# BLR&D Research Career Scientist Award

> **NIH VA IK6** · LOUIS STOKES CLEVELAND VA MEDICAL CENTER · 2024 · —

## Abstract

The Peachey lab is focused on the outer retina, to understand the biology that underlies the initial stages
of the visual process and to identify genetic mutations associated with visual disorders. The first research
area combines the power of mouse genetics with electrophysiological, anatomical and biochemical assays.
Transgenic, systemic knockout and conditional knockout models allow the expression of a target to be
manipulated and the effect of that manipulation evaluated. Some projects conducted during the most
recent RCS award (2015-date) are highlighted here: (A) To better understand the rod and cone visual
cycles by which photoreceptors regain sensitivity following bright light exposure the CDA-2 program of
Philip Kiser utilizes pharmacological blockade of known visual cycle components (e.g., RPE65) in mouse
mutants lacking proteins such as DES1 that have been proposed as playing key roles. (B) To clarify the
metabolic processes that support photoreceptor function, a recent VA Merit Review supported studies of
mice lacking the ability to transport glucose (by targeting GLUT1) or lactate (by targeting basigin) across
cell membranes of rods, cones and the retinal pigment epithelium (RPE). (C) To understand the role of
retinoschisin (RS1) we worked with a panel of Rs1 mutants to clarify the disease phenotype. Based on the
severe phenotype, a new R01 focuses on the earliest stages of development in the mouse models and uses
psychophysical assays to determine whether RS1 mutations result in incomplete photoreceptor
development. (D) Forward genetics is used to develop new mouse models for vision research, in work
supported by a subcontract to Jackson Laboratory. We collaborate through design of ocular screens, gene
mapping and defining the retinal phenotype. To date, this collaboration has developed >20 mutants
involving almost as many genes. Notably this collaboration has led to the identification of two human
disease genes, including CTNNA1 during the most recent RCS award.
 The Peachey lab has a long-standing interest in defining the genetic risk profile for age-related
macular degeneration (AMD). This began as a Merit Review in the early 2000’s focused on candidate
genes, an effort that developed into our serving as a site within the International Age-Related Macular
Degeneration Genetics Consortium (IAMDGC). During the most recent RCS award, the IAMDGC
published the most comprehensive assessment of AMD genetics to date. With the advent of the VA
Million Veteran Program (MVP), during the most recent RCS award we submitted a successful
application to conduct the first multi-ethnic analysis of AMD genetics. After defining an accurate ICD-
code based algorithm to identify AMD Cases and Controls without AMD, in the absence of gold-standard
ocular imaging results, we conducted genome wide association studies (GWAS) in MVP for European-
American (EA), African-American (AA) and Hispanic-American (HA) Veterans. The EA GWAS
replicated and extended th...

## Key facts

- **NIH application ID:** 10881652
- **Project number:** 5IK6BX005233-05
- **Recipient organization:** LOUIS STOKES CLEVELAND VA MEDICAL CENTER
- **Principal Investigator:** NEAL S. PEACHEY
- **Activity code:** IK6 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10881652

## Citation

> US National Institutes of Health, RePORTER application 10881652, BLR&D Research Career Scientist Award (5IK6BX005233-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10881652. Licensed CC0.

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