# Role of ARMS2 mutations in age-related macular degeneration

> **NIH NIH R01** · JACKSON LABORATORY · 2024 · $722,861

## Abstract

PROJECT SUMMARY/ABSTRACT
Genome-wide association (GWA) and linkage studies have identified >50 genes significantly associated with
age related macular degeneration (AMD). However, many questions remain. Namely, are the identified GWA
hits disease-causing variants or are they simply closely linked markers? And if the GWA hits are disease-causing
variants, how do disruptions in these molecules lead to the observed pathologies? Further, since AMD is
multifactorial, to what extent do particular combinations of factors precipitate AMD disease phenotypes or
increase disease severity, as has been suggested to be the case in large scale GWA studies, where CFH and
ARMS2/HTRA1 (locus on Chr. 10q26) appear to have synergistic effects on disease risk. Together they explain
>50% of the genetic variability observed in AMD. Furthermore, since ARMS2 and HTRA1 are in strong linkage
disequilibrium, it has been difficult to decipher whether either or both genes contribute to AMD-pathologies.
 The issues raised above can be addressed, in part, with appropriate animal models. Although mice do not
have a macula per se, they faithfully recapitulate many aspects of retinal degenerative diseases and have been
used to learn how disruption of certain molecules lead to AMD-like pathologies. In this application, we will seek
in vivo confirmation of the cell-type and subcellular localization of ARMS2, and establish whether mice bearing
the ARMS2A69S allele independently develop AMD-like sub-phenotypes and explore potential molecular
mechanisms underlying the changes. Finally, because AMD is a multifactorial disease, we will examine if AMD-
associated risk factors such as such as diet or genetic variants, such as CFH risk alleles, can potentiate AMD-
like disease phenotypes.
 Identifying the pathogenic pathways and mechanisms underlying the disease sub-phenotypes, the goal of
this proposal, is critical for developing effective therapies that can target the pre-symptomatic stage to prevent,
delay onset or decrease severity of the disease. Animal models serve an important and unique role for furthering
our understanding of the genetic underpinnings of disease, and as a resource to examine tissue pathology and
to test therapeutics that cannot be readily done in humans.

## Key facts

- **NIH application ID:** 10881394
- **Project number:** 1R01EY035397-01A1
- **Recipient organization:** JACKSON LABORATORY
- **Principal Investigator:** Patsy M Nishina
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $722,861
- **Award type:** 1
- **Project period:** 2024-06-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881394

## Citation

> US National Institutes of Health, RePORTER application 10881394, Role of ARMS2 mutations in age-related macular degeneration (1R01EY035397-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10881394. Licensed CC0.

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