Thursday, November 20, 2025 11/20/2025

Genetic Modifiers of Retinal Disease

Award Number: R01EY027305
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2027

Group Awards By:

View Award Description

Genetic Modifiers of Retinal Disease - PROJECT SUMMARY/ABSTRACT Heritable retinal disorders, for which effective treatments are generally unavailable, contributes to the 1.02 million adults who are blind in the US. Among children, the heritable disease - Leber Congenital Amaurosis, accounts for 20% of blindness, and 10-15%of those are caused by mutations in the CRB1 gene. In addition to LCA, CRB1 mutations can also cause congenital or early-onset retinitis pigmentosa (RP), a more slowly progressive disease. CRB1 RP variants are sometimes associated with unique disease features, such as retinal telangiectasia with or without exudative retinal detachment (Coat's disease), a loss of RPE pigmentation except near arterioles (preservation of para-arteriolar RPE or PPRPE), pigment paravenous chorioretinal atrophy, cone-rod dystrophy, nanophthalmos with optic disc drusen, retinoschisis, cystoid macular edema, and macular dystrophic disease. The cause of the wide range of disease phenotypes associated with CRB1 mutations is not fully understood. Genotype-phenotype correlations that could explain the disease spectrum have not been detected among patients bearing CRB1 mutations, suggesting that environmental factors or genetic background modifiers contribute to the variability in the disease phenotypes observed. Another potential contributor to the phenotypic variability in disease presentation are Crb1 isoforms which have recently been shown to have spatially and temporally distinct expression patterns. Clearly, understanding the reasons for the variability and the mechanisms underlying the observed pathologies is extremely important for developing effective therapies. In this proposal, we will test the hypothesis that pathological changes due to Crb1 mutations depend upon the isoform affected and the genetic background on which it occurs, and their potential interactions. We will identify the molecular basis of genetic modifiers that enhance or suppress Crb1rd8 associated disease phenotypes or are epistatic upon Crb1rd8. Through the use of mouse models with isoform specific knockout alleles and controlled genetic backgrounds, we will determine their contribution to disease variability and the mechanisms through which they function. These studies address a critical unmet need for acquiring the basic biological knowledge necessary to develop 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 to further our understanding of the genetic underpinnings of disease and as a resource to examine tissue pathology, and to perform pre-clinical therapeutic tests that cannot be readily conducted in humans.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $616,564 )
2025	2025	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	000	8	3/13/2025	NON-COMPETING CONTINUATION	$616,564
														Subtotal = $616,564

Issue Date FY: 2024 ( Subtotal = $616,564 )
2024	2024	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	000	7	3/1/2024	NON-COMPETING CONTINUATION	$616,564
														Subtotal = $616,564

Issue Date FY: 2023 ( Subtotal = $602,978 )
2023	2023	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	000	6	3/13/2023	NON-COMPETING CONTINUATION	$602,978
														Subtotal = $602,978

Issue Date FY: 2022 ( Subtotal = $602,978 )
2022	2022	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	004	5	9/14/2022	COMPETING CONTINUATION	$1,652
2022	2022	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	002	5	9/13/2022	COMPETING CONTINUATION	$10,798
2022	2022	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	001	5	2/16/2022	COMPETING CONTINUATION	$592,180
2022	2020	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	000	4	2/10/2022	NON-COMPETING CONTINUATION	$0
2022	2020	JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	003	4	9/14/2022	NON-COMPETING CONTINUATION	-$1,652
														Subtotal = $602,978

Issue Date FY: 2020 ( Subtotal = $544,593 )
2020	2020	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	000	4	6/25/2020	NON-COMPETING CONTINUATION	$544,593
														Subtotal = $544,593

Issue Date FY: 2019 ( Subtotal = $544,593 )
2019	2019	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	000	3	6/27/2019	NON-COMPETING CONTINUATION	$544,593
														Subtotal = $544,593

Issue Date FY: 2018 ( Subtotal = $520,566 )
2018	2018	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	000	2	6/28/2018	NON-COMPETING CONTINUATION	$520,566
														Subtotal = $520,566

Issue Date FY: 2017 ( Subtotal = $520,566 )
2017	2017	THE JACKSON LABORATORY	600 MAIN ST	BAR HARBOR	ME	04609	HANCOCK	USA	Vision Research	000	1	8/22/2017	NEW	$520,566
														Subtotal = $520,566

Grand Total All Awards = $4,569,402

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Genetic Modifiers of Retinal Disease

Award Number: R01EY027305

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer