 9998955, Dissecting the role of ELOVL2 in Drusen Biogenesis and Age Related Macular Degeneration (5K08EY030510-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9998955. Licensed CC0.

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